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Sample records for adequate bp control

  1. SY 07-3 WHICH BP LEVELS ARE ADEQUATE TARGETS FOR THE MANAGEMENT OF DIABETIC HYPERTENSIVE PATIENTS IN ASIA?

    PubMed

    Eguchi, Kazuo

    2016-09-01

    In patients with type 2 diabetes, prevention of future cardiovascular disease is an ultimate goal in the management. Coexistence of diabetes and hypertension enhances cardiovascular risk, and antihypertensive therapy has been shown to be very effective method in reducing micro- and macrovascular complications of type 2 diabetes. However, the optimal target BP levels are still under debate. Most of the international guidelines have raised the target clinic BP from 130/80 mmHg to 140/90 mmHg, but the Japanese Society of Hypertension 2014 guideline kept the target BP level as below 130/80 mmHg. However, individualized BP-lowering treatment should be considered in patients with type 2 diabetes: in high-risk individuals such as those with a history of stroke or retinopathy, aggressive antihypertensive therapy targeting below 130 mmHg should be applied even when the initial SBP level is <140 mmHg. Recently, we performed studies concerning the BP target levels of clinic and home BP in patients with type 2 diabetes. In this session, we will show the preliminary results of these target levels and discuss how we should manage hypertension in patients with type 2 diabetes. PMID:27642961

  2. Percentage of Adults with High Blood Pressure Whose Hypertension Is Adequately Controlled

    MedlinePlus

    ... is Adequately Controlled Percentage of Adults with High Blood Pressure Whose Hypertension is Adequately Controlled Heart disease ... Survey. Age Group Percentage of People with High Blood Pressure that is Controlled by Age Group f94q- ...

  3. Percentage of Adults with High Cholesterol Whose LDL Cholesterol Levels Are Adequately Controlled

    MedlinePlus

    ... of Adults with High Cholesterol Whose LDL Cholesterol Levels are Adequately Controlled High cholesterol can double a ... with High Cholesterol that is Controlled by Education Level 8k4c-k22f Download these data » Click on legends ...

  4. 40 CFR 141.522 - How does the State determine whether my system's watershed control requirements are adequate?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... my system's watershed control requirements are adequate? 141.522 Section 141.522 Protection of... Additional Watershed Control Requirements for Unfiltered Systems § 141.522 How does the State determine whether my system's watershed control requirements are adequate? During an onsite inspection...

  5. 40 CFR 141.522 - How does the State determine whether my system's watershed control requirements are adequate?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... my system's watershed control requirements are adequate? 141.522 Section 141.522 Protection of... Additional Watershed Control Requirements for Unfiltered Systems § 141.522 How does the State determine whether my system's watershed control requirements are adequate? During an onsite inspection...

  6. 40 CFR 141.522 - How does the State determine whether my system's watershed control requirements are adequate?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... my system's watershed control requirements are adequate? 141.522 Section 141.522 Protection of... Additional Watershed Control Requirements for Unfiltered Systems § 141.522 How does the State determine whether my system's watershed control requirements are adequate? During an onsite inspection...

  7. Mutation particle swarm optimization of the BP-PID controller for piezoelectric ceramics

    NASA Astrophysics Data System (ADS)

    Zheng, Huaqing; Jiang, Minlan

    2016-01-01

    PID control is the most common used method in industrial control because its structure is simple and it is easy to implement. PID controller has good control effect, now it has been widely used. However, PID method has a few limitations. The overshoot of the PID controller is very big. The adjustment time is long. When the parameters of controlled plant are changing over time, the parameters of controller could hardly change automatically to adjust to changing environment. Thus, it can't meet the demand of control quality in the process of controlling piezoelectric ceramic. In order to effectively control the piezoelectric ceramic and improve the control accuracy, this paper replaced the learning algorithm of the BP with the mutation particle swarm optimization algorithm(MPSO) on the process of the parameters setting of BP-PID. That designed a better self-adaptive controller which is combing the BP neural network based on mutation particle swarm optimization with the conventional PID control theory. This combination is called the MPSO-BP-PID. In the mechanism of the MPSO, the mutation operation is carried out with the fitness variance and the global best fitness value as the standard. That can overcome the precocious of the PSO and strengthen its global search ability. As a result, the MPSO-BP-PID can complete controlling the controlled plant with higher speed and accuracy. Therefore, the MPSO-BP-PID is applied to the piezoelectric ceramic. It can effectively overcome the hysteresis, nonlinearity of the piezoelectric ceramic. In the experiment, compared with BP-PID and PSO-BP-PID, it proved that MPSO is effective and the MPSO-BP-PID has stronger adaptability and robustness.

  8. Sodium nitroprusside: low price and safe drug to control BP during thrombolysis in AIS.

    PubMed

    Koslyk, Jessyca L; Ducci, Renata D; Nóvak, Edison M; Zétola, Viviane F; Lange, Marcos C

    2015-09-01

    This study analyzes the use of sodium nitroprusside (SN) as an option to reduce blood pressure (BP) below 180/105 mmHg during the management of acute ischemic stroke (AIS) in patients submitted to intravenous thrombolysis.Method The sample was composed by 60 patients who had AIS and were submitted to intravenous rtPA, split in two groups: half in the control group (CG) with BP < 180/105 mmHg and half in SN group with BP > 180/105 mmHg. Outcome variables were any hemorrhagic transformation (HT); the presence of symptomatic HT, National Institute of Health Stroke Scale (NIHSS) after 24 hours of treatment; the independence on discharge and death until three months after stroke onset.Results There were no statistical differences between both groups to any of the outcome variables analyzed.Conclusion The SN might be safe for BP control during thrombolysis to AIS. PMID:26352493

  9. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... permits a valid comparison with a control to provide a quantitative assessment of drug effect. The... data analyses performed. (c) The Director of the Center for Drug Evaluation and Research may, on...

  10. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... permits a valid comparison with a control to provide a quantitative assessment of drug effect. The... data analyses performed. (c) The Director of the Center for Drug Evaluation and Research may, on...

  11. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... permits a valid comparison with a control to provide a quantitative assessment of drug effect. The... data analyses performed. (c) The Director of the Center for Drug Evaluation and Research may, on...

  12. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... permits a valid comparison with a control to provide a quantitative assessment of drug effect. The... data analyses performed. (c) The Director of the Center for Drug Evaluation and Research may, on...

  13. Translation control during prolonged mTORC1 inhibition mediated by 4E-BP3

    PubMed Central

    Tsukumo, Yoshinori; Alain, Tommy; Fonseca, Bruno D.; Nadon, Robert; Sonenberg, Nahum

    2016-01-01

    Targeting mTORC1 is a highly promising strategy in cancer therapy. Suppression of mTORC1 activity leads to rapid dephosphorylation of eIF4E-binding proteins (4E-BP1–3) and subsequent inhibition of mRNA translation. However, how the different 4E-BPs affect translation during prolonged use of mTOR inhibitors is not known. Here we show that the expression of 4E-BP3, but not that of 4E-BP1 or 4E-BP2, is transcriptionally induced during prolonged mTORC1 inhibition in vitro and in vivo. Mechanistically, our data reveal that 4E-BP3 expression is controlled by the transcription factor TFE3 through a cis-regulatory element in the EIF4EBP3 gene promoter. CRISPR/Cas9-mediated EIF4EBP3 gene disruption in human cancer cells mitigated the inhibition of translation and proliferation caused by prolonged treatment with mTOR inhibitors. Our findings show that 4E-BP3 is an important effector of mTORC1 and a robust predictive biomarker of therapeutic response to prolonged treatment with mTOR-targeting drugs in cancer. PMID:27319316

  14. RanBP3 Regulates Melanoma Cell Proliferation via Selective Control of Nuclear Export.

    PubMed

    Pathria, Gaurav; Garg, Bhavuk; Wagner, Christine; Garg, Kanika; Gschaider, Melanie; Jalili, Ahmad; Wagner, Stephan N

    2016-01-01

    Chromosome region maintenance 1-mediated nucleocytoplasmic transport has been shown as a potential anticancer target in various malignancies. However, the role of the most characterized chromosome region maintenance 1 cofactor ran binding protein 3 (RanBP3) in cancer cell biology has never been investigated. Utilizing a loss-of-function experimental setting in a vast collection of genetically varied melanoma cell lines, we observed the requirement of RanBP3 in melanoma cell proliferation and survival. Mechanistically, we suggest the reinstatement of transforming growth factor-β (TGF-β)-Smad2/3-p21(Cip1) tumor-suppressor axis as part of the RanBP3 silencing-associated antiproliferative program. Employing extensive nuclear export sequence analyses and immunofluorescence-based protein localization studies, we further present evidence suggesting the requirement of RanBP3 function for the nuclear exit of the weak nuclear export sequence-harboring extracellular signal-regulated kinase protein, although it is dispensable for general CRM1-mediated nuclear export of strong nuclear export sequence-harboring cargoes. Rendering mechanistic support to RanBP3 silencing-mediated apoptosis, consequent to extracellular signal-regulated kinase nuclear entrapment, we observed increased levels of cytoplasmically restricted nonphosphorylated/active proapoptotic Bcl-2-antagonist of cell death (BAD) protein. Last, we present evidence suggesting the frequently activated mitogen-activated protein kinase signaling in melanoma as a potential founding basis for a deregulated post-translational control of RanBP3 activity. Collectively, the presented data suggest RanBP3 as a potential target for therapeutic intervention in human melanoma.

  15. Local renal circadian clocks control fluid-electrolyte homeostasis and BP.

    PubMed

    Tokonami, Natsuko; Mordasini, David; Pradervand, Sylvain; Centeno, Gabriel; Jouffe, Céline; Maillard, Marc; Bonny, Olivier; Gachon, Frédéric; Gomez, R Ariel; Sequeira-Lopez, Maria Luisa S; Firsov, Dmitri

    2014-07-01

    The circadian timing system is critically involved in the maintenance of fluid and electrolyte balance and BP control. However, the role of peripheral circadian clocks in these homeostatic mechanisms remains unknown. We addressed this question in a mouse model carrying a conditional allele of the circadian clock gene Bmal1 and expressing Cre recombinase under the endogenous Renin promoter (Bmal1(lox/lox)/Ren1(d)Cre mice). Analysis of Bmal1(lox/lox)/Ren1(d)Cre mice showed that the floxed Bmal1 allele was excised in the kidney. In the kidney, BMAL1 protein expression was absent in the renin-secreting granular cells of the juxtaglomerular apparatus and the collecting duct. A partial reduction of BMAL1 expression was observed in the medullary thick ascending limb. Functional analyses showed that Bmal1(lox/lox)/Ren1(d)Cre mice exhibited multiple abnormalities, including increased urine volume, changes in the circadian rhythm of urinary sodium excretion, increased GFR, and significantly reduced plasma aldosterone levels. These changes were accompanied by a reduction in BP. These results show that local renal circadian clocks control body fluid and BP homeostasis. PMID:24652800

  16. 40 CFR 141.522 - How does the State determine whether my system's watershed control requirements are adequate?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection-Systems Serving Fewer Than 10,000 People... is adequate to limit potential contamination by Cryptosporidium oocysts. The adequacy of the...

  17. 40 CFR 141.522 - How does the State determine whether my system's watershed control requirements are adequate?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection-Systems Serving Fewer Than 10,000 People... is adequate to limit potential contamination by Cryptosporidium oocysts. The adequacy of the...

  18. JS ISH-ISN-3 OPTIMAL TARGETS FOR BP CONTROL IN CKD.

    PubMed

    Wheeler, David

    2016-09-01

    Hypertension is the most prevalent complication of chronic kidney disease (CKD). Lowering high blood pressure slows progressive loss of kidney function and may also reduce the associated risk of cardiovascular complications, a common cause of premature death in CKD patients.Current International Guidelines produced by Kidney Disease: Improving Global Outcomes (KDIGO) acknowledges that no single BP target is optimal for all CKD patients, and encourages individualization of treatment depending on age, the severity of albuminuria and comorbidities. When published in 2012, the available evidence indicated that in CKD patients without albuminuria, the target BP should be ≤140 mmHg systolic and ≤90 mmHg diastolic. However, in most patients with an albumin excretion rate of ≥30 mg/24 h (i.e., those with both micro- and macroalbuminuria), a lower target of ≤130 mmHg systolic and ≤80 mmHg diastolic was suggested. In achieving BP control, the value of lifestyle changes and the need for multiple pharmacological agents was acknowledged. Use of agents that block the renin-angiotensin-aldosterone system was recommended or suggested in all patients with an albumin excretion rate of ≥30 mg/24 h. Recommendations are almost identical in CKD patients with and without diabetes.Recent data from SPRINT (which included CKD patients) and other clinical trials has led nephrologists to ask whether targets lower than those recommend by KDIGO are appropriate and the guidelines are currently undergoing an update. Controversies remain around discontinuation of ACE/ARB in patients with stage 4-5 CKD and dual renin-angiotensin-aldosterone system blockade. PMID:27642915

  19. Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo

    PubMed Central

    Ivanova, Daniela; Dirks, Anika; Montenegro-Venegas, Carolina; Schöne, Cornelia; Altrock, Wilko D; Marini, Claudia; Frischknecht, Renato; Schanze, Denny; Zenker, Martin; Gundelfinger, Eckart D; Fejtova, Anna

    2015-01-01

    Persistent experience-driven adaptation of brain function is associated with alterations in gene expression patterns, resulting in structural and functional neuronal remodeling. How synaptic activity—in particular presynaptic performance—is coupled to gene expression in nucleus remains incompletely understood. Here, we report on a role of CtBP1, a transcriptional co-repressor enriched in presynapses and nuclei, in the activity-driven reconfiguration of gene expression in neurons. We demonstrate that presynaptic and nuclear pools of CtBP1 are interconnected and that both synaptic retention and shuttling of CtBP1 between cytoplasm and nucleus are co-regulated by neuronal activity. Finally, we show that CtBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins Bassoon and Piccolo. This association is regulated by neuronal activity via modulation of cellular NAD/NADH levels and restrains the size of the CtBP1 pool available for nuclear import, thus contributing to the control of activity-dependent gene expression. Our combined results reveal a mechanism for coupling activity-induced molecular rearrangements in the presynapse with reconfiguration of neuronal gene expression. PMID:25652077

  20. Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo.

    PubMed

    Ivanova, Daniela; Dirks, Anika; Montenegro-Venegas, Carolina; Schöne, Cornelia; Altrock, Wilko D; Marini, Claudia; Frischknecht, Renato; Schanze, Denny; Zenker, Martin; Gundelfinger, Eckart D; Fejtova, Anna

    2015-04-15

    Persistent experience-driven adaptation of brain function is associated with alterations in gene expression patterns, resulting in structural and functional neuronal remodeling. How synaptic activity-in particular presynaptic performance-is coupled to gene expression in nucleus remains incompletely understood. Here, we report on a role of CtBP1, a transcriptional co-repressor enriched in presynapses and nuclei, in the activity-driven reconfiguration of gene expression in neurons. We demonstrate that presynaptic and nuclear pools of CtBP1 are interconnected and that both synaptic retention and shuttling of CtBP1 between cytoplasm and nucleus are co-regulated by neuronal activity. Finally, we show that CtBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins Bassoon and Piccolo. This association is regulated by neuronal activity via modulation of cellular NAD/NADH levels and restrains the size of the CtBP1 pool available for nuclear import, thus contributing to the control of activity-dependent gene expression. Our combined results reveal a mechanism for coupling activity-induced molecular rearrangements in the presynapse with reconfiguration of neuronal gene expression.

  1. Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3

    PubMed Central

    Amstutz, Beat; Gastaldelli, Michele; Kälin, Stefan; Imelli, Nicola; Boucke, Karin; Wandeler, Eliane; Mercer, Jason; Hemmi, Silvio; Greber, Urs F

    2008-01-01

    Endocytosis supports cell communication, growth, and pathogen infection. The species B human adenovirus serotype 3 (Ad3) is associated with epidemic conjunctivitis, and fatal respiratory and systemic disease. Here we show that Ad3 uses dynamin-independent endocytosis for rapid infectious entry into epithelial and haematopoietic cells. Unlike Ad5, which uses dynamin-dependent endocytosis, Ad3 endocytosis spatially and temporally coincided with enhanced fluid-phase uptake. It was sensitive to macropinocytosis inhibitors targeting F-actin, protein kinase C, the sodium–proton exchanger, and Rac1 but not Cdc42. Infectious Ad3 macropinocytosis required viral activation of p21-activated kinase 1 (PAK1) and the C-terminal binding protein 1 of E1A (CtBP1), recruited to macropinosomes. These macropinosomes also contained the Ad3 receptors CD46 and αv integrins. CtBP1 is a phosphorylation target of PAK1, and is bifunctionally involved in membrane traffic and transcriptional repression of cell cycle, cancer, and innate immunity pathways. Phosphorylation-defective S147A-CtBP1 blocked Ad3 but not Ad5 infection, providing a direct link between PAK1 and CtBP1. The data show that viruses induce macropinocytosis for infectious entry, a pathway used in antigen presentation and cell migration. PMID:18323776

  2. Personal and Familial Correlates of Bipolar (BP)-I Disorder in Children with a Diagnosis of BP-I Disorder with a Positive Child Behavior Checklist (CBCL)-Severe Dysregulation Profile: A Controlled Study

    PubMed Central

    Biederman, Joseph; Martelon, MaryKate; Faraone, Stephen V.; Woodworth, Yvonne; Spencer, Thomas J.; Wozniak, Janet

    2012-01-01

    Background Although the DSM-IV provides explicit criteria for the diagnosis of BP-I disorder, this is a complex diagnosis that requires high levels of clinical expertise. Previous work shows children with a unique profile of the CBCL of high scores (2SD) on the Attention Problems (AP), Aggressive Behavior (AGG), and Anxious-Depressed (AD) (A-A-A) subscales are more likely than other children to meet criteria for BP-I disorder in both epidemiological and clinical samples. However, since not all BP-I disorder children have a positive profile questions remain as to its informativeness, particularly in the absence of an expert diagnostician. Methods Analyses were conducted comparing personal and familial correlates of BP-I disorder in 140 youth with a structured interview and an expert clinician based DSM-IV diagnosis of BP-I disorder with (N=80) and without (N=60) a positive CBCL- Severe Dysregulation profile, and 129 controls of similar age and sex without ADHD or a mood disorder. Subjects were comprehensively assessed with structured diagnostic interviews and wide range of functional measures. We defined the CBCL-Severe Dysregulation profile as an aggregate cut-off score of ≥210 on the A-A-A scales. Results BP-I probands with and without a positive CBCL-Severe Dysregulation profile significantly differed from Controls in patterns of psychiatric comorbidity, psychosocial and psychoeducational dysfunction, and cognitive deficits, as well as in their risk for BP-I disorder in first degree relatives. Limitations Because the sample was referred and largely Caucasian, findings may not generalize to community samples and other ethnic groups. Conclusion A positive CBCL-Severe Dysregulation profile identifies a severe subgroup of BP-I disorder youth. PMID:23164462

  3. Is a diagnostic system based exclusively on agar gel immunodiffusion adequate for controlling the spread of equine infectious anaemia?

    PubMed

    Scicluna, Maria Teresa; Issel, Charles J; Cook, Frank R; Manna, Giuseppe; Cersini, Antonella; Rosone, Francesca; Frontoso, Raffaele; Caprioli, Andrea; Antognetti, Valeria; Antonetti, Valeria; Autorino, Gian Luca

    2013-07-26

    To improve the efficiency of the National equine infectious anaemia (EIA) surveillance program in Italy, a three-tiered diagnostic system has been adopted. This procedure involves initial screening by ELISA (Tier 1) with test-positive samples confirmed by the agar gel immunodiffusion test (AGIDT) (Tier 2) and, in the case of ELISA positive/AGIDT negative results, final determination by immunoblot (IB) (Tier 3). During this evaluation, 74,880 samples, principally collected from two Regions of Central Italy (Latium and Abruzzo) were examined, with 44 identified as negative in AGIDT but positive in both ELISA and IB. As the majority of these reactions occurred in mules, an observational study was conducted in this hybrid equid species to investigate if there is a correlation between plasma-associated viral loads and serological reactivity, to test the hypothesis that false-negative or very weak positive AGIDT results are associated with elite control of EIA virus (EIAV) replication accompanied by reduced transmission risks. The study animals consisted of 5 mules with positive AGIDT readings, along with another 5 giving negative or very weak positive results in this test. All mules were seropositive in Elisa and IB. Samples were collected routinely during an initial 56-day observation period, prior to dexamethasone treatment lasting 10 days, to determine the effect of immune suppression (IS) on clinical, humoral and virological responses. All mules were monitored for a further 28 days from day 0 of IS. None of the animals experienced relevant clinical responses before IS and there were no significant changes in antibody levels in ELISA, IB or AGIDT. However, plasma-associated viral-RNA (vRNA) loads, as determined using TaqMan(®) based RT-PCR, showed unexpectedly high sample to sample variation in all mules, demonstrating host-mediated control of viral replication is not constant over time. Furthermore, there was no apparent correlation between vRNA loads and antibody

  4. Does 24bp Duplication of Human CHIT1 Gene (Chitotriosidase1) Predispose to Filarial Chyluria? A Case-Control Study

    PubMed Central

    Pant, Shriya; Agarwal, Jyotsna; Gangwar, Pravin K; Waseem, Mohammad; Gupta, Prashant; Sankhwar, Satya N; Purkait, Bimalesh

    2016-01-01

    Introduction Chyluria which is endemic in many parts of the world is mainly caused by Wuchereria bancrofti. CHIT1 (chitotriosidase) is produced by macrophages and plays an important role in the defense against chitin containing pathogen such as filarial parasite. Variation in the coding region with 24 bp duplication allele results in reduced CHIT1 activity that enhance the survival of parasite which may play a role in the occurrence of disease. Aim To examine the role of 24bp duplication of CHIT1 gene in patients of filarial chyluria (FC). Materials and Methods A case-control study was carried out where 155 confirmed FC patients and equal number of age-, sex- and residence-matched controls without any symptoms or signs of lymphatic filariasis, confirmed by negative immunochromatographic card test (ICT) and IgG/IgM combo rapid antibody test, from a hospital-based population were enrolled. Filarial aetiology was confirmed on the basis of DEC-provocative test (Giemsa staining), ICT and IgG/IgM- antifiarial antibody test. The patients positive by either of these tests were enrolled as FC cases. 24bp duplication in CHIT1 gene in FC was detected by the product size 99bp of amplified gene using polymerase chain reaction. Results The mean ages of patients and controls were 38.25±12.09 and 35.45±12.53 years, respectively while male: female ratio was 2.4:1. The mean duration of illness in chyluria patients was 62.81±60.83 months and mean number of episodes was 2.54±1.11. Homozygous wild type, heterozygous and homozygous mutant frequencies were 10.3%, 81.3% and 8.4% in FC patients and 18.7%, 75.5%, and 5.8% in controls, respectively. The 24bp duplication in CHIT1 gene showed a significant association in Heterozygous (HT) genotype with Odd Ratio (OR) of 1.95, 95% Confidence Interval (CI) (1.01-3.77); p=0.04. However, the homozygous mutant genotype (TT) was found to be non-significant with OR of 2.61, 95% CI (0.91-7.45); p=0.07. The combination of both HT+TT was also found

  5. 21 CFR 1404.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adequate evidence. 1404.900 Section 1404.900 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 1404.900 Adequate evidence. Adequate evidence means information sufficient...

  6. Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis

    PubMed Central

    Gardner, Thomas W.; Abcouwer, Steven F.; Losiewicz, Mandy K.

    2015-01-01

    Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1. PMID:26199279

  7. Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic regulation of retinal protein synthesis.

    PubMed

    Gardner, Thomas W; Abcouwer, Steven F; Losiewicz, Mandy K; Fort, Patrice E

    2015-09-15

    Control of protein synthesis in insulin-responsive tissues has been well characterized, but relatively little is known about how this process is regulated in nervous tissues. The retina exhibits a relatively high protein synthesis rate, coinciding with high basal Akt and metabolic activities, with the majority of retinal ATP being derived from aerobic glycolysis. We examined the dependency of retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but did not affect glycolytic lactate production. Surprisingly, the glycolytic inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG) on retinal protein synthesis correlated with inhibition of lactate production and diminished ATP content, with all these effects reversed by provision of d-mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or eIF2α phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1. 2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce mTORC1 activity, as indicated by unaltered raptor-associated mTOR autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium. Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1. These results demonstrate a novel mechanism regulating protein synthesis in the retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E-BP1.

  8. Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery.

    PubMed

    Mahoney, Rebekah Elizabeth; Azpurua, Jorge; Eaton, Benjamin A

    2016-01-01

    Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell autonomous insulin signaling within the Drosophila CM9 motor neuron regulates the release of neurotransmitter via alteration of the synaptic vesicle fusion machinery. This effect of insulin utilizes the FOXO-dependent regulation of the thor gene, which encodes the Drosophila homologue of the eif-4e binding protein (4eBP). A critical target of this regulatory mechanism is Complexin, a synaptic protein known to regulate synaptic vesicle exocytosis. We find that the amounts of Complexin protein observed at the synapse is regulated by insulin and genetic manipulations of Complexin levels support the model that increased synaptic Complexin reduces neurotransmission in response to insulin signaling. PMID:27525480

  9. Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery

    PubMed Central

    Mahoney, Rebekah Elizabeth; Azpurua, Jorge; Eaton, Benjamin A

    2016-01-01

    Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell autonomous insulin signaling within the Drosophila CM9 motor neuron regulates the release of neurotransmitter via alteration of the synaptic vesicle fusion machinery. This effect of insulin utilizes the FOXO-dependent regulation of the thor gene, which encodes the Drosophila homologue of the eif-4e binding protein (4eBP). A critical target of this regulatory mechanism is Complexin, a synaptic protein known to regulate synaptic vesicle exocytosis. We find that the amounts of Complexin protein observed at the synapse is regulated by insulin and genetic manipulations of Complexin levels support the model that increased synaptic Complexin reduces neurotransmission in response to insulin signaling. DOI: http://dx.doi.org/10.7554/eLife.16807.001 PMID:27525480

  10. Adequate Wound Care and Use of Bed Nets as Protective Factors against Buruli Ulcer: Results from a Case Control Study in Cameroon

    PubMed Central

    Landier, Jordi; Boisier, Pascal; Fotso Piam, Félix; Noumen-Djeunga, Blanbin; Simé, Joseph; Wantong, Fidèle Gaetan; Marsollier, Laurent; Fontanet, Arnaud; Eyangoh, Sara

    2011-01-01

    Background Buruli ulcer is an infectious disease involving the skin, caused by Mycobacterium ulcerans. Its exact transmission mechanism remains unknown. Several arguments indicate a possible role for insects in its transmission. A previous case-control study in the Nyong valley region in central Cameroon showed an unexpected association between bed net use and protection against Buruli ulcer. We investigated whether this association persisted in a newly discovered endemic Buruli ulcer focus in Bankim, northwestern Cameroon. Methodology/Principal Findings We conducted a case-control study on 77 Buruli ulcer cases and 153 age-, gender- and village-matched controls. Participants were interviewed about their activities and habits. Multivariate conditional logistic regression analysis identified systematic use of a bed net (Odds-Ratio (OR) = 0.4, 95% Confidence Interval [95%CI] = [0.2–0.9], p-value (p) = 0.04), cleansing wounds with soap (OR [95%CI] = 0.1 [0.03–0.3], p<0.0001) and growing cassava (OR [95%CI] = 0.3 [0.2–0.7], p = 0.005) as independent protective factors. Independent risk factors were bathing in the Mbam River (OR [95%CI] = 6.9 [1.4–35], p = 0.02) and reporting scratch lesions after insect bites (OR [95%CI] = 2.7 [1.4–5.4], p = 0.004). The proportion of cases that could be prevented by systematic bed net use was 32%, and by adequate wound care was 34%. Conclusions/Significance Our study confirms that two previously identified factors, adequate wound care and bed net use, significantly decreased the risk of Buruli ulcer. These associations withstand generalization to different geographic, climatic and epidemiologic settings. Involvement of insects in the household environment, and the relationship between wound hygiene and M. ulcerans infection should now be investigated. PMID:22087346

  11. A Novel 154-bp Deletion in the Human Mitochondrial DNA Control Region in Healthy Individuals

    PubMed Central

    Behar, Doron M.; Blue-Smith, Jason; Soria-Hernanz, David F.; Tzur, Shay; Hadid, Yarin; Bormans, Concetta; Moen, Alexander; Tyler-Smith, Chris; Quintana-Murci, Lluis; Wells, R. Spencer

    2009-01-01

    The biological role of the mitochondrial DNA (mtDNA) control region in mtDNA replication remains unclear. In a worldwide survey of mtDNA variation in the general population, we have identified a novel large control region deletion spanning positions 16154 to 16307 (m.16154_16307del154). The population prevalence of this deletion is low, since it was only observed in 1 out of over 120,000 mtDNA genomes studied. The deletion is present in a nonheteroplasmic state, and was transmitted by a mother to her two sons with no apparent past or present disease conditions. The identification of this large deletion in healthy individuals challenges the current view of the control region as playing a crucial role in the regulation of mtDNA replication, and supports the existence of a more complex system of multiple or epigenetically-determined replication origins. PMID:18629826

  12. R7BP Complexes With RGS9-2 and RGS7 in the Striatum Differentially Control Motor Learning and Locomotor Responses to Cocaine

    PubMed Central

    Anderson, Garret R; Cao, Yan; Davidson, Steve; Truong, Hai V; Pravetoni, Marco; Thomas, Mark J; Wickman, Kevin; Giesler, Glenn J; Martemyanov, Kirill A

    2010-01-01

    In the striatum, signaling through G protein-coupled dopamine receptors mediates motor and reward behavior, and underlies the effects of addictive drugs. The extent of receptor responses is determined by RGS9-2/Gβ5 complexes, a striatally enriched regulator that limits the lifetime of activated G proteins. Recent studies suggest that the function of RGS9-2/Gβ5 is controlled by the association with an additional subunit, R7BP, making elucidation of its contribution to striatal signaling essential for understanding molecular mechanisms of behaviors mediated by the striatum. In this study, we report that elimination of R7BP in mice results in motor coordination deficits and greater locomotor response to morphine administration, consistent with the essential role of R7BP in maintaining RGS9-2 expression in the striatum. However, in contrast to previously reported observations with RGS9-2 knockouts, mice lacking R7BP do not show higher sensitivity to locomotor-stimulating effects of cocaine. Using a striatum-specific knockdown approach, we show that the sensitivity of motor stimulation to cocaine is instead dependent on RGS7, whose complex formation with R7BP is dictated by RGS9-2 expression. These results indicate that dopamine signaling in the striatum is controlled by concerted interplay between two RGS proteins, RGS7 and RGS9-2, which are balanced by a common subunit, R7BP. PMID:20043004

  13. Analysis of Lymphocytic DNA Damage in Early Multiple Sclerosis by Automated Gamma-H2AX and 53BP1 Foci Detection: A Case Control Study

    PubMed Central

    Rasche, Ludwig; Heiserich, Lisa; Behrens, Janina Ruth; Lenz, Klaus; Pfuhl, Catherina; Wakonig, Katharina; Gieß, René Markus; Freitag, Erik; Eberle, Caroline; Wuerfel, Jens; Dörr, Jan; Bauer, Peter; Bellmann-Strobl, Judith; Paul, Friedemann; Roggenbuck, Dirk; Ruprecht, Klemens

    2016-01-01

    Background In response to DNA double-strand breaks, the histone protein H2AX becomes phosphorylated at its C-terminal serine 139 residue, referred to as γ-H2AX. Formation of γ-H2AX foci is associated with recruitment of p53-binding protein 1 (53BP1), a regulator of the cellular response to DNA double-strand breaks. γ-H2AX expression in peripheral blood mononuclear cells (PBMCs) was recently proposed as a diagnostic and disease activity marker for multiple sclerosis (MS). Objective To evaluate the significance of γ-H2AX and 53BP1 foci in PBMCs as diagnostic and disease activity markers in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS) using automated γ-H2AX and 53BP1 foci detection. Methods Immunocytochemistry was performed on freshly isolated PBMCs of patients with CIS/early RRMS (n = 25) and healthy controls (n = 27) with γ-H2AX and 53BP1 specific antibodies. Nuclear γ-H2AX and 53BP1 foci were determined using a fully automated reading system, assessing the numbers of γ-H2AX and 53BP1 foci per total number of cells and the percentage of cells with foci. Patients underwent contrast enhanced 3 Tesla magnetic resonance imaging (MRI) and clinical examination including expanded disability status scale (EDSS) score. γ-H2AX and 53BP1 were also compared in previously frozen PBMCs of each 10 CIS/early RRMS patients with and without contrast enhancing lesions (CEL) and 10 healthy controls. Results The median (range) number of γ-H2AX (0.04 [0–0.5]) and 53BP1 (0.005 [0–0.2]) foci per cell in freshly isolated PBMCs across all study participants was low and similar to previously reported values of healthy individuals. For both, γ-H2AX and 53BP1, the cellular focus number as well as the percentage of positive cells did not differ between patients with CIS/RRMS and healthy controls. γ-H2AX and 53BP1 levels neither correlated with number nor volume of T2-weighted lesions on MRI, nor with the EDSS. Although γ-H2AX, but not

  14. mtDNA control-region sequence variation suggests multiple independent origins of an "Asian-specific" 9-bp deletion in sub-Saharan Africans.

    PubMed Central

    Soodyall, H.; Vigilant, L.; Hill, A. V.; Stoneking, M.; Jenkins, T.

    1996-01-01

    The intergenic COII/tRNA(Lys) 9-bp deletion in human mtDNA, which is found at varying frequencies in Asia, Southeast Asia, Polynesia, and the New World, was also found in 81 of 919 sub-Saharan Africans. Using mtDNA control-region sequence data from a subset of 41 individuals with the deletion, we identified 22 unique mtDNA types associated with the deletion in Africa. A comparison of the unique mtDNA types from sub-Saharan Africans and Asians with the 9-bp deletion revealed that sub-Saharan Africans and Asians have sequence profiles that differ in the locations and frequencies of variant sites. Both phylogenetic and mismatch-distribution analysis suggest that 9-bp deletion arose independently in sub-Saharan Africa and Asia and that the deletion has arisen more than once in Africa. Within Africa, the deletion was not found among Khoisan peoples and was rare to absent in western and southwestern African populations, but it did occur in Pygmy and Negroid populations from central Africa and in Malawi and southern African Bantu-speakers. The distribution of the 9-bp deletion in Africa suggests that the deletion could have arisen in central Africa and was then introduced to southern Africa via the recent "Bantu expansion." PMID:8644719

  15. Asbestos/NESHAP adequately wet guidance

    SciTech Connect

    Shafer, R.; Throwe, S.; Salgado, O.; Garlow, C.; Hoerath, E.

    1990-12-01

    The Asbestos NESHAP requires facility owners and/or operators involved in demolition and renovation activities to control emissions of particulate asbestos to the outside air because no safe concentration of airborne asbestos has ever been established. The primary method used to control asbestos emissions is to adequately wet the Asbestos Containing Material (ACM) with a wetting agent prior to, during and after demolition/renovation activities. The purpose of the document is to provide guidance to asbestos inspectors and the regulated community on how to determine if friable ACM is adequately wet as required by the Asbestos NESHAP.

  16. Genetic polymorphism in HLA-G 3'UTR 14-bp ins/del and risk of cancer: a meta-analysis of case-control study.

    PubMed

    Li, Tao; Huang, Haohai; Liao, Dan; Ling, Huahuang; Su, Bingguang; Cai, Maode

    2015-08-01

    Accumulating evidence has suggested that the human leucocyte antigen-G (HLA-G) 14 bp ins/del polymorphism might be related to cancer susceptibility. However, epidemiologic findings have been inconsistent. Therefore, we performed a meta-analysis of case-control study to derive a more precise estimation of this association. Electronic databases were searched to identify all eligible studies of HLA-G 14 bp ins/del polymorphism and cancer risk. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to evaluate the strength of the association in fixed-effects model or random-effects model according to heterogeneity. Publication bias, sensitivity analysis and subgroup analyses based on cancer type, ethnicity, source of controls and sample size were also performed. A total of 14 case-control studies, involving 2,757 cases and 3,972 controls, were included in the present meta-analysis. The pooled analysis showed that there is no significant relationship between the HLA-G 14 bp ins/del polymorphism and cancer susceptibility under the genetic models (for the allele model del vs. ins: OR 1.13, 95 % CI 1.00-1.27; for the homozygote comparison model del/del vs. ins/ins: OR 1.22, 95 % CI 0.95-1.56; for the dominant model del/del + ins/del vs. ins/ins: OR 1.15, 95 % CI 0.94-1.42; for recessive model del/del vs. ins/del + ins/ins: OR 1.13, 95 % CI 0.96-1.34; respectively). Subgroup analyses indicated significant association among breast cancer, population based control and the large sample size group in some genetic models. Our investigations demonstrate that genotypes for the HLA-G 14 bp ins/del polymorphism may be not associated with overall cancer risk. In a subgroup meta-analysis, however, HLA-G 14-bp ins/del polymorphism might contribute to breast cancer susceptibility.

  17. Toward More Adequate Quantitative Instructional Research.

    ERIC Educational Resources Information Center

    VanSickle, Ronald L.

    1986-01-01

    Sets an agenda for improving instructional research conducted with classical quantitative experimental or quasi-experimental methodology. Includes guidelines regarding the role of a social perspective, adequate conceptual and operational definition, quality instrumentation, control of threats to internal and external validity, and the use of…

  18. IGF2BP2 rs11705701 polymorphisms are associated with prediabetes in a Chinese population: A population-based case-control study

    PubMed Central

    Han, Liyuan; Li, Yuanyuan; Tang, Linlin; Chen, Zhongwei; Zhang, Tao; Chen, Sihan; Liu, Shengyuan; Peng, Xiaolin; Mai, Yifeng; Zhuo, Renjie; Wang, Changyi; Duan, Shiwei

    2016-01-01

    Associations between insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs11705701, insulin receptor substrate 1 rs7578326, gastric inhibitory polypeptide receptor rs10423928 and transcription factor 7-like 2 rs12255372 gene polymorphisms with prediabetes and type 2 diabetes (T2D) have not been evaluated in the Han Chinese population. These four genetic variants were investigated for their associations with prediabetes and T2D among 490 unrelated patients with T2D, 471 patients with prediabetes and 575 healthy controls. Sequenom MassARRAY software was used to genotype the patients for these variants. The Generalized Multifactor Dimensionality Reduction method was used to analyze the gene-gene and gene-environment interactions. A breakdown analysis by gender revealed a significant association of IGF2BP2 rs11705701 with prediabetes under the dominant genetic model in females following application of the Bonferroni correction (odds ratio = 0.26; 95% confidence interval = 0.10–0.67; P=0.005). However, no significant associations were reported between any of the other three polymorphisms and T2D under any genetic models. Furthermore, there were no statistically significant gene-gene or gene-environment interactions when evaluated with the above association tests. The present case-control study reveals a significant association between IGF2BP2 rs11705701 and prediabetes in female patients. PMID:27588103

  19. Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

    PubMed Central

    Rao, Ping; Wang, Hao; Fang, Honghong; Gao, Qing; Zhang, Jie; Song, Manshu; Zhou, Yong; Wang, Youxin; Wang, Wei

    2016-01-01

    Background: Genome-wide association studies (GWAS) found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM) risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG) (adjusted odd ratio (AOR) = 1.962, 95% confidence interval (95% CI) = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA) (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021). The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05). The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations. PMID:27294943

  20. JS ISH-ISN-2 ROLE OF THE KIDNEY IN RESISTANT HYPERTENSION: WHY SO RESISTANT TO BP CONTROL IN CKD PATIENTS?

    PubMed

    Bakris, George

    2016-09-01

    Resistant hypertension is defined as a blood pressure above 140/90 mmHg despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease (CKD) is one of the more common patient comorbidities associated with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. CKD is associated with premature vascular ageing, characterized by accelerated arteriosclerosis or atherosclerosis and endothelial dysfunction. Vascular changes appear in the early stages of CKD, although they are most pronounced in advanced stages. Systolic hypertension is the most common form of hypertension in patients with CKD, and raised systolic BP is independently associated with risk of progression to chronic kidney disease. Rigid arterial walls attenuate baroreceptor control of efferent sympathetic activity and vagal activation. Reduced baroreflex sensitivity maintains high sympathetic activity directed to the heart, blood vessels, and kidney, which contributes to high BP. Patients with CKD also have an inadequate vasoconstrictor response to baroreceptor unloading, this contributes to frequent orthostatic hypotension and circulatory instability. Moreover, hypoxemia of renal tissue due to kidney damage activates the CNS via afferent nerves, which also contributes to high sympathetic activity. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation are under investigation especially in patients with advanced chronic kidney disease. One of the most common reasons for blood pressure resistance in CKD is volume overload with increased sympathetic activity also being a major contributor. We will focus on the epidemiology as well as pathophysiology and therapeutic approaches to managing resistant hypertension in CKD stages 3

  1. 34 CFR 85.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Adequate evidence. 85.900 Section 85.900 Education Office of the Secretary, Department of Education GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 85.900 Adequate evidence. Adequate evidence means information sufficient to support...

  2. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  3. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  4. 12 CFR 380.52 - Adequate protection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Adequate protection. 380.52 Section 380.52... ORDERLY LIQUIDATION AUTHORITY Receivership Administrative Claims Process § 380.52 Adequate protection. (a... interest of a claimant, the receiver shall provide adequate protection by any of the following means:...

  5. BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase

    PubMed Central

    Larsen, Stig; Butthongkomvong, Kritiya; Manikhas, Alexey; Trishkina, Ekaterina; Poddubuskaya, Elena; Matrosova, Marina; Srimuninnimit, Vichien; Lindkær-Jensen, Steen

    2014-01-01

    The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer. Material and methods A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI), European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer–specific BR23) data were recorded at screening and after every 16 days of treatment. Computed tomography was performed at screening and every 32 days. Results The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in the placebo group. Only the increase in the placebo group was significant (P=0.013). The difference between the groups was significant in favor of BP-C1 (P=0.04). There was a significant difference (P=0.026) in favor of BP-C1 regarding Response Evaluation Criteria In Solid Tumors (RECIST) classification. The sum of lesions increased slightly in the patients receiving 64 days of continuous BP-C1 treatment, of whom 68.4% were classified as responders. The sum CTC-NCI toxicity score increased nonsignificantly in the BP-C1 group but significantly in the placebo group (P=0.05). The difference in increase between groups did not meet the level of significance (P=0.12). The sum toxicity score was reduced in the patients

  6. Source to sink element geochemistry and clay mineralogy in Lake Towuti, Indonesia: understanding climate-induced controls on sediment composition during the past 60 kyr BP

    NASA Astrophysics Data System (ADS)

    Morlock, Marina; Vogel, Hendrik; Nigg, Valentin; Hasberg, Ascelina; Melles, Martin; Russell, James M.; Bijaksana, Satria

    2016-04-01

    Al and high Mg concentrations and exerts a dominant control on the present-day sediment composition of Towuti's northern basin. This indicates that the Mahalona River and its tributaries cut deep into the laterite soils, transporting relatively unweathered material to the lake. In the past 60,000 years, the Al/Mg ratio is lowest between 35,000 and 15,000 years BP, and kaolinite is the dominant clay mineral during this period. During most of the Holocene and >35,000 years BP, Al/Mg is comparable to today and smectites (Holocene) and illites (MIS 3) are the most abundant clay minerals. The clay mineralogy suggests deeper soil erosion during wet interglacials and more surficial erosion during dry glacial climate conditions. These findings imply that erosion and element cycling are mainly driven by changes in precipitation amount and terrestrial runoff in Towuti's catchment. The Al/Mg ratio on the other hand points to a stronger (lesser) contribution of relatively unweathered sediments sourced from the Mahalona River catchment during dry (wet) phases, likely as a result of lake-level changes and associated changes in shoreline proximity to our coring sites.

  7. Once a year school-based deworming with praziquantel and albendazole combination may not be adequate for control of urogenital schistosomiasis and hookworm infection in Matuga District, Kwale County, Kenya

    PubMed Central

    2014-01-01

    prevalence and intensity of hookworm infection. Conclusions Once per year SBD programmes may not be adequate for controlling hookworm infection and urogenital schistosomiasis in rural areas of Kwale County. There is a need to consider expanded preventive chemotherapy strategies that will allow inclusion of the adult populations. Community-based health education campaigns focusing on increasing household latrine ownership and use, as a complementary measure to control STH and urogenital schistosomiasis in similar settings, may also be useful. PMID:24552246

  8. 78 FR 60270 - BP America Inc., BP Corporation North America Inc., BP America Production Company, and BP Energy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission BP America Inc., BP Corporation North America Inc., BP America Production Company, and BP Energy Company; Notice of Designation of Commission Staff as Non-Decisional With respect to an order issued by the Commission...

  9. Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5' cap.

    PubMed

    Modrak-Wojcik, Anna; Gorka, Michal; Niedzwiecka, Katarzyna; Zdanowski, Konrad; Zuberek, Joanna; Niedzwiecka, Anna; Stolarski, Ryszard

    2013-12-11

    Initiation is the rate-limiting step during mRNA 5' cap-dependent translation, and thus a target of a strict control in the eukaryotic cell. It is shown here by analytical ultracentrifugation and fluorescence spectroscopy that the affinity of the human translation inhibitor, eIF4E-binding protein (4E-BP1), to the translation initiation factor 4E is significantly higher when eIF4E is bound to the cap. The 4E-BP1 binding stabilizes the active eIF4E conformation and, on the other hand, can facilitate dissociation of eIF4E from the cap. These findings reveal the particular allosteric effects forming a thermodynamic cycle for the cooperative regulation of the translation initiation inhibition.

  10. Supervision of Student Teachers: How Adequate?

    ERIC Educational Resources Information Center

    Dean, Ken

    This study attempted to ascertain how adequately student teachers are supervised by college supervisors and supervising teachers. Questions to be answered were as follows: a) How do student teachers rate the adequacy of supervision given them by college supervisors and supervising teachers? and b) Are there significant differences between ratings…

  11. Small Rural Schools CAN Have Adequate Curriculums.

    ERIC Educational Resources Information Center

    Loustaunau, Martha

    The small rural school's foremost and largest problem is providing an adequate curriculum for students in a changing world. Often the small district cannot or is not willing to pay the per-pupil cost of curriculum specialists, specialized courses using expensive equipment no more than one period a day, and remodeled rooms to accommodate new…

  12. An Adequate Education Defined. Fastback 476.

    ERIC Educational Resources Information Center

    Thomas, M. Donald; Davis, E. E. (Gene)

    Court decisions historically have dealt with educational equity; now they are helping to establish "adequacy" as a standard in education. Legislatures, however, have been slow to enact remedies. One debate over education adequacy, though, is settled: Schools are not financed at an adequate level. This fastback is divided into three sections.…

  13. Funding the Formula Adequately in Oklahoma

    ERIC Educational Resources Information Center

    Hancock, Kenneth

    2015-01-01

    This report is a longevity, simulational study that looks at how the ratio of state support to local support effects the number of school districts that breaks the common school's funding formula which in turns effects the equity of distribution to the common schools. After nearly two decades of adequately supporting the funding formula, Oklahoma…

  14. Magmatic controls on eruption dynamics of the 1950 yr B.P. eruption of San Antonio Volcano, Tacaná Volcanic Complex, Mexico-Guatemala

    NASA Astrophysics Data System (ADS)

    Mora, Juan Carlos; Gardner, James Edward; Macías, José Luis; Meriggi, Lorenzo; Santo, Alba Patrizia

    2013-07-01

    San Antonio Volcano, in the Tacaná Volcanic Complex, erupted ~ 1950 yr. B.P., with a Pelean type eruption that produced andesitic pyroclastic surges and block-and-ash flows destroying part of the volcano summit and producing a horse-shoe shaped crater open to the SW. Between 1950 and 800 yr B.P. the eruption continued with effusive andesites followed by a dacite lava flow and a summit dome, all from a single magma batch. All products consist of phenocrysts and microphenocrysts of zoned plagioclase, amphibole, pyroxene, magnetite ± ilmenite, set in partially crystallized groundmass of glass and microlites of the same mineral phases, except for the lack of amphibole. Included in the andesitic blocks of the block-and-ash flow deposit are basaltic andesite enclaves with elongated and ellipsoidal forms and chilled margins. The enclaves have intersertal textures with brown glass between microphenocrysts of plagioclase, hornblende, pyroxene, and olivine, and minor proportions of phenocrysts of plagioclase, hornblende, and pyroxene. A compositional range obtained of blocks and enclaves resulted from mixing between andesite (866 °C ± 22) and basaltic andesite (enclaves, 932 °C ± 22), which may have triggered the explosive Pelean eruption. Vestiges of that mixing are preserved as complex compositional zones in plagioclase and clinopyroxene-rich reaction rims in amphibole in the andesite. Whole-rock chemistry, geothermometry, experimental petrology and modeling results suggest that after the mixing event the eruption tapped hybrid andesitic magma (≤ 900 °C) and ended with effusive dacitic magma (~ 825 °C), all of which were stored at ~ 200 MPa water pressure. A complex open-system evolution that involved crustal end-members best explains the generation of effusive dacite from the hybrid andesite. Amphibole in the dacite is rimmed by reaction products of plagioclase, orthopyroxene, and Fe-Ti oxides produced by decompression during ascent. Amphibole in the andesite

  15. Volume-associated ambulatory BP patterns in hemodialysis patients

    PubMed Central

    Agarwal, Rajiv

    2009-01-01

    Although volume excess causes hypertension whether it also affects circadian patterns of arterial pressures among hemodialysis patients remains unknown. To test the notion whether volume overload is associated with a unique BP “signature” a post-hoc analysis was performed among 145 patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) randomized controlled trial. Using 400 ambulatory BP recordings over 8 weeks comprising 35,302 measurements the trended cosinor model was found to be the best descriptor of BP chronobiology. The trended cosinor model may be described as a pattern of sinusoidal oscillation around a straight line with an upward trend during the interdialytic period and which has an intercept at the postdialysis time. Augmented volume removal therapy (AVRT) reduced the intercept systolic BP and increased the rate of rise in systolic BP over the interdialytic interval but had no effect on the systolic BP fluctuation (amplitude). Thus an elevated intercept and blunted slope pattern characterizes the “volume overload BP pattern” on ambulatory BP monitoring. Similar changes were seen for diastolic BP. AVRT neither restored dipping nor was associated with a lag-phenomenon for either the wake or sleep systolic BP. Lowering of systolic BP was greater than diastolic BP such that pulse pressure was reduced. An observational cohort of 37 patients followed for 6 months confirmed these findings. Randomized trials are now needed to evaluate the clinical impact of AVRT on hard outcomes since reduction of pulse pressure with this simple expedient has the potential to improve survival in hemodialysis patients. PMID:19528362

  16. Is a vegetarian diet adequate for children.

    PubMed

    Hackett, A; Nathan, I; Burgess, L

    1998-01-01

    The number of people who avoid eating meat is growing, especially among young people. Benefits to health from a vegetarian diet have been reported in adults but it is not clear to what extent these benefits are due to diet or to other aspects of lifestyles. In children concern has been expressed concerning the adequacy of vegetarian diets especially with regard to growth. The risks/benefits seem to be related to the degree of restriction of he diet; anaemia is probably both the main and the most serious risk but this also applies to omnivores. Vegan diets are more likely to be associated with malnutrition, especially if the diets are the result of authoritarian dogma. Overall, lacto-ovo-vegetarian children consume diets closer to recommendations than omnivores and their pre-pubertal growth is at least as good. The simplest strategy when becoming vegetarian may involve reliance on vegetarian convenience foods which are not necessarily superior in nutritional composition. The vegetarian sector of the food industry could do more to produce foods closer to recommendations. Vegetarian diets can be, but are not necessarily, adequate for children, providing vigilance is maintained, particularly to ensure variety. Identical comments apply to omnivorous diets. Three threats to the diet of children are too much reliance on convenience foods, lack of variety and lack of exercise.

  17. Maintaining adequate nutrition, not probiotic administration, prevents growth stunting and maintains skeletal muscle protein synthesis rates in a piglet model of colitis.

    PubMed

    Harding, Scott V; Adegoke, Olasunkanmi A J; Fraser, Keely G; Marliss, Errol B; Chevalier, Stéphanie; Kimball, Scot R; Jefferson, Leonard S; Wykes, Linda J

    2010-03-01

    Malnutrition and cytokine-induced catabolism are pervasive in children with inflammatory bowel diseases (IBD), however, the benefits of aggressive nutrition support or of probiotics on nutrient and functional deficiencies and growth remain unclear. Piglets with dextran sulfate (DS)-induced colitis consuming a 50% macronutrient restricted diet (C-MR) were compared with those receiving probiotics (C-MRP) or adequate nutrition (C-WN) and with healthy well-nourished controls (REF). C-WN versus REF had reduced growth (-34% chest circumference and -22% snout-to-rump length gain) and a tendency toward lesser weight gain, but no differences in skeletal muscle protein fractional synthesis rates (FSR) or initiation of translation via the mTOR pathway were observed. Compared with C-WN, the C-MR and C-MRP piglets had lower weight gain, growth, and skeletal muscle FSR, and lower phosphorylated p70S6K1 with higher eIF4E*4E-BP1, indicative of reduced initiation of protein translation. Finally, plasma leucine concentrations were positively correlated with weight and phosphorylated p70S6K1, whereas negatively correlated with eIF4E*4E-BP1. In conclusion, reductions in weight gain, growth, protein turnover, skeletal muscle FSR, and initiation of protein translation with moderate macronutrient restriction in colitis are not ameliorated by probiotic supplementation. However, maintaining adequate nutrient intake during colitis preserves whole body protein metabolism, but growth remains compromised.

  18. ED 03-2 HOME BLOOD PRESSURE MONITORING IS BETTER THAN OFFICE BP AND AMBULATORY BP: UPDATE.

    PubMed

    Kario, Kazuomi

    2016-09-01

    Out-of-office blood pressure (BP) measured by home BP monitoring (HBPM) or ambulatory BP monitoring (ABPM) was demonstrated to be superior to office BP for the prediction of cardiovascular events. The ABPM is superior to HBPM for detecting the all the BP-related risks throughout 24-hr, and the self-measured HBPM underestimates the risk of daytime stress hypertension and nocturnal hypertension. However, ABPM cannot always be provided in clinical practice, and home BP monitoring can be superior to ABPM as part of a home BP-guided antihypertension strategy in clinical practice. In clinical practice, we should use both ABPM and HBPM considering these device properties. We have developed the new ABPM device which is alternatively used as self-measure HBPM (Kario. Prog Cardiovasc Dis 2016, in press).The importance of on-treatment HBPM for the cardiovascular prognosis of hypertensive individuals was recently revealed in the largest real-world prospective study held to date, the Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study. That study of more than 21 000 hypertensive patients used HBPM, and the results demonstrated that when morning home systolic BP was well-controlled during the 2-year follow-up at < 125 mmHg, there was no increase in cardiovascular events even among the patients whose office systolic BP was ≥150 mmHg, compared with those with office systolic BP < 130 mmHg and morning home systolic BP < 125 mmHg. On the other hand, even when the office systolic BP of the HONEST study's hypertensive patients was well controlled at < 130 mmHg, the hazard ratio of cardiovascular events was 2.5 in the masked uncontrolled hypertension patients with morning systolic BP ≥145 mmHg compared with the well-controlled patients with morning systolic BP < 125 mmHg (Kario, et al. Hypertension 2014;64:989-996). The threshold of on-treatment morning BP for a significant increase in

  19. 29 CFR 505.5 - Adequate assurances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... amount of a weekly or monthly salary, talent or performance fee, hourly rate or other basis on which... requirements in paragraph (b) were approved by the Office of Management and Budget under control number...

  20. 29 CFR 505.5 - Adequate assurances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... amount of a weekly or monthly salary, talent or performance fee, hourly rate or other basis on which... requirements in paragraph (b) were approved by the Office of Management and Budget under control number...

  1. Adequate mathematical modelling of environmental processes

    NASA Astrophysics Data System (ADS)

    Chashechkin, Yu. D.

    2012-04-01

    In environmental observations and laboratory visualization both large scale flow components like currents, jets, vortices, waves and a fine structure are registered (different examples are given). The conventional mathematical modeling both analytical and numerical is directed mostly on description of energetically important flow components. The role of a fine structures is still remains obscured. A variety of existing models makes it difficult to choose the most adequate and to estimate mutual assessment of their degree of correspondence. The goal of the talk is to give scrutiny analysis of kinematics and dynamics of flows. A difference between the concept of "motion" as transformation of vector space into itself with a distance conservation and the concept of "flow" as displacement and rotation of deformable "fluid particles" is underlined. Basic physical quantities of the flow that are density, momentum, energy (entropy) and admixture concentration are selected as physical parameters defined by the fundamental set which includes differential D'Alembert, Navier-Stokes, Fourier's and/or Fick's equations and closing equation of state. All of them are observable and independent. Calculations of continuous Lie groups shown that only the fundamental set is characterized by the ten-parametric Galilelian groups reflecting based principles of mechanics. Presented analysis demonstrates that conventionally used approximations dramatically change the symmetries of the governing equations sets which leads to their incompatibility or even degeneration. The fundamental set is analyzed taking into account condition of compatibility. A high order of the set indicated on complex structure of complete solutions corresponding to physical structure of real flows. Analytical solutions of a number problems including flows induced by diffusion on topography, generation of the periodic internal waves a compact sources in week-dissipative media as well as numerical solutions of the same

  2. [Abdominal cure procedures. Adequate use of Nobecutan Spray].

    PubMed

    López Soto, Rosa María

    2009-12-01

    Open abdominal wounds, complicated by infection and/or risk of eventration tend to become chronic and usually require frequent prolonged cure. Habitual changing of bandages develop into one of the clearest risk factors leading to the deterioration of perilesional cutaneous integrity. This brings with it new complications which draw out the evolution of the process, provoking an important deterioration in quality of life for the person who suffers this and a considerable increase in health costs. What is needed is a product and a procedure which control the risk of irritation, which protect the skin, which favor a patient's comfort and which shorten treatment requirements while lowering health care expenses. This report invites medical personnel to think seriously about the scientific rationale, and treatment practice, as to why and how to apply Nobecutan adequately, this reports concludes stating the benefits in the adequate use of this product. The objective of this report is to guarantee the adequate use of this product in treatment of complicated abdominal wounds. This product responds to the needs which are present in these clinical cases favoring skin care apt isolation and protection, while at the same time, facilitating the placement and stability of dressings and bandages used to cure wounds. In order for this to happen, the correct use of this product is essential; medical personnel must pay attention to precautions and recommendations for proper application. The author's experiences in habitual handling of this product during various years, included in the procedures for standardized cures for these wounds, corroborates its usefulness; the author considers use of this product to be highly effective while being simple to apply; furthermore, one succeeds in providing quality care and optimizes resources employed.

  3. Why in 2016 are patients with hypertension not 100% controlled? A call to action.

    PubMed

    Redon, Josep; Mourad, Jean-Jacques; Schmieder, Roland E; Volpe, Massimo; Weiss, Thomas W

    2016-08-01

    The objective is to consider the problem of high blood pressure (BP), a leading global risk factor, associated with substantial morbidity and mortality. Despite the availability of treatment guidelines and a wide range of therapies, BP control is suboptimal in many countries. Recent data indicate that only around 40% of patients manage to achieve an adequate level of BP control. A group of international experts in the field of hypertension met in 2008 to consider this problem. The resulting white paper delivered an urgent call to action and identified six key issues for improving BP control. In 2015, a working group of investigators spontaneously undertook an action with the primary aim of considering the current hypertension management situation in Europe, to discuss whether the situation had changed since 2008 and to determine what can be learnt from the projects in other continents, such as the Canadian Hypertension Education Program, which has shown that higher levels of BP control can be achieved across a general population. The working group identified the main challenges affecting the improvement of BP control today and suggests five key actions: identify the BP treatment target of less than 140/90 mmHg for the majority of patients, simplify treatment strategies and encourage pill reduction, decrease therapeutic inertia, improve patient empowerment, and involve healthcare systems and reduce the prevailing focus on drug costs in many healthcare systems. Implementing key actions identified by the working group may help to improve achievement of better BP control across Europe. PMID:27270186

  4. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  5. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  6. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  7. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  8. 13 CFR 108.200 - Adequate capital for NMVC Companies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... VENTURE CAPITAL (âNMVCâ) PROGRAM Qualifications for the NMVC Program Capitalizing A Nmvc Company § 108.200 Adequate capital for NMVC Companies. You must meet the requirements of §§ 108.200-108.230 in order to... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for...

  9. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  10. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 1 2013-07-01 2013-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  11. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  12. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  13. 34 CFR 200.20 - Making adequate yearly progress.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Making adequate yearly progress. 200.20 Section 200.20... Basic Programs Operated by Local Educational Agencies Adequate Yearly Progress (ayp) § 200.20 Making... State data system; (vi) Include, as separate factors in determining whether schools are making AYP for...

  14. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  15. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  16. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  17. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  18. 40 CFR 716.25 - Adequate file search.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Adequate file search. 716.25 Section... ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of a person's responsibility to search records is limited to records in the location(s) where the...

  19. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  20. 9 CFR 305.3 - Sanitation and adequate facilities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Sanitation and adequate facilities. 305.3 Section 305.3 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... OF VIOLATION § 305.3 Sanitation and adequate facilities. Inspection shall not be inaugurated if...

  1. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 2 2011-07-01 2011-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  2. 40 CFR 51.354 - Adequate tools and resources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Adequate tools and resources. 51.354... Requirements § 51.354 Adequate tools and resources. (a) Administrative resources. The program shall maintain the administrative resources necessary to perform all of the program functions including...

  3. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  4. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  5. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  6. 10 CFR 1304.114 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Responsibility for maintaining adequate safeguards. 1304.114 Section 1304.114 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.114 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining...

  7. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES Qualifying for an SBIC License Capitalizing An Sbic § 107.200 Adequate capital...

  8. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  9. 21 CFR 201.5 - Drugs; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drugs; adequate directions for use. 201.5 Section 201.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use....

  10. 7 CFR 4290.200 - Adequate capital for RBICs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Adequate capital for RBICs. 4290.200 Section 4290.200 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND... Qualifications for the RBIC Program Capitalizing A Rbic § 4290.200 Adequate capital for RBICs. You must meet...

  11. "Something Adequate"? In Memoriam Seamus Heaney, Sister Quinlan, Nirbhaya

    ERIC Educational Resources Information Center

    Parker, Jan

    2014-01-01

    Seamus Heaney talked of poetry's responsibility to represent the "bloody miracle", the "terrible beauty" of atrocity; to create "something adequate". This article asks, what is adequate to the burning and eating of a nun and the murderous gang rape and evisceration of a medical student? It considers Njabulo…

  12. Phosphorylation and Rapid Relocalization of 53BP1 to Nuclear Foci upon DNA Damage

    PubMed Central

    Anderson, Lindsay; Henderson, Catherine; Adachi, Yasuhisa

    2001-01-01

    53BP1 is a human BRCT protein that was originally identified as a p53-interacting protein by the Saccharomyces cerevisiae two-hybrid screen. Although the carboxyl-terminal BRCT domain shows similarity to Crb2, a DNA damage checkpoint protein in fission yeast, there is no evidence so far that implicates 53BP1 in the checkpoint. We have identified a Xenopus homologue of 53BP1 (XL53BP1). XL53BP1 is associated with chromatin and, in some cells, localized to a few large foci under normal conditions. Gamma-ray irradiation induces increased numbers of the nuclear foci in a dose-dependent manner. The damage-induced 53BP1 foci appear rapidly (in 30 min) after irradiation, and de novo protein synthesis is not required for this response. In human cells, 53BP1 foci colocalize with Mrel1 foci at later stages of the postirradiation period. XL53BP1 is hyperphosphorylated after X-ray irradiation, and inhibitors of ATM-related kinases delay the relocalization and reduce the phosphorylation of XL53BP1 in response to X-irradiation. In AT cells, which lack ATM kinase, the irradiation-induced responses of 53BP1 are similarly affected. These results suggest a role for 53BP1 in the DNA damage response and/or checkpoint control which may involve signaling of damage to p53. PMID:11238909

  13. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment.

  14. Improving access to adequate pain management in Taiwan.

    PubMed

    Scholten, Willem

    2015-06-01

    There is a global crisis in access to pain management in the world. WHO estimates that 4.65 billion people live in countries where medical opioid consumption is near to zero. For 2010, WHO considered a per capita consumption of 216.7 mg morphine equivalents adequate, while Taiwan had a per capita consumption of 0.05 mg morphine equivalents in 2007. In Asia, the use of opioids is sensitive because of the Opium Wars in the 19th century and for this reason, the focus of controlled substances policies has been on the prevention of diversion and dependence. However, an optimal public health outcome requires that also the beneficial aspects of these substances are acknowledged. Therefore, WHO recommends a policy based on the Principle of Balance: ensuring access for medical and scientific purposes while preventing diversion, harmful use and dependence. Furthermore, international law requires that countries ensure access to opioid analgesics for medical and scientific purposes. There is evidence that opioid analgesics for chronic pain are not associated with a major risk for developing dependence. Barriers for access can be classified in the categories of overly restrictive laws and regulations; insufficient medical training on pain management and problems related to assessment of medical needs; attitudes like an excessive fear for dependence or diversion; and economic and logistical problems. The GOPI project found many examples of such barriers in Asia. Access to opioid medicines in Taiwan can be improved by analysing the national situation and drafting a plan. The WHO policy guidelines Ensuring Balance in National Policies on Controlled Substances can be helpful for achieving this purpose, as well as international guidelines for pain treatment. PMID:26068436

  15. CacyBP/SIP nuclear translocation induced by gastrin promotes gastric cancer cell proliferation

    PubMed Central

    Zhai, Hui-Hong; Meng, Juan; Wang, Jing-Bo; Liu, Zhen-Xiong; Li, Yuan-Fei; Feng, Shan-Shan

    2014-01-01

    AIM: To investigate the role of nuclear translocation of calcyclin binding protein, also called Siah-1 interacting protein (CacyBP/SIP), in gastric carcinogenesis. METHODS: The expression of CacyBP/SIP protein in gastric cancer cell lines was detected by Western blot. Immunofluorescence experiments were performed on gastric cancer cell lines that had been either unstimulated or stimulated with gastrin. To confirm the immunofluorescence findings, the relative abundance of CacyBP/SIP in nuclear and cytoplasmic compartments was assessed by Western blot. The effect of nuclear translocation of CacyBP/SIP on cell proliferation was examined using MTT assay. The colony formation assay was used to measure clonogenic cell survival. The effect of CacyBP/SIP nuclear translocation on cell cycle progression was investigated. Two CacyBP/SIP-specific siRNA vectors were designed and constructed to inhibit CacyBP/SIP expression in order to reduce the nuclear translocation of CacyBP/SIP, and the expression of CacyBP/SIP in stably transfected cells was determined by Western blot. The effect of inhibiting CacyBP/SIP nuclear translocation on cell proliferation was then assessed. RESULTS: CacyBP/SIP protein was present in most of gastric cancer cell lines. In unstimulated cells, CacyBP/SIP was distributed throughout the cytoplasm; while in stimulated cells, CacyBP/SIP was found mainly in the perinuclear region. CacyBP/SIP nuclear translocation generated a growth-stimulatory effect on cells. The number of colonies in the CacyBP/SIP nuclear translocation group was significantly higher than that in the control group. The percentage of stimulated cells in G1 phase was significantly lower than that of control cells (69.70% ± 0.46% and 65.80% ± 0.60%, control cells and gastrin-treated SGC7901 cells, P = 0.008; 72.99% ± 0.46% and 69.36% ± 0.51%, control cells and gastrin-treated MKN45 cells, P = 0.022). CacyBP/SIPsi1 effectively down-regulated the expression of CacyBP/SIP, and cells stably

  16. The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction

    PubMed Central

    Miller, William P.; Mihailescu, Maria L.; Yang, Chen; Barber, Alistair J.; Kimball, Scot R.; Jefferson, Leonard S.; Dennis, Michael D.

    2016-01-01

    Purpose The translational repressor 4E-BP1 interacts with the mRNA cap-binding protein eIF4E and thereby promotes cap-independent translation of mRNAs encoding proteins that contribute to diabetic retinopathy. Interaction of 4E-BP1 with eIF4E is enhanced in the retina of diabetic rodents, at least in part, as a result of elevated 4E-BP1 protein expression. In the present study, we examined the role of 4E-BP1 in diabetes-induced visual dysfunction, as well as the mechanism whereby hyperglycemia promotes 4E-BP1 expression. Methods Nondiabetic and diabetic wild-type and 4E-BP1/2 knockout mice were evaluated for visual function using a virtual optomotor test (Optomotry). Retinas were harvested from nondiabetic and type 1 diabetic mice and analyzed for protein abundance and posttranslational modifications. Similar analyses were performed on cells in culture exposed to hyperglycemic conditions or an O-GlcNAcase inhibitor (Thiamet G [TMG]). Results Diabetes-induced visual dysfunction was delayed in mice deficient of 4E-BP1/2 as compared to controls. 4E-BP1 protein expression was enhanced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in retinal cells in culture. A similar elevation in 4E-BP1 expression was observed with TMG. The rate of 4E-BP1 degradation was significantly prolonged by either hyperglycemic conditions or TMG. A PEST motif in the C-terminus of 4E-BP1 regulated polyubiquitination, turnover, and binding of an E3 ubiquitin ligase complex containing CUL3. Conclusions The findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif. PMID:26998719

  17. Electronic states of BP, BP +, BP -, B 2P 2, B2P2- and B2P2+

    NASA Astrophysics Data System (ADS)

    Linguerri, Roberto; Komiha, Najia; Oswald, Rainer; Mitrushchenkov, Alexander; Rosmus, Pavel

    2008-05-01

    Using augmented sextuple zeta basis sets and internally contracted multireference configuration interaction (MRCI) wavefunctions, potential energy, electric dipole and transition moments have been computed for the X 3Π, a 1Σ +, b 1Π and A 3Σ - states of BP, X 2Σ + and A 2Π states of BP - and X 4Σ - and A 4Π states of BP +. From these data spectroscopic constants, radiative transition probabilities and photoelectron spectra of BP - and BP have been evaluated. The non-vanishing spin-orbit coupling elements between the four low lying triplet and singlet states of the neutral BP have also been calculated from MRCI wavefunctions. The treatment of the corresponding perturbations in the manifold of dense rovibrational states in the three lowest states would require a precise knowledge of the electronic excitation energies. Our best singlet-triplet separations (X-a) are calculated to be 2412 cm -1 (MRCI) and 2482 cm -1 (restricted coupled cluster with perturbative triples (RCCSD(T))) with an estimated error bound of about ±200 cm -1. All three states have long radiative lifetimes with cascading among the rovibrational levels of different states. The ionization energy IE e of BP is calculated to be 9.22 eV (MRCI) and 9.48 eV (RCCSD(T)), the electron affinity EA e 2.51 eV (MRCI) and 2.74 eV (RCCSD(T)). The photoelectron spectra of BP and BP - have been obtained from the Franck-Condon factors of the MRCI potentials. For the UV spectroscopy the dipole allowed radiative transition probabilities are given for A 3Σ - ↔ X 3Π, b 1Π ↔ a 1Σ + of BP, A 2Π ↔ X 2Σ + of BP - and A 4Π ↔ X 4Σ - of BP +. The ionization energy IE e of B 2P 2 of 8.71 eV and the electron affinity EA e of 2.34 eV have been calculated by the RCCSD(T)/aVQZ approach. Also the harmonic vibrational wavenumbers for the electronic ground states of the ions B2P2+ and B2P2- are given.

  18. Eastern Andean environmental and climate synthesis for the last 2000 years BP from terrestrial pollen and charcoal records of Patagonia

    NASA Astrophysics Data System (ADS)

    Sottile, G. D.; Echeverria, M. E.; Mancini, M. V.; Bianchi, M. M.; Marcos, M. A.; Bamonte, F. P.

    2015-06-01

    The Southern Hemisphere Westerly Winds (SWW) constitute an important zonal circulation system that dominates the dynamics of Southern Hemisphere mid-latitude climate. Little is known about climatic changes in the Southern South America in comparison to the Northern Hemisphere due to the low density of proxy records, and adequate chronology and sampling resolution to address environmental changes of the last 2000 years. Since 2009, new pollen and charcoal records from bog and lakes in northern and southern Patagonia at the east side of the Andes have been published with an adequate calibration of pollen assemblages related to modern vegetation and ecological behaviour. In this work we improve the chronological control of some eastern Andean previously published sequences and integrate pollen and charcoal dataset available east of the Andes to interpret possible environmental and SWW variability at centennial time scales. Through the analysis of modern and past hydric balance dynamics we compare these scenarios with other western Andean SWW sensitive proxy records for the last 2000 years. Due to the distinct precipitation regimes that exist between Northern (40-45° S) and Southern Patagonia (48-52° S) pollen sites locations, shifts on latitudinal and strength of the SWW results in large changes on hydric availability on forest and steppe communities. Therefore, we can interpret fossil pollen dataset as changes on paleohydric balance at every single site by the construction of paleohydric indices and comparison to charcoal records during the last 2000 cal yrs BP. Our composite pollen-based Northern and Southern Patagonia indices can be interpreted as changes in latitudinal variation and intensity of the SWW respectively. Dataset integration suggest poleward SWW between 2000 and 750 cal yrs BP and northward-weaker SWW during the Little Ice Age (750-200 cal yrs BP). These SWW variations are synchronous to Patagonian fire activity major shifts. We found an in phase

  19. Understanding Your Adequate Yearly Progress (AYP), 2011-2012

    ERIC Educational Resources Information Center

    Missouri Department of Elementary and Secondary Education, 2011

    2011-01-01

    The "No Child Left Behind Act (NCLB) of 2001" requires all schools, districts/local education agencies (LEAs) and states to show that students are making Adequate Yearly Progress (AYP). NCLB requires states to establish targets in the following ways: (1) Annual Proficiency Target; (2) Attendance/Graduation Rates; and (3) Participation Rates.…

  20. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  1. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  2. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  3. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  4. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Adequate exploration plan. 970.404...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of...

  5. Adequate Schools and Inadequate Education: An Anthropological Perspective.

    ERIC Educational Resources Information Center

    Wolcott, Harry F.

    To illustrate his claim that schools generally do a remarkably good job of schooling while the society makes inadequate use of other means to educate young people, the author presents a case history of a young American (identified pseudonymously as "Brad") whose schooling was adequate but whose education was not. Brad, jobless and homeless,…

  6. Comparability and Reliability Considerations of Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Maier, Kimberly S.; Maiti, Tapabrata; Dass, Sarat C.; Lim, Chae Young

    2012-01-01

    The purpose of this study is to develop an estimate of Adequate Yearly Progress (AYP) that will allow for reliable and valid comparisons among student subgroups, schools, and districts. A shrinkage-type estimator of AYP using the Bayesian framework is described. Using simulated data, the performance of the Bayes estimator will be compared to…

  7. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Adequate capital for Licensees. 107.200 Section 107.200 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS... operate actively in accordance with your Articles and within the context of your business plan,...

  8. Assessing Juvenile Sex Offenders to Determine Adequate Levels of Supervision.

    ERIC Educational Resources Information Center

    Gerdes, Karen E.; And Others

    1995-01-01

    This study analyzed the internal consistency of four inventories used by Utah probation officers to determine adequate and efficacious supervision levels and placement for juvenile sex offenders. Three factors accounted for 41.2 percent of variance (custodian's and juvenile's attitude toward intervention, offense characteristics, and historical…

  9. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... identifiable personal data and automated systems shall be adequately trained in the security and privacy of... records in which identifiable personal data are processed or maintained, including all reports and output... personal records or data; must minimize, to the extent practicable, the risk that skilled technicians...

  10. Do Beginning Teachers Receive Adequate Support from Their Headteachers?

    ERIC Educational Resources Information Center

    Menon, Maria Eliophotou

    2012-01-01

    The article examines the problems faced by beginning teachers in Cyprus and the extent to which headteachers are considered to provide adequate guidance and support to them. Data were collected through interviews with 25 school teachers in Cyprus, who had recently entered teaching (within 1-5 years) in public primary schools. According to the…

  11. Both G3BP1 and G3BP2 contribute to stress granule formation.

    PubMed

    Matsuki, Hideaki; Takahashi, Masahiko; Higuchi, Masaya; Makokha, Grace N; Oie, Masayasu; Fujii, Masahiro

    2013-02-01

    Upon exposure to various environmental stresses such as arsenite, hypoxia, and heat shock, cells inhibit their translation and apoptosis and then repair stress-induced alterations, such as DNA damage and the accumulation of misfolded proteins. These types of stresses induce the formation of cytoplasmic RNA granules called stress granules (SGs). SGs are storage sites for the many mRNAs released from disassembled polysomes under these stress conditions and are essential for the selective translation of stress-inducible genes. Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo-multimer and a hetero-multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.

  12. The relationship between prenatal exposure to BP-3 and Hirschsprung's disease.

    PubMed

    Huo, Weiwei; Cai, Peng; Chen, Minjian; Li, Hongxing; Tang, Junwei; Xu, Chao; Zhu, Dongmei; Tang, Weibing; Xia, Yankai

    2016-02-01

    Hirschsprung's disease (HSCR) is neonatal intestinal abnormality which derived from the faliure of enteric neural crest cells migration to hindgut during embryogenesis from 5 to 12 weeks. Currenly, the knowledge of environmental factors contributing to HSCR is still scarce. Benzophenone-3 (BP-3) is one of the most widely used UV filters, and has weak estrogen and strong anti-androgenic effects. In order to examine the effect of maternal BP-3 exposure on development of offspring and explore the potential mechanism, we conducted case and control study and in vitro study. In this work, BP-3 concertrations in maternal urine was detected by ultra-high performance liquid chromatography. Besides, we investigated the cytotoxicity and receptor tyrosine kinase (RET) expression in cells exposed to BP-3. The results showed that maternal BP-3 exposure was associated with offspring's HSCR in the population as well as inhibited migration of 293T and SH-SY5Y cells. What's more, we discovered dose-response relationship between RET expression and BP-3 exposure dose, and miR-218 and some other genes involved in SLIT2/ROBO1-miR-218-RET/PLAG1 pathway were also related to BP-3 exposure. Therefore, we deduced that BP-3 influenced cell migration via SLIT2/ROBO1-miR-218-RET/PLAG1 pathway. Our study firstly revealed the relationship between maternal BP-3 exposure and HSCR as well as its potential mechanism.

  13. Spectroscopic observations of ASASSN-15bp

    NASA Astrophysics Data System (ADS)

    Williams, S. C.; Darnley, M. J.; Bode, M. F.; Copperwheat, C. M.

    2015-01-01

    We report spectroscopic observations of the optical transient ASASSN-15bp (ATel #6981) taken on 2015 January 25.31 UT using the FRODOSpec spectrograph (Barnsley et al. 2012) on the Liverpool Telescope (Steele et al. 2004).

  14. BP: synthesis and properties of boron phosphide

    NASA Astrophysics Data System (ADS)

    Woo, Katherine; Lee, Kathleen; Kovnir, Kirill

    2016-07-01

    Cubic boron phosphide, BP, is notorious for its difficult synthesis, thus preventing it from being a widely used material in spite of having numerous favorable technological properties. In the current work, three different methods of synthesis are developed and compared: from the high temperature reaction of elements, Sn flux assisted synthesis, and a solid state metathesis reaction. Structural and optical properties of the products synthesized from the three methods were thoroughly characterized. Solid state metathesis is shown to be the cleanest and most efficient method in terms of reaction temperature and time. Synthesis by Sn flux resulted in a novel Sn-doped BP compound. Undoped BP samples exhibit an optical bandgap of ∼2.2 eV while Sn-doped BP exhibits a significantly smaller bandgap of 1.74 eV. All synthesized samples show high stability in concentrated hydrochloric acid, saturated sodium hydroxide solutions, and fresh aqua regia.

  15. No detectable association of IGF2BP2 and SLC30A8 genes with type 2 diabetes in the population of Hyderabad, India☆

    PubMed Central

    Kommoju, Uma Jyothi; Maruda, Jayaraj; Kadarkarai, Subburaj; Irgam, Kumuda; Kotla, Jaya Prasad; Velaga, Lakshmi; Mohan Reddy, Battini

    2013-01-01

    Genome-wide association studies identified novel genes associated with T2DM which have been replicated in different populations. We try to examine here if certain frequently replicated SNPs of Insulin growth factor 2 m-RNA binding protein 2 (IGF2BP2) (rs4402960, rs1470579) and Solute Carrier family 30 member 8 (SLC30A8) (rs13266634) genes, known to be implicated in insulin pathway, are associated with T2DM in the population of Hyderabad, which is considered to be a diabetic capital of India. Genotyping of the 1379 samples, 758 cases and 621 controls, for the SNPs was performed on sequenom massarray platform. The logistic regression analysis was done using SPSS software and the post-hoc power of the study was estimated using G power. The allele and genotype frequencies were similar between cases and controls, both for SNPs of IGF2BP2 and SLC30A8 genes. Logistic regression did not reveal significant allelic or genotypic association of any of the three SNPs with T2DM. Despite large sample size and adequate power, we could not replicate the association of IGF2BP2 and SLC30A8 SNPs with T2DM in our sample from Hyderabad (A.P.), India, albeit another study based on much larger sample but from heterogeneous populations from the northern parts of India showed significant association of two of the above 3 SNPs, suggesting variable nature of susceptibility of these genes in different ethnic groups. Although the IGF2BP2 and SLC30A8 genes are important in the functional pathway of Insulin secretion, it appears that these genes do not play a significant role in the susceptibility to T2DM in this population. PMID:25606370

  16. Adequate iron stores and the 'Nil nocere' principle.

    PubMed

    Hollán, S; Johansen, K S

    1993-01-01

    There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial pathogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron

  17. Calcium modulates promoter occupancy by the Entamoeba histolytica Ca2+-binding transcription factor URE3-BP.

    PubMed

    Gilchrist, Carol A; Leo, Megan; Line, C Genghis; Mann, Barbara J; Petri, William A

    2003-02-14

    The Entamoeba histolytica upstream regulatory element 3-binding protein (URE3-BP) binds to the URE3 sequence of the Gal/GalNAc-inhibitable lectin hgl5 and ferredoxin 1 (fdx) gene promoters. This binding can be inhibited in vitro by addition of calcium. Two EF-hand motifs, which are associated with the ability to bind calcium, are present in the amino acid sequence of URE3-BP. Mutation of the second EF-hand motif in URE3-BP resulted in the loss of calcium inhibition of DNA binding as monitored by electrophoretic mobility shift assay. Chromatin immunoprecipitation assays revealed that URE3-BP was physically bound to the hgl5 and fdx promoters in vivo. Parasite intracellular calcium concentrations were altered by changes in extracellular calcium. Promoter occupancy was lost when intracellular calcium levels were increased by coordinate increases in extracellular calcium. Increased intracellular calcium also resulted in decreased levels of URE3-BP mRNA. Together these results demonstrate that changes in extracellular calcium result in changes in URE3-BP mRNA and in the ability of URE3-BP to bind to URE3-containing promoters. Modulation of URE3-BP by calcium may represent an important mechanism of control of gene expression in E. histolytica.

  18. Differential Spatial Expression and Subcellular Localization of CtBP Family Members in Rodent Brain

    PubMed Central

    Richter, Karin; Lazarevic, Vesna; Altrock, Wilko D.; Fischer, Klaus-Dieter; Gundelfinger, Eckart D.; Fejtova, Anna

    2012-01-01

    C-terminal binding proteins (CtBPs) are well-characterized nuclear transcriptional co-regulators. In addition, cytoplasmic functions were discovered for these ubiquitously expressed proteins. These include the involvement of the isoform CtBP1-S/BARS50 in cellular membrane-trafficking processes and a role of the isoform RIBEYE as molecular scaffolds in ribbons, the presynaptic specializations of sensory synapses. CtBPs were suggested to regulate neuronal differentiation and they were implied in the control of gene expression during epileptogenesis. However, the expression patterns of CtBP family members in specific brain areas and their subcellular localizations in neurons in situ are largely unknown. Here, we performed comprehensive assessment of the expression of CtBP1 and CtBP2 in mouse brain at the microscopic and the ultra-structural levels using specific antibodies. We quantified and compared expression levels of both CtBPs in biochemically isolated brain fractions containing cellular nuclei or synaptic compartment. Our study demonstrates differential regional and subcellular expression patterns for the two CtBP family members in brain and reveals a previously unknown synaptic localization for CtBP2 in particular brain regions. Finally, we propose a mechanism of differential synapto-nuclear targeting of its splice variants CtBP2-S and CtBP2-L in neurons. PMID:22745816

  19. Differential spatial expression and subcellular localization of CtBP family members in rodent brain.

    PubMed

    Hübler, Diana; Rankovic, Marija; Richter, Karin; Lazarevic, Vesna; Altrock, Wilko D; Fischer, Klaus-Dieter; Gundelfinger, Eckart D; Fejtova, Anna

    2012-01-01

    C-terminal binding proteins (CtBPs) are well-characterized nuclear transcriptional co-regulators. In addition, cytoplasmic functions were discovered for these ubiquitously expressed proteins. These include the involvement of the isoform CtBP1-S/BARS50 in cellular membrane-trafficking processes and a role of the isoform RIBEYE as molecular scaffolds in ribbons, the presynaptic specializations of sensory synapses. CtBPs were suggested to regulate neuronal differentiation and they were implied in the control of gene expression during epileptogenesis. However, the expression patterns of CtBP family members in specific brain areas and their subcellular localizations in neurons in situ are largely unknown. Here, we performed comprehensive assessment of the expression of CtBP1 and CtBP2 in mouse brain at the microscopic and the ultra-structural levels using specific antibodies. We quantified and compared expression levels of both CtBPs in biochemically isolated brain fractions containing cellular nuclei or synaptic compartment. Our study demonstrates differential regional and subcellular expression patterns for the two CtBP family members in brain and reveals a previously unknown synaptic localization for CtBP2 in particular brain regions. Finally, we propose a mechanism of differential synapto-nuclear targeting of its splice variants CtBP2-S and CtBP2-L in neurons.

  20. Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice.

    PubMed

    Kon, Ning; Zhong, Jiayun; Qiang, Li; Accili, Domenico; Gu, Wei

    2012-02-10

    It is well accepted that the Mdm2 ubiquitin ligase acts as a major factor in controlling p53 stability and activity in vivo. Although several E3 ligases have been reported to be involved in Mdm2-independent p53 degradation, the roles of these ligases in p53 regulation in vivo remain largely unknown. To elucidate the physiological role of the ubiquitin ligase ARF-BP1, we generated arf-bp1 mutant mice. We found that inactivation of arf-bp1 during embryonic development in mice resulted in p53 activation and embryonic lethality, but the mice with arf-bp1 deletion specifically in the pancreatic β-cells (arf-bp1(FL/Y)/RIP-cre) were viable and displayed no obvious abnormality after birth. Interestingly, these mice showed dramatic loss of β-cells as mice aged, and >50% of these mice died of severe diabetic symptoms before reaching 1 year of age. Notably, the diabetic phenotype of these mice was largely reversed by concomitant deletion of p53, and the life span of the mice was significantly extended (p53(LFL/FL)/arf-bp1(FL/Y)/RIP-cre). These findings underscore an important role of ARF-BP1 in maintaining β-cell homeostasis in aging mice and reveal that the stability of p53 is critically regulated by ARF-BP1 in vivo.

  1. Preparation of PLLA/bpV(pic) microspheres and their effect on nerve cells.

    PubMed

    Lin, Qiang; Chen, Hai-yun; Li, Hao-shen; Cai, Yang-ting

    2014-02-01

    In this study, we prepared PLLA/bpV(pic) microspheres, a bpV(pic) controlled release system and examined their ability to protect nerve cells and promote axonal growth. PLLA microspheres were prepared by employing the o/w single emulsification-evaporation technique. Neural stem cells and dorsal root ganglia were divided into 3 groups in terms of the treatment they received: a routine medium group (cultured in DMEM), a PLLA microsphere group (DMEM containing PLLA microspheres alone) and a PLLA/bpV(pic) group [DMEM containing PLLA/bpV(pic) microspheres]. The effects of PLLA/bpV(pic) microspheres were evaluated by the live-dead test and measurement of axonal length. Our results showed that PLLA/bpV(pic) granulation rate was (88.2±5.6)%; particle size was (16.8±3.1)%, drug loading was (4.05±0.3)%; encapsulation efficiency was (48.5±1.8)%. The release time lasted for 30 days. In PLLA/bpV(pic) microsphere group, the cell survival rate was (95.2 ±4.77)%, and the length of dorsal root ganglion (DRG) was 718±95 μm, which were all significantly greater than those in ordinary routine medium group and PLLA microsphere group. This preliminary test results showed the PLLA/bpV(pic) microspheres were successfully prepared and they could promote the survival and growth of neural cells in DRG.

  2. G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits.

    PubMed

    Kedersha, Nancy; Panas, Marc D; Achorn, Christopher A; Lyons, Shawn; Tisdale, Sarah; Hickman, Tyler; Thomas, Marshall; Lieberman, Judy; McInerney, Gerald M; Ivanov, Pavel; Anderson, Paul

    2016-03-28

    Mammalian stress granules (SGs) contain stalled translation preinitiation complexes that are assembled into discrete granules by specific RNA-binding proteins such as G3BP. We now show that cells lacking both G3BP1 and G3BP2 cannot form SGs in response to eukaryotic initiation factor 2α phosphorylation or eIF4A inhibition, but are still SG-competent when challenged with severe heat or osmotic stress. Rescue experiments using G3BP1 mutants show that phosphomimetic G3BP1-S149E fails to rescue SG formation, whereas G3BP1-F33W, a mutant unable to bind G3BP partner proteins Caprin1 or USP10, rescues SG formation. Caprin1/USP10 binding to G3BP is mutually exclusive: Caprin binding promotes, but USP10 binding inhibits, SG formation. G3BP interacts with 40S ribosomal subunits through its RGG motif, which is also required for G3BP-mediated SG formation. We propose that G3BP mediates the condensation of SGs by shifting between two different states that are controlled by the phosphorylation of S149 and by binding to Caprin1 or USP10. PMID:27022092

  3. G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits.

    PubMed

    Kedersha, Nancy; Panas, Marc D; Achorn, Christopher A; Lyons, Shawn; Tisdale, Sarah; Hickman, Tyler; Thomas, Marshall; Lieberman, Judy; McInerney, Gerald M; Ivanov, Pavel; Anderson, Paul

    2016-03-28

    Mammalian stress granules (SGs) contain stalled translation preinitiation complexes that are assembled into discrete granules by specific RNA-binding proteins such as G3BP. We now show that cells lacking both G3BP1 and G3BP2 cannot form SGs in response to eukaryotic initiation factor 2α phosphorylation or eIF4A inhibition, but are still SG-competent when challenged with severe heat or osmotic stress. Rescue experiments using G3BP1 mutants show that phosphomimetic G3BP1-S149E fails to rescue SG formation, whereas G3BP1-F33W, a mutant unable to bind G3BP partner proteins Caprin1 or USP10, rescues SG formation. Caprin1/USP10 binding to G3BP is mutually exclusive: Caprin binding promotes, but USP10 binding inhibits, SG formation. G3BP interacts with 40S ribosomal subunits through its RGG motif, which is also required for G3BP-mediated SG formation. We propose that G3BP mediates the condensation of SGs by shifting between two different states that are controlled by the phosphorylation of S149 and by binding to Caprin1 or USP10.

  4. Quantifying dose to the reconstructed breast: Can we adequately treat?

    SciTech Connect

    Chung, Eugene; Marsh, Robin B.; Griffith, Kent A.; Moran, Jean M.; Pierce, Lori J.

    2013-04-01

    To evaluate how immediate reconstruction (IR) impacts postmastectomy radiotherapy (PMRT) dose distributions to the reconstructed breast (RB), internal mammary nodes (IMN), heart, and lungs using quantifiable dosimetric end points. 3D conformal plans were developed for 20 IR patients, 10 autologous reconstruction (AR), and 10 expander-implant (EI) reconstruction. For each reconstruction type, 5 right- and 5 left-sided reconstructions were selected. Two plans were created for each patient, 1 with RB coverage alone and 1 with RB + IMN coverage. Left-sided EI plans without IMN coverage had higher heart Dmean than left-sided AR plans (2.97 and 0.84 Gy, p = 0.03). Otherwise, results did not vary by reconstruction type and all remaining metrics were evaluated using a combined AR and EI dataset. RB coverage was adequate regardless of laterality or IMN coverage (Dmean 50.61 Gy, D95 45.76 Gy). When included, IMN Dmean and D95 were 49.57 and 40.96 Gy, respectively. Mean heart doses increased with left-sided treatment plans and IMN inclusion. Right-sided treatment plans and IMN inclusion increased mean lung V{sub 20}. Using standard field arrangements and 3D planning, we observed excellent coverage of the RB and IMN, regardless of laterality or reconstruction type. Our results demonstrate that adequate doses can be delivered to the RB with or without IMN coverage.

  5. Choices for achieving adequate dietary calcium with a vegetarian diet.

    PubMed

    Weaver, C M; Proulx, W R; Heaney, R

    1999-09-01

    To achieve adequate dietary calcium intake, several choices are available that accommodate a variety of lifestyles and tastes. Liberal consumption of dairy products in the diet is the approach of most Americans. Some plants provide absorbable calcium, but the quantity of vegetables required to reach sufficient calcium intake make an exclusively plant-based diet impractical for most individuals unless fortified foods or supplements are included. Also, dietary constituents that decrease calcium retention, such as salt, protein, and caffeine, can be high in the vegetarian diet. Although it is possible to obtain calcium balance from a plant-based diet in a Western lifestyle, it may be more convenient to achieve calcium balance by increasing calcium consumption than by limiting other dietary factors.

  6. Genetic Modification of Preimplantation Embryos: Toward Adequate Human Research Policies

    PubMed Central

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects. PMID:15016248

  7. MST's Programmable Power Supplies: Bt Update, Bp Prototype

    NASA Astrophysics Data System (ADS)

    Holly, D. J.; Chapman, B. E.; McCollam, K. J.; Morin, J. C.; Thomas, M. A.

    2013-10-01

    MST's toroidal field programmable power supply (Bt PPS) has now been in operation for several years and has provided important new capabilities. One of the primary goals for the Bt PPS is the partial optimization of inductive current profile control, involving control of the poloidal electric field. The Bt PPS has achieved fluctuation reduction over MST's entire range of Ip. At the largest Ip, the Bt PPS achieves fluctuation reduction with a smaller poloidal electric field than the previous passive system, implying that substantially longer periods of current profile control may be possible. The Bt PPS has also been used to produce Ohmic tokamak plasmas in MST. With an applied toroidal field of 0.135 T, and q(a) > 2, the estimated energy confinement time is roughly consistent with neo-Alcator scaling. Driving q(a) < 2 with larger Ip, the confinement time degrades, but the discharge duration does not terminate prematurely. To fully optimize current profile control and to test MST operational limits, a PPS is also needed for the Bp circuit. Currently in prototype stage, the Bp PPS will feature a number of innovations to increase its flexibility and performance. Isolated charging, control, and monitor systems will eliminate charging relays, reduce coupling between modules, and minimize capacitor heating. Seven-level pulse width modulation will reduce output ripple and switching losses. Solid state shorting bars will eliminate shorting relays and minimize wiring. A balanced switching algorithm will minimize capacitive noise generation. Work supported by U. S. D. o. E.

  8. Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells

    PubMed Central

    2013-01-01

    Background Regulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis. G3BPs constitute a family of mRNA-binding proteins, shown to be overexpressed in several cancer types, including breast, colon and pancreas cancer. G3BP has been reported to both stabilize and induce degradation of specific mRNAs. Results Here, we show that G3BP1, but not G3BP2, supports proliferation of several breast cancer cell lines. Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2–3 fold increased expression. Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion. Conclusions This indicates a novel role for G3BP1 in the regulation of cell proliferation in breast cancer cells, perhaps via a regulatory effect on PMP22 expression. PMID:24321297

  9. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine.

    PubMed

    Huber, Samuel; Gagliani, Nicola; Zenewicz, Lauren A; Huber, Francis J; Bosurgi, Lidia; Hu, Bo; Hedl, Matija; Zhang, Wei; O'Connor, William; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Booth, Carmen J; Cho, Judy H; Ouyang, Wenjun; Abraham, Clara; Flavell, Richard A

    2012-11-01

    Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer. This association could be explained by the hypothesis that the same factors and pathways important for wound healing also promote tumorigenesis. A sensor of tissue damage should induce these factors to promote tissue repair and regulate their action to prevent development of cancer. Interleukin 22 (IL-22), a cytokine of the IL-10 superfamily, has an important role in colonic epithelial cell repair, and its levels are increased in the blood and intestine of inflammatory bowel disease patients. This cytokine can be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP, also known as IL22RA2); however, the significance of endogenous IL-22BP in vivo and the pathways that regulate this receptor are unknown. Here we describe that IL-22BP has a crucial role in controlling tumorigenesis and epithelial cell proliferation in the colon. IL-22BP is highly expressed by dendritic cells in the colon in steady-state conditions. Sensing of intestinal tissue damage via the NLRP3 or NLRP6 inflammasomes led to an IL-18-dependent downregulation of IL-22BP, thereby increasing the ratio of IL-22/IL-22BP. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumour development if uncontrolled during the recovery phase. Thus, the IL-22-IL-22BP axis critically regulates intestinal tissue repair and tumorigenesis in the colon.

  10. nArgBP2 as a hub molecule in the etiology of various neuropsychiatric disorders.

    PubMed

    Lee, Sang-Eun; Chang, Sunghoe

    2016-09-01

    Recent studies have strongly implicated postsynaptic scaffolding proteins such as SAPAP3 or Shank3 in the pathogenesis of various mood disorders, including autism spectrum disorder, bipolar disorder (BD), and obsessive-compulsive disorders. Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that interacts with SAPAP3 and Shank3. Recent study shows that the genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behavior resembling symptoms of BD. However, the function of nArgBP2 at synapse, or its connection with the synaptic dysfunctions, is completely unknown. This study provides compelling evidence that nArgBP2 regulates the spine morphogenesis through the activation of Rac1/WAVE/PAK/cofilin pathway, and that its ablation causes a robust and selective inhibition of excitatory synapse formation, by controlling actin dynamics. Our results revealed the underlying mechanism for the synaptic dysfunction caused by nArgBP2 downregulation that associates with analogous human BD. Moreover, since nArgBP2 interacts with key proteins involved in various neuropsychiatric disorders, our finding implies that nArgBP2 could function as a hub linking various etiological factors of different mood disorders. [BMB Reports 2016; 49(9): 457-458]. PMID:27530683

  11. YB-1 regulates stress granule formation and tumor progression by translationally activating G3BP1

    PubMed Central

    Somasekharan, Syam Prakash; El-Naggar, Amal; Leprivier, Gabriel; Cheng, Hongwei; Hajee, Shamil; Grunewald, Thomas G.P.; Zhang, Fan; Ng, Tony; Delattre, Olivier; Evdokimova, Valentina; Wang, Yuzhuo; Gleave, Martin

    2015-01-01

    Under cell stress, global protein synthesis is inhibited to preserve energy. One mechanism is to sequester and silence mRNAs in ribonucleoprotein complexes known as stress granules (SGs), which contain translationally silent mRNAs, preinitiation factors, and RNA-binding proteins. Y-box binding protein 1 (YB-1) localizes to SGs, but its role in SG biology is unknown. We now report that YB-1 directly binds to and translationally activates the 5′ untranslated region (UTR) of G3BP1 mRNAs, thereby controlling the availability of the G3BP1 SG nucleator for SG assembly. YB-1 inactivation in human sarcoma cells dramatically reduces G3BP1 and SG formation in vitro. YB-1 and G3BP1 expression are highly correlated in human sarcomas, and elevated G3BP1 expression correlates with poor survival. Finally, G3BP1 down-regulation in sarcoma xenografts prevents in vivo SG formation and tumor invasion, and completely blocks lung metastasis in mouse models. Together, these findings demonstrate a critical role for YB-1 in SG formation through translational activation of G3BP1, and highlight novel functions for SGs in tumor progression. PMID:25800057

  12. Dose Limits for Man do not Adequately Protect the Ecosystem

    SciTech Connect

    Higley, Kathryn A.; Alexakhin, Rudolf M.; McDonald, Joseph C.

    2004-08-01

    It has been known for quite some time that different organisms display differing degrees of sensitivity to the effects of ionizing radiations. Some microorganisms such as the bacterium Micrococcus radiodurans, along with many species of invertebrates, are extremely radio-resistant. Humans might be categorized as being relatively sensitive to radiation, and are a bit more resistant than some pine trees. Therefore, it could be argued that maintaining the dose limits necessary to protect humans will also result in the protection of most other species of flora and fauna. This concept is usually referred to as the anthropocentric approach. In other words, if man is protected then the environment is also adequately protected. The ecocentric approach might be stated as; the health of humans is effectively protected only when the environment is not unduly exposed to radiation. The ICRP is working on new recommendations dealing with the protection of the environment, and this debate should help to highlight a number of relevant issues concerning that topic.

  13. DARHT - an `adequate` EIS: A NEPA case study

    SciTech Connect

    Webb, M.D.

    1997-08-01

    The Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility Environmental Impact Statement (EIS) provides a case study that is interesting for many reasons. The EIS was prepared quickly, in the face of a lawsuit, for a project with unforeseen environmental impacts, for a facility that was deemed urgently essential to national security. Following judicial review the EIS was deemed to be {open_quotes}adequate.{close_quotes} DARHT is a facility now being built at Los Alamos National Laboratory (LANL) as part of the Department of Energy (DOE) nuclear weapons stockpile stewardship program. DARHT will be used to evaluate the safety and reliability of nuclear weapons, evaluate conventional munitions and study high-velocity impact phenomena. DARHT will be equipped with two accelerator-driven, high-intensity X-ray machines to record images of materials driven by high explosives. DARHT will be used for a variety of hydrodynamic tests, and DOE plans to conduct some dynamic experiments using plutonium at DARHT as well.

  14. ENSURING ADEQUATE SAFETY WHEN USING HYDROGEN AS A FUEL

    SciTech Connect

    Coutts, D

    2007-01-22

    Demonstration projects using hydrogen as a fuel are becoming very common. Often these projects rely on project-specific risk evaluations to support project safety decisions. This is necessary because regulations, codes, and standards (hereafter referred to as standards) are just being developed. This paper will review some of the approaches being used in these evolving standards, and techniques which demonstration projects can implement to bridge the gap between current requirements and stakeholder desires. Many of the evolving standards for hydrogen-fuel use performance-based language, which establishes minimum performance and safety objectives, as compared with prescriptive-based language that prescribes specific design solutions. This is being done for several reasons including: (1) concern that establishing specific design solutions too early will stifle invention, (2) sparse performance data necessary to support selection of design approaches, and (3) a risk-adverse public which is unwilling to accept losses that were incurred in developing previous prescriptive design standards. The evolving standards often contain words such as: ''The manufacturer shall implement the measures and provide the information necessary to minimize the risk of endangering a person's safety or health''. This typically implies that the manufacturer or project manager must produce and document an acceptable level of risk. If accomplished using comprehensive and systematic process the demonstration project risk assessment can ease the transition to widespread commercialization. An approach to adequately evaluate and document the safety risk will be presented.

  15. Quantifying variability within water samples: the need for adequate subsampling.

    PubMed

    Donohue, Ian; Irvine, Kenneth

    2008-01-01

    Accurate and precise determination of the concentration of nutrients and other substances in waterbodies is an essential requirement for supporting effective management and legislation. Owing primarily to logistic and financial constraints, however, national and regional agencies responsible for monitoring surface waters tend to quantify chemical indicators of water quality using a single sample from each waterbody, thus largely ignoring spatial variability. We show here that total sample variability, which comprises both analytical variability and within-sample heterogeneity, of a number of important chemical indicators of water quality (chlorophyll a, total phosphorus, total nitrogen, soluble molybdate-reactive phosphorus and dissolved inorganic nitrogen) varies significantly both over time and among determinands, and can be extremely high. Within-sample heterogeneity, whose mean contribution to total sample variability ranged between 62% and 100%, was significantly higher in samples taken from rivers compared with those from lakes, and was shown to be reduced by filtration. Our results show clearly that neither a single sample, nor even two sub-samples from that sample is adequate for the reliable, and statistically robust, detection of changes in the quality of surface waters. We recommend strongly that, in situations where it is practicable to take only a single sample from a waterbody, a minimum of three sub-samples are analysed from that sample for robust quantification of both the concentrations of determinands and total sample variability. PMID:17706740

  16. Asiago spectroscopic classification of ASASSN-16bp

    NASA Astrophysics Data System (ADS)

    Tomasella, L.; Pastorello, A.; Benetti, S.; Cappellaro, E.; Elias-Rosa, N.; Ochner, P.; Tartaglia, L.; Terreran, G.; Turatto, M.

    2016-02-01

    The Asiago Transient Classification Program (Tomasella et al. 2014, AN, 335, 841) reports the spectroscopic classification of ASASSN-16bp ( = AT 2016adq), discovered by All Sky Automated Survey for SuperNovae ASAS-SN (see Shappee et al. 2014, ApJ, 788, 48 and http://www.astronomy.ohio-state.edu/~assassin/index.shtml ), in CGCG 336-041 (Atel #8666) The observation was performed with the Asiago 1.82 m Copernico Telescope (+AFOSC; range 340-820 nm; resolution 1.4 nm). Name | Discovery UT | Obs. Date UT |z | Type | Phase |Notes ASASSN-16bp | 20160209.61 | 20160211.11 |0.034194 | Ia | ~10d | (1) (1) Also known as SN2016adq in CGCG 336-041 (z=0.034194, d=145 Mpc, via NED).

  17. On Adequate Comparisons of Antenna Phase Center Variations

    NASA Astrophysics Data System (ADS)

    Schoen, S.; Kersten, T.

    2013-12-01

    One important part for ensuring the high quality of the International GNSS Service's (IGS) products is the collection and publication of receiver - and satellite antenna phase center variations (PCV). The PCV are crucial for global and regional networks, since they introduce a global scale factor of up to 16ppb or changes in the height component with an amount of up to 10cm, respectively. Furthermore, antenna phase center variations are also important for precise orbit determination, navigation and positioning of mobile platforms, like e.g. the GOCE and GRACE gravity missions, or for the accurate Precise Point Positioning (PPP) processing. Using the EUREF Permanent Network (EPN), Baire et al. (2012) showed that individual PCV values have a significant impact on the geodetic positioning. The statements are further supported by studies of Steigenberger et al. (2013) where the impact of PCV for local-ties are analysed. Currently, there are five calibration institutions including the Institut für Erdmessung (IfE) contributing to the IGS PCV file. Different approaches like field calibrations and anechoic chamber measurements are in use. Additionally, the computation and parameterization of the PCV are completely different within the methods. Therefore, every new approach has to pass a benchmark test in order to ensure that variations of PCV values of an identical antenna obtained from different methods are as consistent as possible. Since the number of approaches to obtain these PCV values rises with the number of calibration institutions, there is the necessity for an adequate comparison concept, taking into account not only the numerical values but also stochastic information and computational issues of the determined PCVs. This is of special importance, since the majority of calibrated receiver antennas published by the IGS origin from absolute field calibrations based on the Hannover Concept, Wübbena et al. (2000). In this contribution, a concept for the adequate

  18. Are women with psychosis receiving adequate cervical cancer screening?

    PubMed Central

    Tilbrook, Devon; Polsky, Jane; Lofters, Aisha

    2010-01-01

    ABSTRACT OBJECTIVE To investigate the rates of cervical cancer screening among female patients with psychosis compared with similar patients without psychosis, as an indicator of the quality of primary preventive health care. DESIGN A retrospective cohort study using medical records between November 1, 2004, and November 1, 2007. SETTING Two urban family medicine clinics associated with an academic hospital in Toronto, Ont. PARTICIPANTS A random sample of female patients with and without psychosis between the ages of 20 and 69 years. MAIN OUTCOME MEASURES Number of Papanicolaou tests in a 3-year period. RESULTS Charts for 51 female patients with psychosis and 118 female patients without psychosis were reviewed. Of those women with psychosis, 62.7% were diagnosed with schizophrenia, 19.6% with bipolar disorder, 17.6% with schizoaffective disorder, and 29.4% with other psychotic disorders. Women in both groups were similar in age, rate of comorbidities, and number of full physical examinations. Women with psychosis were significantly more likely to smoke (P < .0001), to have more primary care appointments (P = .035), and to miss appointments (P = .0002) than women without psychosis. After adjustment for age, other psychiatric illnesses, number of physical examinations, number of missed appointments, and having a gynecologist, women with psychosis were significantly less likely to have had a Pap test in the previous 3 years compared with women without psychosis (47.1% vs 73.7%, respectively; odds ratio 0.19, 95% confidence interval 0.06 to 0.58). CONCLUSION Women with psychosis are more than 5 times less likely to receive adequate Pap screening compared with the general population despite their increased rates of smoking and increased number of primary care visits. PMID:20393098

  19. Determining Adequate Margins in Head and Neck Cancers: Practice and Continued Challenges.

    PubMed

    Williams, Michelle D

    2016-09-01

    Margin assessment remains a critical component of oncologic care for head and neck cancer patients. As an integrated team, both surgeons and pathologists work together to assess margins in these complex patients. Differences in method of margin sampling can impact obtainable information and effect outcomes. Additionally, what distance is an "adequate or clear" margin for patient care continues to be debated. Ultimately, future studies and potentially secondary modalities to augment pathologic assessment of margin assessment (i.e., in situ imaging or molecular assessment) may enhance local control in head and neck cancer patients. PMID:27469263

  20. RanBP9 at the intersection between cofilin and Aβ pathologies: rescue of neurodegenerative changes by RanBP9 reduction

    PubMed Central

    Woo, J A; Boggess, T; Uhlar, C; Wang, X; Khan, H; Cappos, G; Joly-Amado, A; De Narvaez, E; Majid, S; Minamide, L S; Bamburg, J R; Morgan, D; Weeber, E; Kang, D E

    2015-01-01

    Molecular pathways underlying the neurotoxicity and production of amyloid β protein (Aβ) represent potentially promising therapeutic targets for Alzheimer's disease (AD). We recently found that overexpression of the scaffolding protein RanBP9 increases Aβ production in cell lines and in transgenic mice while promoting cofilin activation and mitochondrial dysfunction. Translocation of cofilin to mitochondria and induction of cofilin–actin pathology require the activation/dephosphorylation of cofilin by Slingshot homolog 1 (SSH1) and cysteine oxidation of cofilin. In this study, we found that endogenous RanBP9 positively regulates SSH1 levels and mediates Aβ-induced translocation of cofilin to mitochondria and induction of cofilin–actin pathology in cultured cells, primary neurons, and in vivo. Endogenous level of RanBP9 was also required for Aβ-induced collapse of growth cones in immature neurons (days in vitro 9 (DIV9)) and depletion of synaptic proteins in mature neurons (DIV21). In vivo, amyloid precursor protein (APP)/presenilin-1 (PS1) mice exhibited 3.5-fold increased RanBP9 levels, and RanBP9 reduction protected against cofilin–actin pathology, synaptic damage, gliosis, and Aβ accumulation associated with APP/PS1 mice. Brains slices derived from APP/PS1 mice showed significantly impaired long-term potentiation (LTP), and RanBP9 reduction significantly enhanced paired pulse facilitation and LTP, as well as partially rescued contextual memory deficits associated with APP/PS1 mice. Therefore, these results underscore the critical importance of endogenous RanBP9 not only in Aβ accumulation but also in mediating the neurotoxic actions of Aβ at the level of synaptic plasticity, mitochondria, and cofilin–actin pathology via control of the SSH1-cofilin pathway in vivo. PMID:25741591

  1. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

    PubMed Central

    Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

    2015-01-01

    Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. PMID:26283799

  2. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells.

    PubMed

    Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob; Oestergaard, Vibe H; Lisby, Michael

    2015-08-17

    Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis.

  3. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... access. Proper control of personal data in any form associated with automated data systems shall be... persons within or outside the Board. (2) Access to and use of a system of records shall be permitted only..., access to records within a system of records shall be permitted only to the individual to whom the...

  4. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... access. Proper control of personal data in any form associated with automated data systems shall be... persons within or outside the Board. (2) Access to and use of a system of records shall be permitted only..., access to records within a system of records shall be permitted only to the individual to whom the...

  5. Achieving adequate BMP`s for stormwater quality management

    SciTech Connect

    Jones-Lee, A.; Lee, G.F.

    1994-12-31

    There is considerable controversy about the technical appropriateness and the cost-effectiveness of requiring cities to control contaminants in urban stormwater discharges to meet state water quality standards equivalent to US EPA numeric chemical water quality criteria. At this time and likely for the next 10 years, urban stormwater discharges will be exempt from regulation to achieve state water quality standards in receiving waters, owing to the high cost to cities of the management of contaminants in the stormwater runoff-discharge so as to prevent exceedances of water quality standards in the receiving waters. Instead of requiring the same degree of contaminant control for stormwater discharges as is required for point-source discharges of municipal and industrial wastewaters, those responsible for urban stormwater discharges will have to implement Best Management Practices (BMP`s) for contaminant control. The recommended approach for implementation of BMP`s involves the use of site-specific evaluations of what, if any, real problems (use impairment) are caused by stormwater-associated contaminants in the waters receiving that stormwater discharge. From this type of information BMP`s can then be developed to control those contaminants in stormwater discharges that are, in fact, impairing the beneficial uses of receiving waters.

  6. Nephrotoxicity of selectively deuterated and methylated analogues of Tris-BP and Bis-BP in the rat.

    PubMed

    Søderlund, E J; Omichinski, J G; Dahl, J E; Nelson, S D; Dybing, E

    1988-03-01

    Selectively deuterated and methylated analogues of the flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) and its nephrotoxic metabolite bis(2,3-dibromopropyl)phosphate (Bis-BP) were compared to Tris-BP and Bis-BP in inducing acute renal damage in rats. None of the deuterated Tris-BP or Bis-BP analogues significantly altered morphological evidence of nephrotoxicity compared to the protio compounds. On the other hand, some of the selectively methylated analogues were much less nephrotoxic. Although the C1-methyl analogues of both Tris-BP and Bis-BP were as potent nephrotoxicants as Tris-BP and Bis-BP, respectively, neither the C2-methyl nor the C3-methyl analogues were significantly nephrotoxic. Interestingly, whereas the 3,4-dibromobutyl homologue of Tris-BP was not nephrotoxic, the corresponding 3,4-dibromobutyl-Bis homologue was as nephrotoxic as Bis-BP. Additional investigations with treatments that are known to decrease nephrotoxicity caused by several halogenated alkenes, showed that L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) and aminooxyacetic acid were without effects on Tris-BP induced renal damage. Probenecid pretreatment led to a reduction in Tris-BP and Bis-BP tubular necrosis, these effects may be related to inhibition of Bis-BP uptake in the kidney. It appears that the cysteine conjugate beta-lyase pathway is not involved in the generation of nephrotoxic metabolites of Tris-BP. PMID:3375186

  7. Transgenic Expression of Ad4BP/SF-1 in Fetal Adrenal Progenitor Cells Leads to Ectopic Adrenal Formation

    PubMed Central

    Zubair, Mohamad; Oka, Sanae; Parker, Keith L.; Morohashi, Ken-ichirou

    2009-01-01

    Deficiency of adrenal 4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1; NR5A1) impairs adrenal development in a dose-dependent manner, whereas overexpression of Ad4BP/SF-1 is associated with adrenocortical tumorigenesis. Despite its essential roles in adrenal development, the mechanism(s) by which Ad4BP/SF-1 regulates this process remain incompletely understood. We previously identified a fetal adrenal enhancer (FAdE) that stimulates Ad4BP/SF-1 expression in the fetal adrenal gland by a two-step mechanism in which homeobox proteins initiate Ad4BP/SF-1 expression, which then maintains FAdE activity in an autoregulatory loop. In the present study, we examined the effect of transgenic expression of Ad4BP/SF-1 controlled by FAdE on adrenal development. When Ad4BP/SF-1 was overexpressed using a FAdE-Ad4BP/SF-1 transgene, FAdE activity expanded outside of its normal field, resulting in increased adrenal size and the formation of ectopic adrenal tissue in the thorax. The increased size of the adrenal gland did not result from a corresponding increase in cell proliferation, suggesting rather that the increased levels of Ad4BP/SF-1 may divert uncommitted precursors to the steroidogenic lineage. The effects of FAdE-controlled Ad4BP/SF-1 overexpression in mice provide a novel model of ectopic adrenal formation that further supports the critical role of Ad4BP/SF-1 in the determination of steroidogenic cell fate in vivo. PMID:19628584

  8. RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation

    PubMed Central

    Palanichamy, Jayanth Kumar; Tran, Tiffany M.; Howard, Jonathan M.; Contreras, Jorge R.; Fernando, Thilini R.; Sterne-Weiler, Timothy; Katzman, Sol; Toloue, Masoud; Yan, Weihong; Sanford, Jeremy R.; Rao, Dinesh S.

    2016-01-01

    Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia–rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of IGF2BP3 provided murine BM cells with a strong survival advantage, led to proliferation of hematopoietic stem and progenitor cells, and skewed hematopoietic development to the B cell/myeloid lineage. Cross-link immunoprecipitation and high throughput sequencing uncovered the IGF2BP3-regulated transcriptome, which includes oncogenes MYC and CDK6 as direct targets. IGF2BP3 regulated transcripts via targeting elements within 3′ untranslated regions (3′UTR), and enforced IGF2BP3 expression in mice resulted in enhanced expression of Myc and Cdk6 in BM. Together, our data suggest that IGF2BP3-mediated targeting of oncogenic transcripts may represent a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate RNA-binding partners as potential therapeutic targets in this disease. PMID:26974154

  9. RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation.

    PubMed

    Palanichamy, Jayanth Kumar; Tran, Tiffany M; Howard, Jonathan M; Contreras, Jorge R; Fernando, Thilini R; Sterne-Weiler, Timothy; Katzman, Sol; Toloue, Masoud; Yan, Weihong; Basso, Giuseppe; Pigazzi, Martina; Sanford, Jeremy R; Rao, Dinesh S

    2016-04-01

    Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia-rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of IGF2BP3 provided murine BM cells with a strong survival advantage, led to proliferation of hematopoietic stem and progenitor cells, and skewed hematopoietic development to the B cell/myeloid lineage. Cross-link immunoprecipitation and high throughput sequencing uncovered the IGF2BP3-regulated transcriptome, which includes oncogenes MYC and CDK6 as direct targets. IGF2BP3 regulated transcripts via targeting elements within 3' untranslated regions (3'UTR), and enforced IGF2BP3 expression in mice resulted in enhanced expression of Myc and Cdk6 in BM. Together, our data suggest that IGF2BP3-mediated targeting of oncogenic transcripts may represent a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate RNA-binding partners as potential therapeutic targets in this disease.

  10. Maintaining Adequate CO2 Washout for an Advanced EMU via a New Rapid Cycle Amine Technology

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda; Conger, Bruce

    2012-01-01

    Over the past several years, NASA has realized tremendous progress in Extravehicular Activity (EVA) technology development. This has been evidenced by the progressive development of a new Rapid Cycle Amine (RCA) system for the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support Subsystem (PLSS). The PLSS is responsible for the life support of the crew member in the spacesuit. The RCA technology is responsible for carbon dioxide (CO2) and humidity control. Another aspect of the RCA is that it is on-back vacuum-regenerable, efficient, and reliable. The RCA also simplifies the PLSS schematic by eliminating the need for a condensing heat exchanger for humidity control in the current EMU. As development progresses on the RCA, it is important that the sizing be optimized so that the demand on the PLSS battery is minimized. As well, maintaining the CO2 washout at adequate levels during an EVA is an absolute requirement of the RCA and associated ventilation system. Testing has been underway in-house at NASA Johnson Space Center and analysis has been initiated to evaluate whether the technology provides exemplary performance in ensuring that the CO2 is removed sufficiently and the ventilation flow is adequate for maintaining CO2 washout in the AEMU spacesuit helmet of the crew member during an EVA. This paper will review the recent developments of the RCA unit, testing planned in-house with a spacesuit simulator, and the associated analytical work along with insights from the medical aspect on the testing. 1

  11. Are Substance Use Prevention Programs More Effective in Schools Making Adequate Yearly Progress? A Study of Project ALERT

    ERIC Educational Resources Information Center

    Clark, Heddy Kovach; Ringwalt, Chris L.; Shamblen, Stephen R.; Hanley, Sean M.; Flewelling, Robert L.

    2011-01-01

    This exploratory study sought to determine if a popular school-based drug prevention program might be effective in schools that are making adequate yearly progress (AYP). Thirty-four schools with grades 6 through 8 in 11 states were randomly assigned either to receive Project ALERT (n = 17) or to a control group (n = 17); of these, 10 intervention…

  12. Placement of the GaBP ring system in the banded gastric bypass operation.

    PubMed

    Fobi, Mathias A L

    2005-09-01

    Currently, bariatric surgeons fashion the band or ring reinforcement prosthesis, to control the stoma in the vertical banded gastroplasty and gastric bypass operations for morbid obesity. To meet this need, the GaBP Ring system has been developed in various sizes, and consists of 4 main parts to provide a means for inserting a ring around the gastric pouch in the banded gastric bypass or the vertical banded gastroplasty. The pre-manufactured and sterilized device provides for better standardization and quality control than individually surgeon-fashioned devices. The GaBP Ring system is described, and the technique of placement and the pertinent initial clinical results are presented. PMID:16197796

  13. Phase 1 remedial investigation report for 200-BP-1 operable unit. Volume 1

    SciTech Connect

    Not Available

    1993-09-01

    The US Department of Energy (DOE) Hanford Site, in Washington State is organized into numerically designated operational areas including the 100, 200, 300, 400, 600, and 1100 Areas. The US Environmental Protection Agency (EPA), in November 1989 included the 200 Areas of the Hanford Site on the National Priority List (NPL) under the Comprehensive Environmental Response, Compensation and Liability Act of 1980 (CERCLA). Inclusion on the NPL initiated the remedial investigation (RD process for the 200-BP-1 operable unit. These efforts are being addressed through the Hanford Federal Facility Agreement and Consent Order (Ecology et al. 1989) which was negotiated and approved by the DOE, the EPA, and the State of Washington Department of Ecology (Ecology) in May 1989. This agreement, known as the Tri-Party Agreement, governs all CERCLA efforts at Hanford. In March of 1990, the Department of Energy, Richland Operations (DOE-RL) issued a Remedial Investigation/Feasibility Study (RI/FS) work plan (DOE-RL 1990a) for the 200-BP-1 operable unit. The work plan initiated the first phase of site characterization activities associated with the 200-BP-1 operable unit. The purpose of the 200-BP-1 operable unit RI is to gather and develop the necessary information to adequately understand the risks to human health and the environment posed by the site and to support the development and analysis of remedial alternatives during the FS. The RI analysis will, in turn, be used by Tri-Party Agreement signatories to make a risk-management-based selection of remedies for the releases of hazardous substances that have occurred from the 200-BP-1 operable unit.

  14. Advanced pancreatic cancer - how to choose an adequate treatment option

    PubMed Central

    Korkeila, Eija A

    2015-01-01

    The prognosis of pancreatic adenocarcinoma is poor, making it one of the leading causes of cancer-related death. The 5-year overall survival rate remains below 5% and little progress is made during the past decade. Only about 10%-20% of patients are eligible for curative-intent surgery and the majority end up having recurring disease even after radical surgery and postoperative adjuvant chemotherapy. Chemotherapy in metastatic disease is palliative at best, aiming at disease and symptom control and prolongation of life. Treatment always causes side effects, the degree of which varies from patient to patient, depending on the patient’s general condition, concomitant morbidities as well as on the chosen treatment modality. Why is pancreatic cancer so resistant to treatment? How to best help the patient to reach the set treatment goals? PMID:26478662

  15. The Importance of Adequate Iodine during Pregnancy and Infancy.

    PubMed

    Zimmermann, Michael B

    2016-01-01

    Iodine requirements are increased ≥50% during pregnancy. Iodine deficiency during pregnancy can cause maternal and fetal hypothyroidism and impair neurological development of the fetus. The consequences depend upon the timing and severity of the hypothyroidism; the most severe manifestation is cretinism. In iodine-deficient areas, controlled studies have demonstrated that iodine supplementation before or during early pregnancy eliminates new cases of cretinism, increases birth weight, reduces rates of perinatal and infant mortality and generally increases developmental scores in young children by 10-20%. Mild-to-moderate maternal iodine deficiency can cause thyroid dysfunction, but whether it impairs cognitive and/or neurological function in the offspring remains uncertain. In nearly all regions affected by iodine deficiency, salt iodization is the most cost-effective way of delivering iodine and improving maternal and infant health. PMID:27198746

  16. Are the current Australian sun exposure guidelines effective in maintaining adequate levels of 25-hydroxyvitamin D?

    PubMed

    Kimlin, Michael; Sun, Jiandong; Sinclair, Craig; Heward, Sue; Hill, Jane; Dunstone, Kimberley; Brodie, Alison

    2016-01-01

    An adequate vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D) concentration, is important in humans for maintenance of healthy bones and muscle function. Serum 25(OH)D concentration was assessed in participants from Melbourne, Australia (37.81S, 144.96E), who were provided with the current Australian guidelines on sun exposure for 25(OH)D adequacy (25(OH)D ≥50 nmol/L). Participants were interviewed in February (summer, n=104) and August (winter, n=99) of 2013. Serum 25(OH)D concentration was examined as a function of measures of sun exposure and sun protection habits with control of key characteristics such as dietary intake of vitamin D, body mass index (BMI) and skin colour, that may modify this relationship. The mean 25(OH)D concentration in participants who complied with the current sun exposure guidelines was 67.3 nmol/L in summer and 41.9 nmol/L in winter. At the end of the study, 69.3% of participants who complied with the summer sun exposure guidelines were 25(OH)D adequate, while only 27.6% of participants who complied with the winter sun exposure guidelines were 25(OH)D adequate at the end of the study. The results suggest that the current Australian guidelines for sun exposure for 25(OH)D adequacy are effective for most in summer and ineffective for most in winter. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  17. [Are legal sanctions for improving traffic safety adequate?].

    PubMed

    Geppert, K

    1990-01-01

    Referring to the field of traffic legislation the author examines the different possibilities to improve the safety on the road, within the corresponding range of summary offence and criminal law; (1) As far as the rules of conduct are concerned he demands a uniform threshold value of at least 0.8% for blood alcohol within the limits of the German penal code Sections 315 c I, 316. He rejects the plan to introduce a criminal offence of considerable speeding if imminent danger is provoked. (2) On the level of sanctions the traditional measures of traffic legislation are to be supplied sensibly by supplementary training courses concerning alcohol abuse. The legal instruments of (temporary) suspension of a person's driving license on the part of criminal jurisdiction or public authorities ought to be utilized on a larger scale. The (Flensburg) repeated perpetration point system is to be improved with regard to special preventive measures. (3) To increase the risk of being caught the control of the traffic by the police is to be intensified--especially through a larger application of technical means. (4) The extension of the instruments of traffic legislation to immediate measures by the police--preliminary or "mini" suspension of a person's driving license by resort to preventive rights by the police?--meets with constitutional or legal scruples.

  18. Is the Australian hospital system adequately prepared for terrorism?

    PubMed

    Rosenfeld, Jeffrey V; Fitzgerald, Mark; Kossmann, Thomas; Pearce, Andrew; Joseph, Anthony; Joseph, Andrew; Tan, Gim; Gardner, Michele; Shapira, Shmuel

    Australian hospitals need to be prepared to deal with mass casualties from terrorist strikes, including bomb blasts and chemical, biological and radiation injury. Injuries from bomb explosions are more severe than those commonly seen in Australian hospitals. In disasters involving mass casualties in urban areas, many of the injured make their own way to hospital, often arriving before the more seriously injured casualties. Major hospitals in Australia should plan for large numbers of undifferentiated and potentially contaminated casualties arriving with minimal warning. It is critical that experienced and trained senior medical officers perform the triage of casualties in emergency departments, with frequent reassessment to detect missed injuries (especially pulmonary blast injury). Hospitals require well developed standard operating procedures for mass casualty events, reinforced by regular drills. Preparing for a major event includes training staff in major incident management, setting up an operational/control unit, nominating key personnel, ensuring there is an efficient intra-hospital communication system, and enhancing links with other emergency services and hospitals. PMID:16336131

  19. Are hotspots of evolutionary potential adequately protected in southern California?

    USGS Publications Warehouse

    Vandergast, A.G.; Bohonak, A.J.; Hathaway, S.A.; Boys, J.; Fisher, R.N.

    2008-01-01

    Reserves are often designed to protect rare habitats, or "typical" exemplars of ecoregions and geomorphic provinces. This approach focuses on current patterns of organismal and ecosystem-level biodiversity, but typically ignores the evolutionary processes that control the gain and loss of biodiversity at these and other levels (e.g., genetic, ecological). In order to include evolutionary processes in conservation planning efforts, their spatial components must first be identified and mapped. We describe a GIS-based approach for explicitly mapping patterns of genetic divergence and diversity for multiple species (a "multi-species genetic landscape"). Using this approach, we analyzed mitochondrial DNA datasets from 21 vertebrate and invertebrate species in southern California to identify areas with common phylogeographic breaks and high intrapopulation diversity. The result is an evolutionary framework for southern California within which patterns of genetic diversity can be analyzed in the context of historical processes, future evolutionary potential and current reserve design. Our multi-species genetic landscapes pinpoint six hotspots where interpopulation genetic divergence is consistently high, five evolutionary hotspots within which genetic connectivity is high, and three hotspots where intrapopulation genetic diversity is high. These 14 hotspots can be grouped into eight geographic areas, of which five largely are unprotected at this time. The multi-species genetic landscape approach may provide an avenue to readily incorporate measures of evolutionary process into GIS-based systematic conservation assessment and land-use planning.

  20. RanBP9 Overexpression Accelerates Loss of Dendritic Spines in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Wang, Ruizhi; Palavicini, Juan Pablo; Wang, Hongjie; Maiti, Panchanan; Bianchi, Elisabetta; Xu, Shaohua; Lloyd, BN; Dawson-Scully, Ken; Kang, David E; Lakshmana, Madepalli K.

    2014-01-01

    We previously demonstrated that RanBP9 overexpression increased Aβ generation and amyloid plaque burden, subsequently leading to robust reductions in the levels of several synaptic proteins as well as deficits in the learning and memory skills in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin-immunoreactive puncta (52%, p<0.001) and spinophilin area (62.5%, p<0.001) in the primary cortical neurons derived from RanBP9 transgenic mice (RanBP9-Tg) compared to wild-type (WT) neurons. Similar results were confirmed in WT cortical neurons transfected with EGFP-RanBP9. At 6-months of age, the total spine density in the cortex of RanBP9 single transgenic, APΔE9 double transgenic and APΔE9/RanBP9 triple transgenic mice were similar to WT mice. However, in the hippocampus the spine density was significantly reduced (27%, p<0.05) in the triple transgenic mice compared to WT mice due to reduced number of thin spines (33%, p<0.05) and mushroom spines (22%, p<0.05). This suggests that RanBP9 overexpression in the APΔE9 mice accelerates loss of spines and that hippocampus is more vulnerable. At 12-months of age, cortex showed significant reductions in total spine density in the RanBP9 (22%, p<0.05), APΔE9 (19%, p<0.05) and APΔE9/RanBP9 (33%, p<0.01) mice compared to WT controls due to reductions in mushroom and thin spines. Similarly, in the hippocampus the total spine density was reduced in the RanBP9 (23%, p<0.05), APΔE9 (26%, p<0.05) and APΔE9/RanBP9 (39%, p<0.01) mice due to reductions in thin and mushroom spines. Most importantly, RanBP9 overexpression in the APΔE9 mice further exacerbated the reductions in spine density in both the cortex (14%, p<0.05) and the hippocampus (16%, p<0.05). Because dendritic spines are considered physical traces of memory, loss of spines due to RanBP9 provided the physical basis for the learning and memory deficits. Since RanBP9 protein levels are increased in AD brains, RanBP

  1. RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of Alzheimer's disease.

    PubMed

    Wang, Ruizhi; Palavicini, Juan Pablo; Wang, Hongjie; Maiti, Panchanan; Bianchi, Elisabetta; Xu, Shaohua; Lloyd, B N; Dawson-Scully, Ken; Kang, David E; Lakshmana, Madepalli K

    2014-09-01

    We previously demonstrated that RanBP9 overexpression increased Aβ generation and amyloid plaque burden, subsequently leading to robust reductions in the levels of several synaptic proteins as well as deficits in the learning and memory skills in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin-immunoreactive puncta (52%, p<0.001) and spinophilin area (62.5%, p<0.001) in the primary cortical neurons derived from RanBP9 transgenic mice (RanBP9-Tg) compared to wild-type (WT) neurons. Similar results were confirmed in WT cortical neurons transfected with EGFP-RanBP9. At 6-months of age, the total spine density in the cortex of RanBP9 single transgenic, APΔE9 double transgenic and APΔE9/RanBP9 triple transgenic mice was similar to WT mice. However, in the hippocampus the spine density was significantly reduced (27%, p<0.05) in the triple transgenic mice compared to WT mice due to reduced number of thin spines (33%, p<0.05) and mushroom spines (22%, p<0.05). This suggests that RanBP9 overexpression in the APΔE9 mice accelerates loss of spines and that the hippocampus is more vulnerable. At 12-months of age, the cortex showed significant reductions in total spine density in the RanBP9 (22%, p<0.05), APΔE9 (19%, p<0.05) and APΔE9/RanBP9 (33%, p<0.01) mice compared to WT controls due to reductions in mushroom and thin spines. Similarly, in the hippocampus the total spine density was reduced in the RanBP9 (23%, p<0.05), APΔE9 (26%, p<0.05) and APΔE9/RanBP9 (39%, p<0.01) mice due to reductions in thin and mushroom spines. Most importantly, RanBP9 overexpression in the APΔE9 mice further exacerbated the reductions in spine density in both the cortex (14%, p<0.05) and the hippocampus (16%, p<0.05). Because dendritic spines are considered physical traces of memory, loss of spines due to RanBP9 provided the physical basis for the learning and memory deficits. Since RanBP9 protein levels are increased in AD

  2. The Stress Granule Protein G3BP1 Recruits Protein Kinase R To Promote Multiple Innate Immune Antiviral Responses

    PubMed Central

    Reineke, Lucas C.

    2014-01-01

    ABSTRACT Stress granules (SGs) are cytoplasmic storage sites containing translationally silenced mRNPs that can be released to resume translation after stress subsides. We previously showed that poliovirus 3C proteinase cleaves the SG-nucleating protein G3BP1, blocking the ability of cells to form SGs late in infection. Many other viruses also target G3BP1 and inhibit SG formation, but the reasons why these functions evolved are unclear. Previously, we also showed a link between G3BP1-induced SGs and protein kinase R (PKR)-mediated translational control, but the mechanism of PKR interplay with SG and the antiviral consequences are unknown. Here, we show that G3BP1 exhibits antiviral activity against several enteroviruses, whereas truncated G3BP1 that cannot form SGs does not. G3BP1-induced SGs are linked to activation of innate immune transcriptional responses through NF-κB and JNK. The G3BP1-induced SGs also recruit PKR and other antiviral proteins. We show that the PXXP domain within G3BP1 is essential for the recruitment of PKR to SGs, for eIF2α phosphorylation driven by PKR, and for nucleating SGs of normal composition. We also show that deletion of the PXXP domain in G3BP1 compromises its antiviral activity. These findings tie PKR activation to its recruitment to SGs by G3BP1 and indicate that G3BP1 promotes innate immune responses at both the transcriptional and translational levels and integrates cellular stress responses and innate immunity. IMPORTANCE Stress granules appear during virus infection, and their importance is not well understood. Previously, it was assumed that they were nonfunctional artifacts associated with cellular stress. PKR is a well-known antiviral protein; however, its regulation in cells is not well understood. Our work links cellular stress granules with activation of PKR and other innate immune pathways through the activity of G3BP1, a critical stress granule component. The ability of stress granules and G3BP1 to activate PKR and

  3. Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging.

    PubMed

    Neuner, Sarah M; Garfinkel, Benjamin P; Wilmott, Lynda A; Ignatowska-Jankowska, Bogna M; Citri, Ami; Orly, Joseph; Lu, Lu; Overall, Rupert W; Mulligan, Megan K; Kempermann, Gerd; Williams, Robert W; O'Connell, Kristen M S; Kaczorowski, Catherine C

    2016-10-01

    An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we identify Hp1bp3 as a novel modulator of cognitive aging using a genetically diverse population of mice and confirm that HP1BP3 protein levels are significantly reduced in the hippocampi of cognitively impaired elderly humans relative to cognitively intact controls. Deletion of functional Hp1bp3 in mice recapitulates memory deficits characteristic of aged impaired mice and humans, further supporting the idea that Hp1bp3 and associated molecular networks are modulators of cognitive aging. Overall, our results suggest Hp1bp3 may serve as a potential target against cognitive aging and demonstrate the utility of genetically diverse animal models for the study of complex human disease. PMID:27460150

  4. Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging.

    PubMed

    Neuner, Sarah M; Garfinkel, Benjamin P; Wilmott, Lynda A; Ignatowska-Jankowska, Bogna M; Citri, Ami; Orly, Joseph; Lu, Lu; Overall, Rupert W; Mulligan, Megan K; Kempermann, Gerd; Williams, Robert W; O'Connell, Kristen M S; Kaczorowski, Catherine C

    2016-10-01

    An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we identify Hp1bp3 as a novel modulator of cognitive aging using a genetically diverse population of mice and confirm that HP1BP3 protein levels are significantly reduced in the hippocampi of cognitively impaired elderly humans relative to cognitively intact controls. Deletion of functional Hp1bp3 in mice recapitulates memory deficits characteristic of aged impaired mice and humans, further supporting the idea that Hp1bp3 and associated molecular networks are modulators of cognitive aging. Overall, our results suggest Hp1bp3 may serve as a potential target against cognitive aging and demonstrate the utility of genetically diverse animal models for the study of complex human disease.

  5. Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP).

    PubMed

    Korwar, Sudha; Morris, Benjamin L; Parikh, Hardik I; Coover, Robert A; Doughty, Tyler W; Love, Ian M; Hilbert, Brendan J; Royer, William E; Kellogg, Glen E; Grossman, Steven R; Ellis, Keith C

    2016-06-15

    C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD(+) as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50=0.24μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50=0.18μM) and 3-chloro- (IC50=0.17μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer.

  6. Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP).

    PubMed

    Korwar, Sudha; Morris, Benjamin L; Parikh, Hardik I; Coover, Robert A; Doughty, Tyler W; Love, Ian M; Hilbert, Brendan J; Royer, William E; Kellogg, Glen E; Grossman, Steven R; Ellis, Keith C

    2016-06-15

    C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD(+) as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50=0.24μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50=0.18μM) and 3-chloro- (IC50=0.17μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer. PMID:27156192

  7. 76 FR 51041 - Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Hemoglobin Standards and Maintaining Adequate Iron Stores in... Standards and Maintaining Adequate Iron Stores in Blood Donors.'' The purpose of this public workshop is to... donor safety and blood availability, and potential measures to maintain adequate iron stores in...

  8. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical devices; adequate directions for use. 801... (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate directions for use. Adequate directions for use means directions under which the layman can use a device...

  9. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  10. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  11. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  12. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE... Preserve Snowmachine (snowmobile) Operations § 13.960 Who determines when there is adequate snow cover? The superintendent will determine when snow cover is adequate for snowmachine use. The superintendent will follow...

  13. Revisiting G3BP1 as a RasGAP Binding Protein: Sensitization of Tumor Cells to Chemotherapy by the RasGAP 317–326 Sequence Does Not Involve G3BP1

    PubMed Central

    Annibaldi, Alessandro; Dousse, Aline; Martin, Sophie; Tazi, Jamal; Widmann, Christian

    2011-01-01

    RasGAP is a multifunctional protein that controls Ras activity and that is found in chromosomal passenger complexes. It also negatively or positively regulates apoptosis depending on the extent of its cleavage by caspase-3. RasGAP has been reported to bind to G3BP1 (RasGAP SH3-domain-binding protein 1), a protein regulating mRNA stability and stress granule formation. The region of RasGAP (amino acids 317–326) thought to bind to G3BP1 corresponds exactly to the sequence within fragment N2, a caspase-3-generated fragment of RasGAP, that mediates sensitization of tumor cells to genotoxins. While assessing the contribution of G3BP1 in the anti-cancer function of a cell-permeable peptide containing the 317–326 sequence of RasGAP (TAT-RasGAP317–326), we found that, in conditions where G3BP1 and RasGAP bind to known partners, no interaction between G3BP1 and RasGAP could be detected. TAT-RasGAP317–326 did not modulate binding of G3BP1 to USP10, stress granule formation or c-myc mRNA levels. Finally, TAT-RasGAP317–326 was able to sensitize G3BP1 knock-out cells to cisplatin-induced apoptosis. Collectively these results indicate that G3BP1 and its putative RasGAP binding region have no functional influence on each other. Importantly, our data provide arguments against G3BP1 being a genuine RasGAP-binding partner. Hence, G3BP1-mediated signaling may not involve RasGAP. PMID:22205990

  14. Revisiting G3BP1 as a RasGAP binding protein: sensitization of tumor cells to chemotherapy by the RasGAP 317-326 sequence does not involve G3BP1.

    PubMed

    Annibaldi, Alessandro; Dousse, Aline; Martin, Sophie; Tazi, Jamal; Widmann, Christian

    2011-01-01

    RasGAP is a multifunctional protein that controls Ras activity and that is found in chromosomal passenger complexes. It also negatively or positively regulates apoptosis depending on the extent of its cleavage by caspase-3. RasGAP has been reported to bind to G3BP1 (RasGAP SH3-domain-binding protein 1), a protein regulating mRNA stability and stress granule formation. The region of RasGAP (amino acids 317-326) thought to bind to G3BP1 corresponds exactly to the sequence within fragment N2, a caspase-3-generated fragment of RasGAP, that mediates sensitization of tumor cells to genotoxins. While assessing the contribution of G3BP1 in the anti-cancer function of a cell-permeable peptide containing the 317-326 sequence of RasGAP (TAT-RasGAP₃₁₇₋₃₂₆), we found that, in conditions where G3BP1 and RasGAP bind to known partners, no interaction between G3BP1 and RasGAP could be detected. TAT-RasGAP₃₁₇₋₃₂₆ did not modulate binding of G3BP1 to USP10, stress granule formation or c-myc mRNA levels. Finally, TAT-RasGAP₃₁₇₋₃₂₆ was able to sensitize G3BP1 knock-out cells to cisplatin-induced apoptosis. Collectively these results indicate that G3BP1 and its putative RasGAP binding region have no functional influence on each other. Importantly, our data provide arguments against G3BP1 being a genuine RasGAP-binding partner. Hence, G3BP1-mediated signaling may not involve RasGAP.

  15. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies.

    PubMed

    Robinson, Jennifer G; Colhoun, Helen M; Bays, Harold E; Jones, Peter H; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

    2014-10-01

    The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20-40 mg/d) or rosuvastatin (10-20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20-40 mg) or rosuvastatin (10-20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level. PMID:25269777

  16. Efficacy and Safety of Alirocumab as Add-on Therapy in High–Cardiovascular-Risk Patients With Hypercholesterolemia Not Adequately Controlled With Atorvastatin (20 or 40 mg) or Rosuvastatin (10 or 20 mg): Design and Rationale of the ODYSSEY OPTIONS Studies

    PubMed Central

    Robinson, Jennifer G; Colhoun, Helen M; Bays, Harold E; Jones, Peter H; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

    2014-01-01

    The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20–40 mg/d) or rosuvastatin (10–20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20–40 mg) or rosuvastatin (10–20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level. PMID:25269777

  17. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies.

    PubMed

    Robinson, Jennifer G; Colhoun, Helen M; Bays, Harold E; Jones, Peter H; Du, Yunling; Hanotin, Corinne; Donahue, Stephen

    2014-10-01

    The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20-40 mg/d) or rosuvastatin (10-20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20-40 mg) or rosuvastatin (10-20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level.

  18. Maintaining Adequate CO2 Washout for an Advanced EMU via a New Rapid Cycle Amine Technology

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda

    2011-01-01

    Over the past several years, NASA has realized tremendous progress in Extravehicular Activity (EVA) technology development. This has been evidenced by the progressive development of a new Rapic Cycle Amine (RCA) system for the Advanced Extravehicular Mobility Unit (AEMU) Portable Life Support Subsystem (PLSS). The PLSS is responsible for the life support of the crew member in the spacesuit. The RCA technology is responsible for carbon dioxide (CO2) and humidity control. Another aspect of the RCA is that it is on-back vacuum-regenerable, efficient, and reliable. The RCA also simplifies the PLSS schematic by eliminating the need for a condensing heat exchanger for humidity control in the current EMU. As development progresses on the RCA, it is important that the sizing be optimized so that the demand on the PLSS battery is minimized. As well, maintaining the CO2 washout at adequate levels during an EVA is an absolute requirement of the RCA and associated ventilation system. Testing has been underway in-house at NASA Johnson Space Center and analysis has been initiated to evaluate whether the technology provides exemplary performance in ensuring that the CO2 is removed sufficiently enough and the ventilation flow is adequate enough to maintain CO2 1 Project Engineer, Space Suit and Crew Survival Systems Branch, Crew and Thermal Systems Division, 2101 NASA Parkway, Houston, TX 77058/EC5. washout in the AEMU spacesuit helmet of the crew member during an EVA. This paper will review the recent developments of the RCA unit, the testing results performed in-house with a spacesuit simulator, and the associated analytical work along with insights from the medical aspect on the testing.

  19. Components of the CtBP1/BARS-dependent fission machinery.

    PubMed

    Valente, Carmen; Luini, Alberto; Corda, Daniela

    2013-10-01

    The brefeldin A ADP-ribosylated substrate, a member of the C-terminal-binding protein family that is referred to as CtBP1/BARS, is a dual-function protein that acts as a transcriptional co-repressor in the nucleus and as an inducer of membrane fission in the cytoplasm. In this review, we first discuss the mechanisms that enable CtBP1/BARS to shift between the nuclear transcriptional co-repressor and the cytosolic fission-inducing activities. Then, we focus on the role of CtBP1/BARS in membrane fission. CtBP1/BARS controls several fission events including macropinocytosis, fluid-phase endocytosis, COPI-coated vesicle formation, basolaterally directed post-Golgi carrier formation, and Golgi partitioning in mitosis. We report on recent advances in our understanding of the CtBP1/BARS membrane fission machineries that operate at the trans-side and at the cis-side of the Golgi complex. Specifically, we discuss how these machineries are assembled and regulated, and how they operate in the formation of the basolaterally directed post-Golgi carriers.

  20. Study on adaptive BTT reentry speed depletion guidance law based on BP neural network

    NASA Astrophysics Data System (ADS)

    Zheng, Zongzhun; Wang, Yongji; Wu, Hao

    2007-11-01

    Reentry guidance is one of the key technologies in hypersonic vehicle research field. In addition to the constraints on its final position coordinates, the vehicle must also impact the target from a specified direction with high precision. And therefore the adaptability of guidance law is critical to control the velocity of hypersonic vehicle and firing accuracy properly in different surroundings of large airspace. In this paper, a new adaptive guidance strategy based on Back Propagation (BP) neural network for the reentry mission of a generic hypersonic vehicle is presented. Depending on the nicer self-learn ability of BP neural network, the guidance law considers the influence of biggish mis-modeling of aerodynamics, structure error and other initial disturbances on the flight capability of vehicle. Consequently, terminal position accuracy and velocity are guaranteed, while many constraints are satisfied. Numerical simulation results clearly bring out the fact that the proposed reentry guidance law based on BP neural network is rational and effective.

  1. Trailer siting issues: BP Texas City.

    PubMed

    Kaszniak, Mark; Holmstrom, Donald

    2008-11-15

    On 23 March, 2005, a series of explosions and fires occurred at the BP Texas City refinery during the startup of an isomerization (ISOM) process unit. Fifteen workers were killed and about 180 others were injured. All of the fatalities were contract workers; the deaths and most of the serious injuries occurred in and around temporary office trailers that had been sited near a blowdown drum and stack open to the atmosphere as part of ongoing turnaround activities in an adjacent unit. Due to problems that developed during the ISOM startup, flammable hydrocarbon liquid overfilled the blowdown drum and stack which resulted in a geyser-like release out the top into the atmosphere. The flammable hydrocarbons fell to the ground releasing vapors that were likely ignited from a nearby idling diesel pickup truck. A total of 44 trailers were damaged by the blast pressure wave that propagated through the refinery when the vapor cloud exploded. Thirteen trailers were totally destroyed and workers were injured in trailers as far as 479ft away from the release. The focus of this paper will be on trailer siting issues, including: need for work/office trailers within process units, adequacy of risk analysis methods in API RP 752, and minimum safe distance requirements

  2. Trailer siting issues: BP Texas City.

    PubMed

    Kaszniak, Mark; Holmstrom, Donald

    2008-11-15

    On 23 March, 2005, a series of explosions and fires occurred at the BP Texas City refinery during the startup of an isomerization (ISOM) process unit. Fifteen workers were killed and about 180 others were injured. All of the fatalities were contract workers; the deaths and most of the serious injuries occurred in and around temporary office trailers that had been sited near a blowdown drum and stack open to the atmosphere as part of ongoing turnaround activities in an adjacent unit. Due to problems that developed during the ISOM startup, flammable hydrocarbon liquid overfilled the blowdown drum and stack which resulted in a geyser-like release out the top into the atmosphere. The flammable hydrocarbons fell to the ground releasing vapors that were likely ignited from a nearby idling diesel pickup truck. A total of 44 trailers were damaged by the blast pressure wave that propagated through the refinery when the vapor cloud exploded. Thirteen trailers were totally destroyed and workers were injured in trailers as far as 479ft away from the release. The focus of this paper will be on trailer siting issues, including: need for work/office trailers within process units, adequacy of risk analysis methods in API RP 752, and minimum safe distance requirements PMID:18294765

  3. High temporal Resolution Fire History in Eastern Africa: the Last 16 kyr cal. BP

    NASA Astrophysics Data System (ADS)

    Vanniere, B.; Carcaillet, C.; Garcin, Y.; Vullien, A.; Williamson, D.

    2004-12-01

    Charcoal series, based on a high temporal resolution analysis, at Lake Massoko (9°20' S, 33° 45' E, 770 a.s.l., SW Tanzania) reveals numerous changes of fire regime over the last 16 kyr cal BP. Data are based on the tallying of charcoal from 700 continuous 1 cm thick samples along a 7m long sequence. The structure of charcoal particles is well preserved with an length:width ratio superior to 5; this appears to testify to the local provenance of the material studied and to the rapid transport of particles to the lake. The majority of particles belongs to herbaceous cuticles produced by savanna or bush fires. Time control is supported by 14 radiocarbon dates. Mean time resolution per sample of 17 yr provides the first long detailed biomass burning record in Africa. This record evidences frequent fires events during the last 16 kyr, indicating that fire is a key component of east African ecosystems since, at least, the last glacial stage up to present. From 16 to 12 kyr cal BP, the charcoal influx into the lake is low except during two specific sequences, between 13.5-12.5 kyr cal BP and 14.5-14 kyr cal BP. These may correspond to more arid or more biomass-available phases. Around 10 kyr cal BP, at the early Holocene a greater influx of charcoal is recorded in the lake, probably as a result of a high fire regime likely triggered by severe droughts. Between 8.3 and 1.7 kyr cal BP, the charcoal influx displays a cyclic fire history of ca. 500 yr. Low fire regime, between 3.5-2.5, 5.5-5 and 7.5-7 kyr cal BP, correspond to wetter periods. About 12 sequences of fire increase and decrease are highlighted, which appears to support a high climatic variability during the middle-Holocene. After 1.7 kyr BP, there is a long lasting increase of charcoal influx into the lake, as observed by black carbon analysis (Thevenon et al., 2003). This particular period, without analog since 16 kyr cal BP, is consistent with the development of Iron Age settlements in the region, slash

  4. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of the Center for Veterinary Medicine (the Director) may, on the Director's own initiative or on the... to the particular study, what alternative procedures, if any, are to be, or have been employed,...

  5. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of the Center for Veterinary Medicine (the Director) may, on the Director's own initiative or on the... to the particular study, what alternative procedures, if any, are to be, or have been employed,...

  6. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the critical characteristics of identity, strength, quality, purity, and physical form of the new... with other studies conducted with the new animal drug. The physical form of a new animal drug includes the formulation and physical characterization (including delivery systems thereof, if any) of the...

  7. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the critical characteristics of identity, strength, quality, purity, and physical form of the new... for special circumstances. Examples include studies in which the effect of the new animal drug is...

  8. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... predictable mortality (for example, certain malignancies) and studies in which the effect of the drug is self... that the test drug be standardized as to identity, strength, quality, purity, and dosage form to...

  9. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... the critical characteristics of identity, strength, quality, purity, and physical form of the new... for special circumstances. Examples include studies in which the effect of the new animal drug is...

  10. Reliable Detection of Respiratory Syncytial Virus Infection in Children for Adequate Hospital Infection Control Management

    PubMed Central

    Abels, Susanne; Nadal, David; Stroehle, Angelika; Bossart, Walter

    2001-01-01

    By using a rapid test for respiratory syncytial virus (RSV) detection (Abbott TestPack RSV), a number of patients were observed, showing repeatedly positive results over a period of up to 10 weeks. A prospective study was initiated to compare the rapid test with an antigen capture enzyme immunoassay (EIA) and a nested reverse transcriptase PCR (RT-PCR) protocol for detection of RSV serotypes A and B. Only respiratory samples from children exhibiting the prolonged presence of RSV (≥5 days) as determined by the rapid test were considered. A total of 134 specimens from 24 children was investigated by antigen capture EIA and nested RT-PCR. Using RT-PCR as the reference method, we determined the RSV rapid test to have a specificity of 63% and a sensitivity of 66% and the antigen capture EIA to have a specificity of 96% and a sensitivity of 69% for acute-phase samples and the homologous virus serotype A. In 7 (29%) of 24 patients, the positive results of the RSV rapid test could not be confirmed by either nested RT-PCR or antigen capture EIA. In these seven patients a variety of other respiratory viruses were detected. For general screening the RSV rapid test was found to be a reasonable tool to get quick results. However, its lack of specificity in some patients requires confirmation by additional tests to rule out false-positive results and/or detection of other respiratory viruses. PMID:11526141

  11. PAK1 and CtBP1 Regulate the Coupling of Neuronal Activity to Muscle Chromatin and Gene Expression

    PubMed Central

    Thomas, Jean-Luc; Ravel-Chapuis, Aymeric; Valente, Carmen; Corda, Daniela; Méjat, Alexandre

    2015-01-01

    Acetylcholine receptor (AChR) expression in innervated muscle is limited to the synaptic region. Neuron-induced electrical activity participates in this compartmentalization by promoting the repression of AChR expression in the extrasynaptic regions. Here, we show that the corepressor CtBP1 (C-terminal binding protein 1) is present on the myogenin promoter together with repressive histone marks. shRNA-mediated downregulation of CtBP1 expression is sufficient to derepress myogenin and AChR expression in innervated muscle. Upon denervation, CtBP1 is displaced from the myogenin promoter and relocates to the cytoplasm, while repressive histone marks are replaced by activating ones concomitantly to the activation of myogenin expression. We also observed that upon denervation the p21-activated kinase 1 (PAK1) expression is upregulated, suggesting that phosphorylation by PAK1 may be involved in the relocation of CtBP1. Indeed, preventing CtBP1 Ser158 phosphorylation induces CtBP1 accumulation in the nuclei and abrogates the activation of myogenin and AChR expression. Altogether, these findings reveal a molecular mechanism to account for the coordinated control of chromatin modifications and muscle gene expression by presynaptic neurons via a PAK1/CtBP1 pathway. PMID:26416879

  12. Yarn Quality Prediction Based on Improved BP Neural Network

    NASA Astrophysics Data System (ADS)

    Yang, Jian-Guo; Xiong, Jing-Wei; Xun, Lan

    Aiming at the key quality indexes xbt in spinning processing is caused by many complex and interactions factors. A xbt prediction model is put forward based on the PSO-BP neural network, which adjusts weights of BP neural network using particle swarm optimization (PSO) rather than the traditional gradient descent method, is used to improve the convergence speed of neural network and the ability of getting the global optimal solution. As the object of a large number of field detection data in a spinning workshop, the results show that, compared with the traditional BP algorithm and GA-BP algorithm, the PSO-BP neural network can obvious improve yarn quality prediction model precision and stability.

  13. Calculation of the Cost of an Adequate Education in Kentucky: A Professional Judgment Approach

    ERIC Educational Resources Information Center

    Verstegen, Deborah A.

    2004-01-01

    What is an adequate education and how much does it cost? In 1989, Kentucky's State Supreme Court found the entire system of education unconstitutional--"all of its parts and parcels". The Court called for all children to have access to an adequate education, one that is uniform and has as its goal the development of seven capacities, including:…

  14. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  15. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Exemptions for pesticides adequately... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION PROCEDURES Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The...

  16. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical devices; adequate directions for use. 801.5 Section 801.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate...

  17. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical devices; adequate directions for use. 801.5 Section 801.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate...

  18. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical devices; adequate directions for use. 801.5 Section 801.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate...

  19. 21 CFR 801.5 - Medical devices; adequate directions for use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical devices; adequate directions for use. 801.5 Section 801.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES LABELING General Labeling Provisions § 801.5 Medical devices; adequate...

  20. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... regulated by another Federal agency. 152.20 Section 152.20 Protection of Environment ENVIRONMENTAL... Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The pesticides... has determined, in accordance with FIFRA sec. 25(b)(1), that they are adequately regulated by...

  1. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... regulated by another Federal agency. 152.20 Section 152.20 Protection of Environment ENVIRONMENTAL... Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The pesticides... has determined, in accordance with FIFRA sec. 25(b)(1), that they are adequately regulated by...

  2. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... regulated by another Federal agency. 152.20 Section 152.20 Protection of Environment ENVIRONMENTAL... Exemptions § 152.20 Exemptions for pesticides adequately regulated by another Federal agency. The pesticides... has determined, in accordance with FIFRA sec. 25(b)(1), that they are adequately regulated by...

  3. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Adequate financial records, statistical data, and....568 Adequate financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination...

  4. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Adequate financial records, statistical data, and....568 Adequate financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination...

  5. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Adequate financial records, statistical data, and....568 Adequate financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination...

  6. The structural basis of modified nucleosome recognition by 53BP1.

    PubMed

    Wilson, Marcus D; Benlekbir, Samir; Fradet-Turcotte, Amélie; Sherker, Alana; Julien, Jean-Philippe; McEwan, Andrea; Noordermeer, Sylvie M; Sicheri, Frank; Rubinstein, John L; Durocher, Daniel

    2016-08-01

    DNA double-strand breaks (DSBs) elicit a histone modification cascade that controls DNA repair. This pathway involves the sequential ubiquitination of histones H1 and H2A by the E3 ubiquitin ligases RNF8 and RNF168, respectively. RNF168 ubiquitinates H2A on lysine 13 and lysine 15 (refs 7, 8) (yielding H2AK13ub and H2AK15ub, respectively), an event that triggers the recruitment of 53BP1 (also known as TP53BP1) to chromatin flanking DSBs. 53BP1 binds specifically to H2AK15ub-containing nucleosomes through a peptide segment termed the ubiquitination-dependent recruitment motif (UDR), which requires the simultaneous engagement of histone H4 lysine 20 dimethylation (H4K20me2) by its tandem Tudor domain. How 53BP1 interacts with these two histone marks in the nucleosomal context, how it recognizes ubiquitin, and how it discriminates between H2AK13ub and H2AK15ub is unknown. Here we present the electron cryomicroscopy (cryo-EM) structure of a dimerized human 53BP1 fragment bound to a H4K20me2-containing and H2AK15ub-containing nucleosome core particle (NCP-ubme) at 4.5 Å resolution. The structure reveals that H4K20me2 and H2AK15ub recognition involves intimate contacts with multiple nucleosomal elements including the acidic patch. Ubiquitin recognition by 53BP1 is unusual and involves the sandwiching of the UDR segment between ubiquitin and the NCP surface. The selectivity for H2AK15ub is imparted by two arginine fingers in the H2A amino-terminal tail, which straddle the nucleosomal DNA and serve to position ubiquitin over the NCP-bound UDR segment. The structure of the complex between NCP-ubme and 53BP1 reveals the basis of 53BP1 recruitment to DSB sites and illuminates how combinations of histone marks and nucleosomal elements cooperate to produce highly specific chromatin responses, such as those elicited following chromosome breaks.

  7. BpTRUth: do automated blood pressure monitors outperform mercury?

    PubMed

    Edwards, Cedric; Hiremath, Swapnil; Gupta, Ankur; McCormick, Brendan B; Ruzicka, Marcel

    2013-01-01

    Manual measurement of blood pressure (BP) in the office (MOBP) is inferior in accuracy when compared with ambulatory BP measurements (ABPM) since it misses white coat and masked effects on BP. BpTRU, an automated office BP device (AOBP), has been reported to reduce white coat effect. We performed a retrospective review of the diagnostic accuracy of MOBP (taken by a trained nurse in clinical hypertension) and AOBP using the Bland-Altman method in hypertensive patients referred to a Renal Hypertension Clinic. In 329 hypertensive patients, the 95% limits of agreement between systolic AOBP and ABPM were -31 mm Hg to 33 mm Hg and for MOBP and ABPM were -27.8 mm Hg to 37.4 mm Hg. The bias between systolic MOBP and systolic ABPM was 4.9 mm Hg (95% confidence interval, 3.0-6.6 mm Hg) whereas the bias between the systolic AOBP and the systolic ABPM was -3.2 (95% confidence interval, -1.3 to -5.0). AOBP did not improve treatment relevant classification errors compared with MOBP (28% vs. 23%; P = .052). Our data support findings by others showing that AOBP improves, but does not eliminate, white coat effect. The increased detection of white coat effect appears related to systematic downward bias by BpTRU. As a result, detection of masked effect is undermined by BpTRU. PMID:23969286

  8. 45 CFR 1159.15 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... adequate technical, physical, and security safeguards to prevent unauthorized disclosure or destruction of... of maintaining adequate technical, physical, and security safeguards to prevent...

  9. Determining which automatic digital blood pressure device performs adequately: a systematic review

    PubMed Central

    Wan, Y; Heneghan, C; Stevens, R; McManus, R J; Ward, A; Perera, R; Thompson, M; Tarassenko, L; Mant, D

    2010-01-01

    The aim of this study is to systematically examine the proportion of accurate readings attained by automatic digital blood pressure (BP) devices in published validation studies. We included studies of automatic digital BP devices using recognized protocols. We summarized the data as mean and s.d. of differences between measured and observed BP, and proportion of measurements within 5 mm Hg. We included 79 articles (10 783 participants) reporting 113 studies from 22 different countries. Overall, 25/31 (81%), 37/41 (90%) and 34/35 (97%) devices passed the relevant protocols [BHS, AAMI and ESH international protocol (ESH-IP), respectively]. For devices that passed the BHS protocol, the proportion of measured values within 5 mm Hg of the observed value ranged from 60 to 86% (AAMI protocol 47–94% and ESH-IP 54–89%). The results for the same device varied significantly when a different protocol was used (Omron HEM-907 80% of readings were within 5 mm Hg using the AAMI protocol compared with 62% with the ESH-IP). Even devices with a mean difference of zero show high variation: a device with 74% of BP measurements within 5 mm Hg would require six further BP measurements to reduce variation to 95% of readings within 5 mm Hg. Current protocols for validating BP monitors give no guarantee of accuracy in clinical practice. Devices may pass even the most rigorous protocol with as few as 60% of readings within 5 mm Hg of the observed value. Multiple readings are essential to provide clinicians and patients with accurate information on which to base diagnostic and treatment decisions. PMID:20376077

  10. Ran-dependent docking of importin-beta to RanBP2/Nup358 filaments is essential for protein import and cell viability.

    PubMed

    Hamada, Masakazu; Haeger, Anna; Jeganathan, Karthik B; van Ree, Janine H; Malureanu, Liviu; Wälde, Sarah; Joseph, Jomon; Kehlenbach, Ralph H; van Deursen, Jan M

    2011-08-22

    RanBP2/Nup358, the major component of the cytoplasmic filaments of the nuclear pore complex (NPC), is essential for mouse embryogenesis and is implicated in both macromolecular transport and mitosis, but its specific molecular functions are unknown. Using RanBP2 conditional knockout mouse embryonic fibroblasts and a series of mutant constructs, we show that transport, rather than mitotic, functions of RanBP2 are required for cell viability. Cre-mediated RanBP2 inactivation caused cell death with defects in M9- and classical nuclear localization signal (cNLS)-mediated protein import, nuclear export signal-mediated protein export, and messenger ribonucleic acid export but no apparent mitotic failure. A short N-terminal RanBP2 fragment harboring the NPC-binding domain, three phenylalanine-glycine motifs, and one Ran-binding domain (RBD) corrected all transport defects and restored viability. Mutation of the RBD within this fragment caused lethality and perturbed binding to Ran guanosine triphosphate (GTP)-importin-β, accumulation of importin-β at nuclear pores, and cNLS-mediated protein import. These data suggest that a critical function of RanBP2 is to capture recycling RanGTP-importin-β complexes at cytoplasmic fibrils to allow for adequate cNLS-mediated cargo import. PMID:21859863

  11. Evaluation of the Specificity of BP3385 for Bordetella pertussis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BP3385 has been proposed as a diagnostic PCR target for discriminating between Bordetella pertussis and other Bordetella species that also infect humans. Our results demonstrate this gene is also present in some strains of Bordetella hinzii and Bordetella bronchiseptica....

  12. TopBP1 Interacts with BLM to Maintain Genome Stability but Is Dispensable for Preventing BLM Degradation

    PubMed Central

    Blackford, Andrew N.; Nieminuszczy, Jadwiga; Schwab, Rebekka A.; Galanty, Yaron; Jackson, Stephen P.; Niedzwiedz, Wojciech

    2015-01-01

    Summary The Bloom syndrome helicase BLM and topoisomerase-IIβ-binding protein 1 (TopBP1) are key regulators of genome stability. It was recently proposed that BLM phosphorylation on Ser338 mediates its interaction with TopBP1, to protect BLM from ubiquitylation and degradation (Wang et al., 2013). Here, we show that the BLM-TopBP1 interaction does not involve Ser338 but instead requires BLM phosphorylation on Ser304. Furthermore, we establish that disrupting this interaction does not markedly affect BLM stability. However, BLM-TopBP1 binding is important for maintaining genome integrity, because in its absence cells display increased sister chromatid exchanges, replication origin firing and chromosomal aberrations. Therefore, the BLM-TopBP1 interaction maintains genome stability not by controlling BLM protein levels, but via another as-yet undetermined mechanism. Finally, we identify critical residues that mediate interactions between TopBP1 and MDC1, and between BLM and TOP3A/RMI1/RMI2. Taken together, our findings provide molecular insights into a key tumor suppressor and genome stability network. PMID:25794620

  13. Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

    PubMed

    Laaribi, A B; Zidi, I; Hannachi, N; Ben Yahia, H; Chaouch, H; Bortolotti, D; Zidi, N; Letaief, A; Yacoub, S; Boudabous, A; Rizzo, R; Boukadida, J

    2015-10-01

    Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation.

  14. Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

    PubMed

    Laaribi, A B; Zidi, I; Hannachi, N; Ben Yahia, H; Chaouch, H; Bortolotti, D; Zidi, N; Letaief, A; Yacoub, S; Boudabous, A; Rizzo, R; Boukadida, J

    2015-10-01

    Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation. PMID:25619305

  15. Structural basis for the sequence-specific RNA-recognition mechanism of human CUG-BP1 RRM3

    PubMed Central

    Tsuda, Kengo; Kuwasako, Kanako; Takahashi, Mari; Someya, Tatsuhiko; Inoue, Makoto; Terada, Takaho; Kobayashi, Naohiro; Shirouzu, Mikako; Kigawa, Takanori; Tanaka, Akiko; Sugano, Sumio; Güntert, Peter; Muto, Yutaka; Yokoyama, Shigeyuki

    2009-01-01

    The CUG-binding protein 1 (CUG-BP1) is a member of the CUG-BP1 and ETR-like factors (CELF) family or the Bruno-like family and is involved in the control of splicing, translation and mRNA degradation. Several target RNA sequences of CUG-BP1 have been predicted, such as the CUG triplet repeat, the GU-rich sequences and the AU-rich element of nuclear pre-mRNAs and/or cytoplasmic mRNA. CUG-BP1 has three RNA-recognition motifs (RRMs), among which the third RRM (RRM3) can bind to the target RNAs on its own. In this study, we solved the solution structure of the CUG-BP1 RRM3 by hetero-nuclear NMR spectroscopy. The CUG-BP1 RRM3 exhibited a noncanonical RRM fold, with the four-stranded β-sheet surface tightly associated with the N-terminal extension. Furthermore, we determined the solution structure of the CUG-BP1 RRM3 in the complex with (UG)3 RNA, and discovered that the UGU trinucleotide is specifically recognized through extensive stacking interactions and hydrogen bonds within the pocket formed by the β-sheet surface and the N-terminal extension. This study revealed the unique mechanism that enables the CUG-BP1 RRM3 to discriminate the short RNA segment from other sequences, thus providing the molecular basis for the comprehension of the role of the RRM3s in the CELF/Bruno-like family. PMID:19553194

  16. Inhibition of 4E-BP1 Sensitizes U87 Glioblastoma Xenograft Tumors to Irradiation by Decreasing Hypoxia Tolerance

    SciTech Connect

    Dubois, Ludwig; Magagnin, Michael G.; Cleven, Arjen H.G.; Weppler, Sherry A.; Grenacher, Beat; Landuyt, Willy; Lieuwes, Natasja; Lambin, Philippe; Gorr, Thomas A.; Koritzinsky, Marianne

    2009-03-15

    Purpose: Eukaryotic initiation factor 4E (eIF4E) is an essential rate-limiting factor for cap-dependent translation in eukaryotic cells. Elevated eIF4E activity is common in many human tumors and is associated with disease progression. The growth-promoting effects of eIF4E are in turn negatively regulated by 4E-BP1. However, although 4E-BP1 harbors anti-growth activity, its expression is paradoxically elevated in some tumors. The aim of this study was to investigate the functional role of 4E-BP1 in the context of solid tumors. Methods and Materials: In vitro and in vivo growth properties, hypoxia tolerance, and response to radiation were assessed for HeLa and U87 cells, after stable expression of shRNA specific for 4E-BP1. Results: We found that loss of 4E-BP1 expression did not significantly alter in vitro growth but did accelerate the growth of U87 tumor xenografts, consistent with the growth-promoting function of deregulated eIF4E. However, cells lacking 4E-BP1 were significantly more sensitive to hypoxia-induced cell death in vitro. Furthermore, 4E-BP1 knockdown cells produced tumors more sensitive to radiation because of a reduction in the viable fraction of radioresistant hypoxic cells. Decreased hypoxia tolerance in the 4E-BP1 knockdown tumors was evident by increased cleaved caspase-3 levels and was associated with a reduction in adenosine triphosphate (ATP). Conclusions: Our results suggest that although tumors often demonstrate increases in cap-dependent translation, regulation of this activity is required to facilitate energy conservation, hypoxia tolerance, and tumor radioresistance. Furthermore, we suggest that targeting translational control may be an effective way to target hypoxic cells and radioresistance in metabolically hyperactive tumors.

  17. Close-spaced crystal growth and characterization of BP crystals

    NASA Astrophysics Data System (ADS)

    Schmitt, J. O.; Edgar, L. J. H.; Liu, L.; Nagarajan, R.; Szyszko, T.; Podsiadlo, S.; Wojciech, G.

    2005-02-01

    The present study was undertaken to determine if boron phosphide (BP) crystals could be produced by a simple technique, close-spaced vapor transport (CVST). This technique has proven very successful in achieving very high growth rates for a wide variety of materials including ZnSe, AlN, and SiC. Both silicon (100) and sapphire substrates were used for the CSVT growth. The resulting films were characterized by Raman spectroscopy. Sublimation of BP powder from 1050 to 1450 °C in an argon atmosphere produced a range of deep orange colour, single and polycrystalline BP crystals. The crystal size increased and the crystal density decreased with increasing temperature. Well-faceted crystals were produced at an intermediate temperature of 1200 °C. At temperatures higher then 1450 °C no BP crystals were grown. Only a fibrous mass of fine whiskers, loosely attached to the substrate were produced. The peak position of the Raman LO mode of the BP crystals was shifted to higher wavenumbers than the BP powder source, suggesting that the crystals were compressively strained.

  18. Black Phosphorus (BP) Nanodots for Potential Biomedical Applications.

    PubMed

    Lee, Hyun Uk; Park, So Young; Lee, Soon Chang; Choi, Saehae; Seo, Soonjoo; Kim, Hyeran; Won, Jonghan; Choi, Kyuseok; Kang, Kyoung Suk; Park, Hyun Gyu; Kim, Hee-Sik; An, Ha Rim; Jeong, Kwang-Hun; Lee, Young-Chul; Lee, Jouhahn

    2016-01-13

    Recently, the appeal of 2D black phosphorus (BP) has been rising due to its unique optical and electronic properties with a tunable band gap (≈0.3-1.5 eV). While numerous research efforts have recently been devoted to nano- and optoelectronic applications of BP, no attention has been paid to promising medical applications. In this article, the preparation of BP-nanodots of a few nm to <20 nm with an average diameter of ≈10 nm and height of ≈8.7 nm is reported by a modified ultrasonication-assisted solution method. Stable formation of nontoxic phosphates and phosphonates from BP crystals with exposure in water or air is observed. As for the BP-nanodot crystals' stability (ionization and persistence of fluorescent intensity) in aqueous solution, after 10 d, ≈80% at 1.5 mg mL(-1) are degraded (i.e., ionized) in phosphate buffered saline. They showed no or little cytotoxic cell-viability effects in vitro involving blue- and green-fluorescence cell imaging. Thus, BP-nanodots can be considered a promising agent for drug delivery or cellular tracking systems.

  19. The Need for Domestic Violence Laws with Adequate Legal and Social Support Services.

    ERIC Educational Resources Information Center

    Hemmons, Willa M.

    1981-01-01

    Describes the need for comprehensive domestic violence programs that include medical, legal, economic, psychological, and child care services. Although most states have family violence legislation, more work is needed to adequately implement these programs. (Author/JAC)

  20. Thermal and chemical denaturation of the BRCT functional module of human 53BP1.

    PubMed

    Thanassoulas, Angelos; Nomikos, Michail; Theodoridou, Maria; Stavros, Philemon; Mastellos, Dimitris; Nounesis, George

    2011-10-01

    BRCTs are protein-docking modules involved in eukaryotic DNA repair. They are characterized by low sequence homology with generally well-conserved structure organization. In a considerable number of proteins, a pair of BRCT structural repeats occurs, connected with inter-BRCT linkers, variable in length, sequence and structure. Linkers may separate and control the relative position of BRCT domains as well as protect and stabilize the hydrophobic inter-BRCT interface region. Their vital role in protein function has been demonstrated by recent findings associating missense mutations in the inter-repeat linker region of the BRCT domain of BRCA1 (BRCA1-BRCT) to hereditary breast/ovarian cancer. The interaction of 53BP1 with the core domain of the p53 tumor suppressor involves the C-terminal BRCT repeat as well as the inert-BRCT linker of the tandem BRCT domain of 53BP1 (53BP1-BRCT). High-accuracy differential scanning calorimetry (DSC) and circular dichroism (CD) have been employed to characterize the heat-induced unfolding of 53BP1-BRCT domain. The calorimetric results provide evidence for unfolding to an intermediate, only partly unfolded state, which, based on the CD results, retains the secondary structural characteristics of the native protein. A direct comparison with the corresponding thermal processes for BRAC1-BRCT and BARD1-BRCT provides evidence that the observed behavior is analogous to BRCA1-BRCT even though the two domains differ substantially in the linker structure. Moreover, chemical denaturation experiments of the untagged 53BP1-BRCT and comparison with BRCA1 and BARD1 BRCTs show that no clear association can be drawn between the structural organization of the inter-BRCT linkers and the overall stability of the BRCT domains.

  1. Rasputin, more promiscuous than ever: a review of G3BP.

    PubMed

    Irvine, Katharine; Stirling, Renee; Hume, David; Kennedy, Derek

    2004-12-01

    In this review, we highlight what G3BP's domain structure initially suggested; that G3BPs are "scaffolding" proteins linking signal transduction to RNA metabolism. Whilst it is most attractive to hypothesise about G3BP's role in signalling to mRNA metabolism, it is not known whether all G3BP functions impinge on their RNA-binding activities, so any theories are naturally subject to this qualification. It is hypothesised that, in coordination with an array of other proteins, G3BP, in a phosphorylation-dependent manner, is involved in the post-transcriptional regulation of a subset of mRNAs, at least some of which are in common with those regulated by Hu proteins. These transcripts, partially controlled at the post-transcriptional level by G3BPs, code for proteins important in transcription (e.g. c-Myc) and cytoskeletal arrangement (e.g. Tau), amongst other as yet undetermined pathways. The subtle differences between G3BP family members could dictate binding to a variety of signalling proteins, so each of the G3BPs may participate in different, though possibly related mRNPs, which are assembled in response to different stimuli. The combinatorial nature of the mRNP complex offers a powerful means of regulating gene expression, beyond that provided by a simple mRNA sequence. The ways in which mRNP flexibility and specificity may be harnessed to coordinate gene expression of functionally or structurally related mRNAs are not yet fully appreciated. Characterising mRNP composition and the function/s of mRNP components, such as the G3BPs, will aid in the understanding of how post-transcriptional mechanisms contribute to the global regulation of gene expression.

  2. T-cell involvement in sex differences in blood pressure control.

    PubMed

    Crislip, G Ryan; Sullivan, Jennifer C

    2016-05-01

    Hypertension affects one-third of adults in the Western world and is the most common independent risk factor for cardiovascular disease, and the leading cause of premature death globally. Despite available therapeutic options, approximately half of the hypertensive population taking medication does not achieve adequate blood pressure (BP) control leaving them at increased risk of chronic kidney disease, renal failure, stroke, congestive heart failure, myocardial infarction, aneurysm and peripheral artery disease. New therapeutic options need to be identified for the treatment of hypertension in order to increase the percentage of individuals with controlled BP. There is a growing basic science literature regarding the role of T-cells in the pathogenesis of hypertension and BP control; however, the majority of this literature has been performed exclusively in males despite the fact that both men and women develop hypertension. This is especially problematic since hypertension is well recognized as having distinct sex differences in the prevalence, absolute BP values and molecular mechanisms contributing to the pathophysiology of the disease. The purpose of this article is to review the available literature regarding sex differences in T-cells in hypertension followed by highlighting the potential pathways that may result in sex-specific effects on T-cell activation and differentiation. PMID:27128802

  3. BP and Vascular Function Following Space Flight

    NASA Technical Reports Server (NTRS)

    Hatton, Daniel C.; Yue, Qi; Chapman, Justin; Xue, Hong; Dierickx, Jacqueline; Roullet, Chantal; Roullet, Jean-Baptiste; Phanouvong, Thongchanh; Watanabe, Mitsuaki; Otsuka, Keiichi; McCarron, David A.

    1997-01-01

    Blood pressure and mesenteric resistance artery function were assessed in 9-week-old spontaneously hypertensive rats following an 18 day shuttle flight on STS-80. Blood pressure was measured twice, first in conscious animals using a tail-cuff method and then while the animals were anesthetized with 2% halothane in O2. Isolated mesenteric resistance artery responses to cumulative additions of norepinephrine, acetylcholine, sodium nitroprusside, and calcium were measured within 17 hours of landing using wire myography. Blood pressure was slightly reduced in conscious animals following flight (p=0.056) but was significantly elevated (p less than.001) above vivarium control group values in anesthetized animals. Maximal contraction of mesenteric arteries to norepinephrine was attenuated in the flight animals (p less than.001)aswasrelaxationtoacetylcholine(p less than .001)andcalcium(p less than .05). There was no difference between flight and control animals in the vessel response to sodium nitroprusside (p greater than .05). The results suggest that there may have been an increase in synthesis and release of nitric oxide in the flight animals.

  4. Patient acceptance of adequately filled breast implants using the tilt test.

    PubMed

    Tebbetts, J B

    2000-07-01

    Adequate fill of any breast implant, regardless of shell characteristics, shape, or filler material, is important to prevent implant shell wrinkling, folding, or collapse that could potentially decrease the life of the implant. Implant shell life is a major factor that affects reoperation rates. The greater the necessity of reoperations, regardless of implant type, the greater the rate of local complications, necessitating additional surgery with additional risks and costs to patients. Palpable shell folding, visible wrinkling or rippling, palpable shifts of filler material, sloshing, and compromised aesthetic results can result from an under-filled implant. Any of these complications can necessitate reoperations with increased risks and costs to patients. This is a study of 609 consecutive patients from January of 1993 to December of 1998 who were given detailed preoperative informed consent and a choice of implant shape and type and who chose the increased firmness associated with an implant that is adequately filled to pass the tilt test. This study addresses two questions: (1) Will patients accept the increased firmness of an implant that is filled to pass the tilt test? and (2) Is adequate fill by the tilt test useful clinically to help reduce the incidence of postoperative rippling, wrinkling, and spontaneous deflation in saline implants? Patients were followed by postoperative examinations and questionnaires. No patient requested implant replacement to a softer implant postoperatively, and no reoperations were performed for visible rippling or wrinkling. The spontaneous deflation rate over this 6-year period was 9 of 1218 implants, or 0.739 percent. If patients will accept more firmness with an adequately filled implant, regardless of the filler material, surgeons might worry less about recommending an adequately filled implant to patients, and manufacturers might feel more comfortable producing adequately filled implants and redefining fill volumes for

  5. Ensuring Adequate Health and Safety Information for Decision Makers during Large-Scale Chemical Releases

    NASA Astrophysics Data System (ADS)

    Petropoulos, Z.; Clavin, C.; Zuckerman, B.

    2015-12-01

    The 2014 4-Methylcyclohexanemethanol (MCHM) spill in the Elk River of West Virginia highlighted existing gaps in emergency planning for, and response to, large-scale chemical releases in the United States. The Emergency Planning and Community Right-to-Know Act requires that facilities with hazardous substances provide Material Safety Data Sheets (MSDSs), which contain health and safety information on the hazardous substances. The MSDS produced by Eastman Chemical Company, the manufacturer of MCHM, listed "no data available" for various human toxicity subcategories, such as reproductive toxicity and carcinogenicity. As a result of incomplete toxicity data, the public and media received conflicting messages on the safety of the contaminated water from government officials, industry, and the public health community. Two days after the governor lifted the ban on water use, the health department partially retracted the ban by warning pregnant women to continue avoiding the contaminated water, which the Centers for Disease Control and Prevention deemed safe three weeks later. The response in West Virginia represents a failure in risk communication and calls to question if government officials have sufficient information to support evidence-based decisions during future incidents. Research capabilities, like the National Science Foundation RAPID funding, can provide a solution to some of the data gaps, such as information on environmental fate in the case of the MCHM spill. In order to inform policy discussions on this issue, a methodology for assessing the outcomes of RAPID and similar National Institutes of Health grants in the context of emergency response is employed to examine the efficacy of research-based capabilities in enhancing public health decision making capacity. The results of this assessment highlight potential roles rapid scientific research can fill in ensuring adequate health and safety data is readily available for decision makers during large

  6. Maintaining Adequate Carbon Dioxide Washout for an Advanced Extravehicular Mobility Unit

    NASA Technical Reports Server (NTRS)

    Chullen, Cinda; Navarro, Moses; Conger, Bruce; Korona, Adam; McMillin, Summer; Norcross, Jason; Swickrath, Mike

    2013-01-01

    Over the past several years, NASA has realized tremendous progress in technology development that is aimed at the production of an Advanced Extravehicular Mobility Unit (AEMU). Of the many functions provided by the spacesuit and portable life support subsystem within the AEMU, delivering breathing gas to the astronaut along with removing the carbon dioxide (CO2) remains one of the most important environmental functions that the AEMU can control. Carbon dioxide washout is the capability of the ventilation flow in the spacesuit helmet to provide low concentrations of CO2 to the crew member to meet breathing requirements. CO2 washout performance is a critical parameter needed to ensure proper and sufficient designs in a spacesuit and in vehicle applications such as sleep stations and hygiene compartments. Human testing to fully evaluate and validate CO2 washout performance is necessary but also expensive due to the levied safety requirements. Moreover, correlation of math models becomes challenging because of human variability and movement. To supplement human CO2 washout testing, a breathing capability will be integrated into a suited manikin test apparatus to provide a safe, lower cost, stable, easily modeled alternative to human testing. Additionally, this configuration provides NASA Johnson Space Center (JSC) the capability to evaluate CO2 washout under off-nominal conditions that would otherwise be unsafe for human testing or difficult due to fatigue of a test subject. Testing has been under way in-house at JSC and analysis has been initiated to evaluate whether the technology provides sufficient performance in ensuring that the CO2 is removed sufficiently and the ventilation flow is adequate for maintaining CO2 washout in the AEMU spacesuit helmet of the crew member during an extravehicular activity. This paper will review recent CO2 washout testing and analysis activities, testing planned in-house with a spacesuit simulator, and the associated analytical work

  7. Emotional Experiences of Obese Women with Adequate Gestational Weight Variation: A Qualitative Study

    PubMed Central

    Faria-Schützer, Débora Bicudo; Surita, Fernanda Garanhani de Castro; Alves, Vera Lucia Pereira; Vieira, Carla Maria; Turato, Egberto Ribeiro

    2015-01-01

    Background As a result of the growth of the obese population, the number of obese women of fertile age has increased in the last few years. Obesity in pregnancy is related to greater levels of anxiety, depression and physical harm. However, pregnancy is an opportune moment for the intervention of health care professionals to address obesity. The objective of this study was to describe how obese pregnant women emotionally experience success in adequate weight control. Methods and Findings Using a qualitative design that seeks to understand content in the field of health, the sample of subjects was deliberated, with thirteen obese pregnant women selected to participate in an individual interview. Data was analysed by inductive content analysis and includes complete transcription of the interviews, re-readings using suspended attention, categorization in discussion topics and the qualitative and inductive analysis of the content. The analysis revealed four categories, three of which show the trajectory of body care that obese women experience during pregnancy: 1) The obese pregnant woman starts to think about her body;2) The challenge of the diet for the obese pregnant woman; 3) The relation of the obese pregnant woman with the team of antenatal professionals. The fourth category reveals the origin of the motivation for the change: 4) The potentializing factors for change: the motivation of the obese woman while pregnant. Conclusions During pregnancy, obese women are more in touch with themselves and with their emotional conflicts. Through the transformations of their bodies, women can start a more refined self-care process and experience of the body-mind unit. The fear for their own and their baby's life, due to the risks posed by obesity, appears to be a great potentializing factor for change. The relationship with the professionals of the health care team plays an important role in the motivational support of the obese pregnant woman. PMID:26529600

  8. Polyphenolic drug composition based on benzenepolycarboxylic acids (BP-C3) increases life span and inhibits spontaneous tumorigenesis in female SHR mice

    PubMed Central

    Anisimov, Vladimir N.; Popovich, Irina G.; Zabezhinski, Mark A.; Yurova, Maria N.; Tyndyk, Margarita L.; Anikin, Ivan V.; Egormin, Peter A.; Baldueva, Irina A.; Fedoros, Elena I.; Pigarev, Sergey E.; Panchenko, Andrey V.

    2016-01-01

    Effects of long-term application of novel polyphenolic composition BP-C3, containing polyphenolic benzenepolycarboxylic acids, vitamins and minerals on some biomarkers of aging, life span and spontaneous tumorigenesis has been studied in female SHR mice. Administration of BP-C3 with drinking water (0.005%) did not exert any toxic effect (did not have effect on general condition of animals, weight dynamics and consumption of food), postponed age-related switch-off of estrous function, caused slight reduction of body temperature. An increased survival was observed in mice treated with BP-C3 (p=0.00164, log rank test). BP-C3 increased mean lifespan – by 8.4%, lifespan of the last 10% of animals – by 12.4%, and life span of tumor-free mice – by 11.6%. A tendency in ability of BP-C3 to inhibit development of spontaneous tumors in mice was detected, though it did not reach the level of statistical significance (p=0.166, log rank test). The number of malignant mammary tumors was 1.5 times less and total number of tumors of various localizations was 1.6 times less in BP-C3 treated animals. Multiple tumors were registered in 8% of mice in the control group and no cases – in BP-C3 treated group. Thus, BP-C3 demonstrated some anti-carcinogenic and a pronounced geroprotective activity. PMID:27574962

  9. The remarkably unremarkable global abundance variations of the magnetic Bp star HD 133652

    NASA Astrophysics Data System (ADS)

    Bailey, J. D.; Landstreet, J. D.

    2015-08-01

    Context. In recent years, significant effort has been made to understand how the magnetic field strengths and atmospheric chemical abundances of Ap/Bp stars evolve during their main sequence lifetime by identifying a large number of Ap/Bp stars with accurately known ages. As a next step, these stars should be studied individually and in detail to offer further insight into the physics of how such main sequence stars evolve. Aims: We have obtained high resolution spectra using the ESPaDOnS spectropolarimeter and FEROS spectrograph of the chemically peculiar, magnetic Bp star HD 133652. Using these data, we present a simple magnetic field model and abundance determinations of He, O, Mg, Si, Ti, Cr, Fe, Pr, and Nd. Methods: Abundance analysis was performed using zeeman.f, a spectral synthesis program that includes the effects of magnetic fields on line formation. The magnetic field structure is approximated as a simple, co-linear multipole expansion that reproduces the observed variations of the line-of-sight magnetic field with phase. The abundance distribution of each element was modelled using a uniform abundance in each of the two magnetic hemispheres. Results: Using the new magnetic field measurements, we were able to refine the rotation period of HD 133652 to P = 2.30405 ± 0.00002 d. The abundance analysis reveals that the elements modelled (except He, O and Mg) are overabundant compared to the Sun; however most elements studied do not show substantial differences in the large-scale mean abundances between the two magnetic hemispheres. The individual line profiles are very complex and clearly indicate the presence of significant small-scale abundance variations on the stellar surface. Conclusions: These data are adequate to perform a useful investigation of the magnetic field structure and abundance distribution over the stellar surface. HD 133652 is now one of a growing list of hotter Bp stars of known age for which this type of analysis has been performed

  10. Marine04 Marine radiocarbon age calibration, 26 ? 0 ka BP

    SciTech Connect

    Hughen, K; Baille, M; Bard, E; Beck, J; Bertrand, C; Blackwell, P; Buck, C; Burr, G; Cutler, K; Damon, P; Edwards, R; Fairbanks, R; Friedrich, M; Guilderson, T; Kromer, B; McCormac, F; Manning, S; Bronk-Ramsey, C; Reimer, P; Reimer, R; Remmele, S; Southon, J; Stuiver, M; Talamo, S; Taylor, F; der Plicht, J v; Weyhenmeyer, C

    2004-11-01

    New radiocarbon calibration curves, IntCal04 and Marine04, have been constructed and internationally ratified to replace the terrestrial and marine components of IntCal98. The new calibration datasets extend an additional 2000 years, from 0-26 ka cal BP (Before Present, 0 cal BP = AD 1950), and provide much higher resolution, greater precision and more detailed structure than IntCal98. For the Marine04 curve, dendrochronologically dated tree-ring samples, converted with a box-diffusion model to marine mixed-layer ages, cover the period from 0-10.5 ka cal BP. Beyond 10.5 ka cal BP, high-resolution marine data become available from foraminifera in varved sediments and U/Th-dated corals. The marine records are corrected with site-specific {sup 14}C reservoir age information to provide a single global marine mixed-layer calibration from 10.5-26.0 ka cal BP. A substantial enhancement relative to IntCal98 is the introduction of a random walk model, which takes into account the uncertainty in both the calendar age and the radiocarbon age to calculate the underlying calibration curve. The marine datasets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed here. The tree-ring datasets, sources of uncertainty, and regional offsets are presented in detail in a companion paper by Reimer et al.

  11. Preliminary Geological Findings on the BP-1 Simulant

    NASA Technical Reports Server (NTRS)

    Rickman, D. L.

    2010-01-01

    The following is a summation of information and discussion between Doug Stoeser of the USGS and Doug Rickman of NASA in February and March, 2010 pertaining to the BP-1 simulant. The analytical results and the bulk of the text are from communications from Dr. Stoeser. The BP-1 simulant is made from Black Point Basalt Flow, San Francisco Volcanic Field, northern Arizona. There is an aggregate (road metal) quarry on the northern margin of the flow towards the west end that was used as a Desert Research and Technology Studies (Desert RATS) analog test site. Silty material from this site was also used in laboratory tests and found to have geotechnical properties similar to the LHT-2M and Chenobi regolith simulants and is being proposed as a possible simulant for geotechnical use. It currently has the designation of BP-1 (Black Point 1). Figure

  12. Preliminary Geological Findings on the BP-1 Simulant

    NASA Technical Reports Server (NTRS)

    Stoeser, D. B.; Rickman, D. L.; Wilson, S.

    2010-01-01

    A waste material from an aggregate producing quarry has been used to make an inexpensive lunar simulant called BP-1. The feedstock is the Black Point lava flow in northern Arizona. Although this is part of the San Francisco volcanic field, which is also the source of the JSC-1 series feedstock, BP-1 and JSC-1 are distinct. Chemically, the Black Point flow is an amygdaloidal nepheline-bearing basalt. The amygdules are filled with secondary minerals containing opaline silica, calcium carbonate, and ferric iron minerals. X-ray diffraction (XRD) detected approximately 3% quartz, which is in line with tests done by the Kennedy Space Center Industrial Hygiene Office. Users of this material should use appropriate protective equipment. XRD also showed the presence of significant halite and some bassanite. Both are interpreted to be evaporative residues due to recycling of wash water at the quarry. The size distribution of BP-1 may be superior to some other simulants for some applications.

  13. Broadband inversion of 1J(CC) responses in 1,n-ADEQUATE spectra.

    PubMed

    Reibarkh, Mikhail; Williamson, R Thomas; Martin, Gary E; Bermel, Wolfgang

    2013-11-01

    Establishing the carbon skeleton of a molecule greatly facilitates the process of structure elucidation, both manual and computer-assisted. Recent advances in the family of ADEQUATE experiments demonstrated their potential in this regard. 1,1-ADEQUATE, which provides direct (13)C-(13)C correlation via (1)J(CC), and 1,n-ADEQUATE, which typically yields (3)J(CC) and (1)J(CC) correlations, are more sensitive and more widely applicable experiments than INADEQUATE and PANACEA. A recently reported modified pulse sequence that semi-selectively inverts (1)J(CC) correlations in 1,n-ADEQUATE spectra provided a significant improvement, allowing (1)J(CC) and (n)J(CC) correlations to be discerned in the same spectrum. However, the reported experiment requires a careful matching of the amplitude transfer function with (1)J(CC) coupling constants in order to achieve the inversion, and even then some (1)J(CC) correlations could still have positive intensity due to the oscillatory nature of the transfer function. Both shortcomings limit the practicality of the method. We now report a new, dual-optimized inverted (1)J(CC) 1,n-ADEQUATE experiment, which provides more uniform inversion of (1)J(CC) correlations across the range of 29-82 Hz. Unlike the original method, the dual optimization experiment does not require fine-tuning for the molecule's (1)J(CC) coupling constant values. Even more usefully, the dual-optimized version provides up to two-fold improvement in signal-to-noise for some long-range correlations. Using modern, cryogenically-cooled probes, the experiment can be successfully applied to samples of ~1 mg under favorable circumstances. The improvements afforded by dual optimization inverted (1)J(CC) 1,n-ADEQUATE experiment make it a useful and practical tool for NMR structure elucidation and should facilitate the implementation and utilization of the experiment.

  14. Self-reported segregation experience throughout the life course and its association with adequate health literacy.

    PubMed

    Goodman, Melody S; Gaskin, Darrell J; Si, Xuemei; Stafford, Jewel D; Lachance, Christina; Kaphingst, Kimberly A

    2012-09-01

    Residential segregation has been shown to be associated with health outcomes and health care utilization. We examined the association between racial composition of five physical environments throughout the life course and adequate health literacy among 836 community health center patients in Suffolk County, NY. Respondents who attended a mostly White junior high school or currently lived in a mostly White neighborhood were more likely to have adequate health literacy compared to those educated or living in predominantly minority or diverse environments. This association was independent of the respondent's race, ethnicity, age, education, and country of birth.

  15. 200-BP-5 operable unit treatability test report

    SciTech Connect

    1996-04-01

    The 200-BP-5 Operable Unit was established in response to recommendations presented in the 200 East Groundwater Aggregate Area Management Study Report (AAMSR) (DOE-RL 1993a). Recognizing different approaches to remediation, the groundwater AAMSR recommended separating groundwater from source and vadose zone operable units and subdividing 200 East Area groundwater into two operable units. The division between the 200-BP-5 and 200-PO-1 Operable Units was based principally on source operable unit boundaries and distribution of groundwater plumes derived from either B Plant or Plutonium/Uranium Extraction (PUREX) Plant liquid waste disposal sites.

  16. Randomized trial of guiding hypertension management using central aortic blood pressure compared with best-practice care: principal findings of the BP GUIDE study.

    PubMed

    Sharman, James E; Marwick, Thomas H; Gilroy, Deborah; Otahal, Petr; Abhayaratna, Walter P; Stowasser, Michael

    2013-12-01

    Arm cuff blood pressure (BP) may overestimate cardiovascular risk. Central aortic BP predicts mortality and could be a better method for patient management. We sought to determine the usefulness of central BP to guide hypertension management. This was a prospective, open-label, blinded-end point study in 286 patients with hypertension randomized to treatment decisions guided by best-practice usual care (n=142; using office, home, and 24-hour ambulatory BP) or, in addition, by central BP intervention (n=144; using SphygmoCor). Therapy was reviewed every 3 months for 12 months, and recommendations were provided to each patient and his/her doctor on antihypertensive medication titration. Outcome measures were as follows: medication quantity (daily defined dose), quality of life, and left ventricular mass (3-dimensional echocardiography). There was 92% compliance with recommendations on medication titration, and quality of life improved in both groups (post hoc P<0.05). For usual care, there was no change in daily defined dose (all P>0.10), but with intervention there was a significant stepwise decrease in daily defined dose from baseline to 3 months (P=0.008) and each subsequent visit (all P<0.001). Intervention was associated with cessation of medication in 23 (16%) patients versus 3 (2%) in usual care (P<0.001). Despite this, there were no differences between groups in left ventricular mass index, 24-hour ambulatory BP, home systolic BP, or aortic stiffness (all P>0.05). We conclude that guidance of hypertension management with central BP results in a significantly different therapeutic pathway than conventional cuff BP, with less use of medication to achieve BP control and no adverse effects on left ventricular mass, aortic stiffness, or quality of life.

  17. Detection of anti-BP180NC16a and anti-BP230 autoantibodies in blister fluid of patients with bullous pemphigoid: the first survey in Greece.

    PubMed

    Patsatsi, A; Vyzantiadis, T-A; Devliotou-Panagiotidou, D; Chrysomallis, F; Sotiriadis, D

    2008-03-01

    Bullous pemphigoid (BP) is an acquired bullous disease with an increasing prevalence among elderly people worldwide, including in Greece. Blister formation in most patients with BP is caused by autoantibodies against structural components of the basement membrane zone of the skin, predominantly BP180NC16a and BP230 antigens on the hemidesmosome adhesion complex. Routine diagnostic methods such as histological examination and direct and indirect immunofluorescence are combined to determine diagnosis. In this study, an ELISA was used to measure levels of both anti-BP180NC16A and anti-BP230 autoantibodies in the blister fluid of 13 patients with newly diagnosed BP, before starting treatment. The aim of the study was to evaluate this method as a diagnostic tool in BP. Our results indicate that blister-fluid examination by ELISA can be a useful tool to diagnose bullous pemphigoid, especially in elderly patients who refuse biopsy or have poor venous access.

  18. 75 FR 5893 - Suspension of Community Eligibility for Failure To Maintain Adequate Floodplain Management...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... FR 51735. Executive Order 13132, Federalism. This rule involves no policies that have ] federalism....C. 4001 et seq., Reorganization Plan No. 3 of 1978, 3 CFR, 1978 Comp., p. 329; E.O. 12127, 44 FR... To Maintain Adequate Floodplain Management Regulations AGENCY: Federal Emergency Management...

  19. 26 CFR 1.467-2 - Rent accrual for section 467 rental agreements without adequate interest.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... interest (the stated rate of interest) on deferred or prepaid fixed rent at a single fixed rate (as defined in § 1.1273-1(c)(1)(iii)); (B) The stated rate of interest on fixed rent is no lower than 110 percent... provide for a variable rate of interest. For purposes of the adequate interest test under paragraph...

  20. Towards Defining Adequate Lithium Trials for Individuals with Mental Retardation and Mental Illness.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1991-01-01

    Use of lithium with mentally retarded individuals with psychiatric conditions and/or behavior disturbances is discussed. The paper describes components of an adequate clinical trial and reviews case studies and double-blind cases. The paper concludes that aggression is the best indicator for lithium use, and reviews treatment parameters and…

  1. How Much and What Kind? Identifying an Adequate Technology Infrastructure for Early Childhood Education. Policy Brief

    ERIC Educational Resources Information Center

    Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

    2014-01-01

    To realize the potential benefits of technology use in early childhood education (ECE), and to ensure that technology can help to address the digital divide, providers, families of young children, and young children themselves must have access to an adequate technology infrastructure. The goals for technology use in ECE that a technology…

  2. Evaluating the Reliability of Selected School-Based Indices of Adequate Reading Progress

    ERIC Educational Resources Information Center

    Wheeler, Courtney E.

    2010-01-01

    The present study examined the stability (i.e., 4-month and 12-month test-retest reliability) of six selected school-based indices of adequate reading progress. The total sampling frame included between 3970 and 5655 schools depending on the index and research question. Each school had at least 40 second-grade students that had complete Oral…

  3. Understanding the pelvic pain mechanism is key to find an adequate therapeutic approach.

    PubMed

    Van Kerrebroeck, Philip

    2016-06-25

    Pain is a natural mechanism to actual or potential tissue damage and involves both a sensory and an emotional experience. In chronic pelvic pain, localisation of pain can be widespread and can cause considerable distress. A multidisciplinary approach is needed in order to fully understand the pelvic pain mechanism and to identify an adequate therapeutic approach.

  4. 33 CFR 155.4050 - Ensuring that the salvors and marine firefighters are adequate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Ensuring that the salvors and marine firefighters are adequate. 155.4050 Section 155.4050 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION OIL OR HAZARDOUS MATERIAL POLLUTION...

  5. Performance Effects of Failure to Make Adequate Yearly Progress (AYP): Evidence from a Regression Discontinuity Framework

    ERIC Educational Resources Information Center

    Hemelt, Steven W.

    2011-01-01

    As the No Child Left Behind (NCLB) law moves through the reauthorization process, it is important to understand the basic performance impacts of its central structure of accountability. In this paper, I examine the effects of failure to make Adequate Yearly Progress (AYP) under NCLB on subsequent student math and reading performance at the school…

  6. Determining Adequate Yearly Progress in a State Performance or Proficiency Index Model

    ERIC Educational Resources Information Center

    Erpenbach, William J.

    2009-01-01

    The purpose of this paper is to present an overview regarding how several states use a performance or proficiency index in their determination of adequate yearly progress (AYP) under the No Child Left Behind Act of 2001 (NCLB). Typically, indexes are based on one of two weighting schemes: (1) either they weight academic performance levels--also…

  7. The Relationship between Parental Involvement and Adequate Yearly Progress among Urban, Suburban, and Rural Schools

    ERIC Educational Resources Information Center

    Ma, Xin; Shen, Jianping; Krenn, Huilan Y.

    2014-01-01

    Using national data from the 2007-08 School and Staffing Survey, we compared the relationships between parental involvement and school outcomes related to adequate yearly progress (AYP) in urban, suburban, and rural schools. Parent-initiated parental involvement demonstrated significantly positive relationships with both making AYP and staying off…

  8. Effect of tranquilizers on animal resistance to the adequate stimuli of the vestibular apparatus

    NASA Technical Reports Server (NTRS)

    Maksimovich, Y. B.; Khinchikashvili, N. V.

    1980-01-01

    The effect of tranquilizers on vestibulospinal reflexes and motor activity was studied in 900 centrifuged albino mice. Actometric studies have shown that the tranquilizers have a group capacity for increasing animal resistance to the action of adequate stimuli to the vestibular apparatus.

  9. Human milk feeding supports adequate growth in infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite current nutritional strategies, premature infants remain at high risk for extrauterine growth restriction. The use of an exclusive human milk-based diet is associated with decreased incidence of necrotizing enterocolitis (NEC), but concerns exist about infants achieving adequate growth. The ...

  10. [Factors associated with adequate fruit and vegetable intake by schoolchildren in Santa Catarina State, Brazil].

    PubMed

    Costa, Larissa da Cunha Feio; Vasconcelos, Francisco de Assis Guedes de; Corso, Arlete Catarina Tittoni

    2012-06-01

    This study aimed to estimate fruit and vegetable intake and identify associated factors among schoolchildren in Santa Catarina State, Brazil. A cross-sectional study was conducted with 4,964 students from public and private schools in eight districts in the State, analyzing socioeconomic and anthropometric data and dietary intake. Adequate fruit and vegetable intake was defined as five or more servings per day. Poisson regression was performed to test associations between fruit and vegetable intake and independent variables (p < 0.05). Adequate intake was found in 2.7% of children, while 26.6% of the sample did not consume any fruits and vegetables. In the analysis of the association between independent variables and adequate fruit and vegetable intake in the total sample, only geographic region (residents in western Santa Catarina) and consumption of candy were significantly associated. In the stratified analysis by sex, for boys, only geographic region was associated, while among girls, region and candy consumption were significantly associated with adequate fruit and vegetable intake. The findings indicate the need for specific strategies in the school community to improve fruit and vegetable intake by schoolchildren.

  11. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Assurances of adequate capacity and services. 438.207 Section 438.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Quality Assessment and...

  12. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Assurances of adequate capacity and services. 438.207 Section 438.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Quality Assessment and...

  13. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Assurances of adequate capacity and services. 438.207 Section 438.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Quality Assessment and...

  14. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Assurances of adequate capacity and services. 438.207 Section 438.207 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Quality Assessment and...

  15. Perceptions of Teachers in Their First Year of School Restructuring: Failure to Make Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Moser, Sharon

    2010-01-01

    The 2007-2008 school year marked the first year Florida's Title I schools that did not made Adequate Yearly Progress (AYP) for five consecutive years entered into restructuring as mandated by the "No Child Left Behind Act" of 2001. My study examines the perceptions of teacher entering into their first year of school restructuring due to failure to…

  16. The Unequal Effect of Adequate Yearly Progress: Evidence from School Visits

    ERIC Educational Resources Information Center

    Brown, Abigail B.; Clift, Jack W.

    2010-01-01

    The authors report insights, based on annual site visits to elementary and middle schools in three states from 2004 to 2006, into the incentive effect of the No Child Left Behind Act's requirement that increasing percentages of students make Adequate Yearly Progress (AYP) in every public school. They develop a framework, drawing on the physics…

  17. Influenza 2005-2006: vaccine supplies adequate, but bird flu looms.

    PubMed

    Mossad, Sherif B

    2005-11-01

    Influenza vaccine supplies appear to be adequate for the 2005-2006 season, though delivery has been somewhat delayed. However, in the event of a pandemic of avian flu-considered inevitable by most experts, although no one knows when it will happen-the United States would be woefully unprepared. PMID:16315443

  18. Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

  19. Inferential Processing among Adequate and Struggling Adolescent Comprehenders and Relations to Reading Comprehension

    ERIC Educational Resources Information Center

    Barth, Amy E.; Barnes, Marcia; Francis, David; Vaughn, Sharon; York, Mary

    2015-01-01

    Separate mixed model analyses of variance were conducted to examine the effect of textual distance on the accuracy and speed of text consistency judgments among adequate and struggling comprehenders across grades 6-12 (n = 1,203). Multiple regressions examined whether accuracy in text consistency judgments uniquely accounted for variance in…

  20. What Is the Cost of an Adequate Vermont High School Education?

    ERIC Educational Resources Information Center

    Rucker, Frank D.

    2010-01-01

    Access to an adequate education has been widely considered an undeniable right since Chief Justice Warren stated in his landmark decision that "Today, education is perhaps the most important function of state and local governments...it is doubtful that any child may reasonably be expected to succeed in life if he is denied the opportunity of an…

  1. Calculating and Reducing Errors Associated with the Evaluation of Adequate Yearly Progress.

    ERIC Educational Resources Information Center

    Hill, Richard

    In the Spring, 1996, issue of "CRESST Line," E. Baker and R. Linn commented that, in efforts to measure the progress of schools, "the fluctuations due to differences in the students themselves could conceal differences in instructional effects." This is particularly true in the context of the evaluation of adequate yearly progress required by…

  2. 26 CFR 1.467-2 - Rent accrual for section 467 rental agreements without adequate interest.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... provide for a variable rate of interest. For purposes of the adequate interest test under paragraph (b)(1) of this section, if a section 467 rental agreement provides for variable interest, the rental... date as the issue date) for the variable rates called for by the rental agreement. For purposes of...

  3. 26 CFR 1.467-2 - Rent accrual for section 467 rental agreements without adequate interest.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... provide for a variable rate of interest. For purposes of the adequate interest test under paragraph (b)(1) of this section, if a section 467 rental agreement provides for variable interest, the rental... date as the issue date) for the variable rates called for by the rental agreement. For purposes of...

  4. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  5. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  6. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Attending veterinarian and adequate veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian...

  7. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  8. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  9. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Attending veterinarian and adequate veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian...

  10. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Attending veterinarian and adequate veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian...

  11. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Attending veterinarian and adequate veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian...

  12. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Attending veterinarian and adequate veterinary care (dealers and exhibitors). 2.40 Section 2.40 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Attending...

  13. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Attending veterinarian and adequate veterinary care. 2.33 Section 2.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.33 Attending veterinarian...

  14. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Who determines when there is adequate snow cover? 13.960 Section 13.960 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Denali National Park...

  15. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Adequate financial records, statistical data, and... financial records, statistical data, and cost finding. (a) Maintenance of records. (1) An HMO or CMP must maintain sufficient financial records and statistical data for proper determination of costs payable by...

  16. Multi-Functional Regulation of 4E-BP Gene Expression by the Ccr4-Not Complex

    PubMed Central

    Okada, Hirokazu; Schittenhelm, Ralf B.; Straessle, Anna; Hafen, Ernst

    2015-01-01

    The mechanistic target of rapamycin (mTOR) signaling pathway is highly conserved from yeast to humans. It senses various environmental cues to regulate cellular growth and homeostasis. Deregulation of the pathway has been implicated in many pathological conditions including cancer. Phosphorylation cascades through the pathway have been extensively studied but not much is known about the regulation of gene expression of the pathway components. Here, we report that the mRNA level of eukaryotic translation initiation factor (eIF) subunit 4E-binding protein (4E-BP) gene, one of the key mTOR signaling components, is regulated by the highly conserved Ccr4-Not complex. RNAi knockdown of Not1, a putative scaffold protein of this protein complex, increases the mRNA level of 4E-BP in Drosophila Kc cells. Examination of the gene expression mechanism using reporter swap constructs reveals that Not1 depletion increases reporter mRNAs with the 3’UTR of 4E-BP gene, but decreases the ones with the 4E-BP promoter region, suggesting that Ccr4-Not complex regulates both degradation and transcription of 4E-BP mRNA. These results indicate that the Ccr4-Not complex controls expression of a single gene at multiple levels and adjusts the magnitude of the total effect. Thus, our study reveals a novel regulatory mechanism of a key component of the mTOR signaling pathway at the level of gene expression. PMID:25793896

  17. Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

    PubMed Central

    Chen, Fenfang; Lin, Xia; Xu, Pinglong; Zhang, Zhengmao; Chen, Yanzhen; Wang, Chao; Han, Jiahuai; Zhao, Bin; Xiao, Mu

    2015-01-01

    Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation. PMID:25755279

  18. BP chief scientist nominated for senior energy role

    NASA Astrophysics Data System (ADS)

    Gwynne, Peter

    2014-01-01

    The Obama administration has nominated BP's chief scientist Ellen Williams to be director of the Advanced Research Projects Agency-Energy (ARPA-E), which was created in 2007 to fund "high-risk, high-reward" research into novel energy technologies that are too early for investment by the private sector.

  19. TopBP1-mediated DNA processing during mitosis.

    PubMed

    Gallina, Irene; Christiansen, Signe Korbo; Pedersen, Rune Troelsgaard; Lisby, Michael; Oestergaard, Vibe H

    2016-01-01

    Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells. (1) Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases.

  20. [The global and national context regarding the challenges involved in ensuring adequate access to water for human consumption].

    PubMed

    Augusto, Lia Giraldo da Silva; Gurgel, Idê Gomes Dantas; Câmara Neto, Henrique Fernandes; de Melo, Carlos Henrique; Costa, André Monteiro

    2012-06-01

    The scope of this article is to analyze the challenges involved in ensuring access to water for human consumption taking the international and national context into consideration. Based on the UN declaration that access to safe and clean drinking water is a fundamental human right, vulnerabilities are identified that can consist in restrictions to access to adequate supplies. The distribution of water and the population across the planet, pollution, inadequate policies and management lead to environmental injustice. The iniquity of access to water constitutes the contemporary water crisis. From the 1980s onwards, the transnational water market emerged for private control that occurs at three main levels: surface and underground water sources; bottled water; and public water supply services. The conflicts of the multiple uses of water resources, the market and environmental problems have contributed to rendering the health of the population and ecosystems vulnerable. Adequate public policies are essential to ensure the basic human right to access to safe and clean drinking water.

  1. Ensuring smokers are adequately informed: reflections on consumer rights, manufacturer responsibilities, and policy implications

    PubMed Central

    Chapman, S; Liberman, J

    2005-01-01

    The right to information is a fundamental consumer value. Following the advent of health warnings, the tobacco industry has repeatedly asserted that smokers are fully informed of the risks they take, while evidence demonstrates widespread superficial levels of awareness and understanding. There remains much that tobacco companies could do to fulfil their responsibilities to inform smokers. We explore issues involved in the meaning of "adequately informed" smoking and discuss some of the key policy and regulatory implications. We use the idea of a smoker licensing scheme—under which it would be illegal to sell to smokers who had not demonstrated an adequate level of awareness—as a device to explore some of these issues. We also explore some of the difficulties that addiction poses for the notion that smokers might ever voluntarily assume the risks of smoking. PMID:16046703

  2. The concept of adequate causation and Max Weber's comparative sociology of religion.

    PubMed

    Buss, A

    1999-06-01

    Max Weber's The Protestant Ethic and the Spirit of Capitalism, studied in isolation, shows mainly an elective affinity or an adequacy on the level of meaning between the Protestant ethic and the 'spirit' of capitalism. Here it is suggested that Weber's subsequent essays on 'The Economic Ethics of World Religions' are the result of his opinion that adequacy on the level of meaning needs and can be verified by causal adequacy. After some introductory remarks, particularly on elective affinity, the paper tries to develop the concept of adequate causation and the related concept of objective possibility on the basis of the work of v. Kries on whom Weber heavily relied. In the second part, this concept is used to show how the study of the economic ethics of India, China, Rome and orthodox Russia can support the thesis that the 'spirit' of capitalism, although it may not have been caused by the Protestant ethic, was perhaps adequately caused by it. PMID:15260028

  3. Ensuring smokers are adequately informed: reflections on consumer rights, manufacturer responsibilities, and policy implications.

    PubMed

    Chapman, S; Liberman, J

    2005-08-01

    The right to information is a fundamental consumer value. Following the advent of health warnings, the tobacco industry has repeatedly asserted that smokers are fully informed of the risks they take, while evidence demonstrates widespread superficial levels of awareness and understanding. There remains much that tobacco companies could do to fulfil their responsibilities to inform smokers. We explore issues involved in the meaning of "adequately informed" smoking and discuss some of the key policy and regulatory implications. We use the idea of a smoker licensing scheme-under which it would be illegal to sell to smokers who had not demonstrated an adequate level of awareness-as a device to explore some of these issues. We also explore some of the difficulties that addiction poses for the notion that smokers might ever voluntarily assume the risks of smoking. PMID:16046703

  4. Myth 19: Is Advanced Placement an Adequate Program for Gifted Students?

    ERIC Educational Resources Information Center

    Gallagher, Shelagh A.

    2009-01-01

    Is it a myth that Advanced Placement (AP) is an adequate program for gifted students? AP is so covered with myths and assumptions that it is hard to get a clear view of the issues. In this article, the author finds the answer about AP by looking at current realties. First, AP is hard for gifted students to avoid. Second, AP never was a program…

  5. Small molecule, NSC95397, inhibits the CtBP1-protein partner interaction and CtBP1-mediated transcriptional repression

    PubMed Central

    Blevins, Melanie A.; Kouznetsova, Jennifer; Krueger, Aaron B.; King, Rebecca; Griner, Lesley Mathews; Hu, Xin; Southall, Noel; Marugan, Juan J.; Ferrer, Marc

    2015-01-01

    Carboxyl-terminal binding protein (CtBP) is a transcriptional co-repressor that suppresses multiple pro-apoptotic and epithelial genes. CtBP is overexpressed in many human cancers and its overexpression increases stem cell-like features, epithelial-mesenchymal transition, and cancer cell survival. Knockdown of CtBP increases apoptosis independent of p53 and dramatically inhibits tumorigenesis in mouse models. Therefore, targeting CtBP with small molecules that disrupt its interaction with transcription factor partners may be an effective cancer therapy. To elicit its co-repressing effect, CtBP binds to a conserved peptide motif in each transcription factor partner. We developed an AlphaScreen high throughput screening assay to monitor the interaction between CtBP and E1A (which mimics the interaction between CtBP and its transcriptional partners). We screened the LOPAC library of 1280 bioactive compounds and identified NSC95397, which inhibits the CtBP-E1A interaction (IC50 = 2.9 μM). The inhibitory activity of NSC95397 was confirmed using two secondary assays and a counterscreen. NSC95397 also behaved as a weak substrate of CtBP dehydrogenase activity and did not inhibit another dehydrogenase, LDH. Finally, NSC95397 was able to disrupt CtBP-mediated transcriptional repression of a target gene. These studies present a new possibility for the development of a therapeutic agent targeting tumors through disrupting the CtBP transcriptional complex. PMID:25477201

  6. Bioelement effects on thyroid gland in children living in iodine-adequate territory.

    PubMed

    Gorbachev, Anatoly L; Skalny, Anatoly V; Koubassov, Roman V

    2007-01-01

    Endemic goitre is a primary pathology of thyroid gland and critical medico social problem in many countries. A dominant cause of endemic goitre is iodine deficiency. However, besides primary iodine deficiency, the goitre may probably develop due to effects of other bioelement imbalances, essential to thyroid function maintenance. Here we studied 44 cases of endemic goitre in prepubertal children (7-10 y.o.) living in iodine-adequate territory. Thyroid volume was estimated by ultrasonometry. Main bioelements (Al, Ca, Cd, Co, Cr, Cu, Fe, Hg, I, Mg, Mn, Pb, Se, Si, Zn) were determined in hair samples by ICP-OES/ICP-MS method. Relationships between hair content of bioelements and thyroid gland size were estimated by multiple regressions. The regression model revealed significant positive relations between thyroid volume and Cr, Si, Mn contents. However, the actual factor of thyroid gland increase was only Si excess in organism. Significant negative relations of thyroid volume were revealed with I, Mg, Zn, Se, Co and Cd. In spite of this, the actual factors of thyroid gland volume increasing were I, Co, Mg and Se deficiency. Total bioelement contribution in thyroid impairment was estimated as 24%. Thus, it was suggested that endemic goitre in iodine-adequate territory can be formed by bioelement imbalances, namely Si excess and Co, Mg, Se shortage as well as endogenous I deficiency in spite of iodine-adequate environment.

  7. Global Risk Assessment of Aflatoxins in Maize and Peanuts: Are Regulatory Standards Adequately Protective?

    PubMed Central

    Wu, Felicia

    2013-01-01

    The aflatoxins are a group of fungal metabolites that contaminate a variety of staple crops, including maize and peanuts, and cause an array of acute and chronic human health effects. Aflatoxin B1 in particular is a potent liver carcinogen, and hepatocellular carcinoma (HCC) risk is multiplicatively higher for individuals exposed to both aflatoxin and chronic infection with hepatitis B virus (HBV). In this work, we sought to answer the question: do current aflatoxin regulatory standards around the world adequately protect human health? Depending upon the level of protection desired, the answer to this question varies. Currently, most nations have a maximum tolerable level of total aflatoxins in maize and peanuts ranging from 4 to 20ng/g. If the level of protection desired is that aflatoxin exposures would not increase lifetime HCC risk by more than 1 in 100,000 cases in the population, then most current regulatory standards are not adequately protective even if enforced, especially in low-income countries where large amounts of maize and peanuts are consumed and HBV prevalence is high. At the protection level of 1 in 10,000 lifetime HCC cases in the population, however, almost all aflatoxin regulations worldwide are adequately protective, with the exception of several nations in Africa and Latin America. PMID:23761295

  8. Global risk assessment of aflatoxins in maize and peanuts: are regulatory standards adequately protective?

    PubMed

    Wu, Felicia; Stacy, Shaina L; Kensler, Thomas W

    2013-09-01

    The aflatoxins are a group of fungal metabolites that contaminate a variety of staple crops, including maize and peanuts, and cause an array of acute and chronic human health effects. Aflatoxin B1 in particular is a potent liver carcinogen, and hepatocellular carcinoma (HCC) risk is multiplicatively higher for individuals exposed to both aflatoxin and chronic infection with hepatitis B virus (HBV). In this work, we sought to answer the question: do current aflatoxin regulatory standards around the world adequately protect human health? Depending upon the level of protection desired, the answer to this question varies. Currently, most nations have a maximum tolerable level of total aflatoxins in maize and peanuts ranging from 4 to 20ng/g. If the level of protection desired is that aflatoxin exposures would not increase lifetime HCC risk by more than 1 in 100,000 cases in the population, then most current regulatory standards are not adequately protective even if enforced, especially in low-income countries where large amounts of maize and peanuts are consumed and HBV prevalence is high. At the protection level of 1 in 10,000 lifetime HCC cases in the population, however, almost all aflatoxin regulations worldwide are adequately protective, with the exception of several nations in Africa and Latin America.

  9. An adequate Fe nutritional status of maize suppresses infection and biotrophic growth of Colletotrichum graminicola.

    PubMed

    Ye, Fanghua; Albarouki, Emad; Lingam, Brahmasivasenkar; Deising, Holger B; von Wirén, Nicolaus

    2014-07-01

    Iron (Fe) is an essential element for plant pathogens as well as for their host plants. As Fe plays a central role in pathogen virulence, most plants have evolved Fe-withholding strategies to reduce Fe availability to pathogens. On the other hand, plants need Fe for an oxidative burst in their basal defense response against pathogens. To investigate how the plant Fe nutritional status affects plant tolerance to a hemibiotrophic fungal pathogen, we employed the maize-Colletotrichum graminicola pathosystem. Fungal infection progressed rapidly via biotrophic to necrotrophic growth in Fe-deficient leaves, while an adequate Fe nutritional status suppressed the formation of infection structures of C. graminicola already during the early biotrophic growth phase. As indicated by Prussian blue and 3,3'-diaminobenzidine (DAB) staining, the retarding effect of an adequate Fe nutritional status on fungal development coincided temporally and spatially with the recruitment of Fe to infection sites and a local production of H2 O2 . A similar coincidence between local Fe and H2 O2 accumulation was found in a parallel approach employing C. graminicola mutants affected in Fe acquisition and differing in virulence. These results indicate that an adequate Fe nutritional status delays and partially suppresses the fungal infection process and the biotrophic growth phase of C. graminicola, most likely via the recruitment of free Fe to the fungal infection site for a timely oxidative burst.

  10. Nutraceuticals for blood pressure control.

    PubMed

    Sirtori, Cesare R; Arnoldi, Anna; Cicero, Arrigo F G

    2015-01-01

    Significant effects on blood pressure (BP) have been reported from large nutritional interventions, particularly the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet. In more recent years, numerous studies have investigated the possible BP-lowering effect of different nutraceuticals; these range from specific foods to minerals, lipids, whole proteins, peptides, amino acids, probiotics, and vitamins. While a very large body of evidence supports the use of potassium, L-arginine, vitamins C and D, cocoa flavonoids, beetroot juice, some probiotics, coenzyme Q10, controlled-release melatonin, aged garlic extract, and coffee, the use of other nutraceuticals, such as green tea, flaxseed, and resveratrol, has not as yet been supported by adequate evidence. In some cases, e.g. proteins/peptides, the responsible component needs also to be fully uncovered. Finally, while for most of the products only short-term studies are available, with no specific end-points, an ongoing very large prospective study on chocolate flavanols will answer the question whether this may reduce cardiovascular risk. Thus, in addition to data on long-term safety, further clinical research is advisable in order to identify, among active nutraceuticals, those with the best cost-effectiveness and risk-benefit ratio for a wide use in the general population with a raised cardiovascular risk consequent to uncomplicated hypertension. PMID:26362125

  11. Muscle-specific 4E-BP1 signaling activation improves metabolic parameters during aging and obesity

    PubMed Central

    Tsai, Shihyin; Sitzmann, Joanna M.; Dastidar, Somasish G.; Rodriguez, Ariana A.; Vu, Stephanie L.; McDonald, Circe E.; Academia, Emmeline C.; O’Leary, Monique N.; Ashe, Travis D.; La Spada, Albert R.; Kennedy, Brian K.

    2015-01-01

    Eukaryotic translation initiation factor 4E–binding protein 1 (4E-BP1) is a key downstream effector of mTOR complex 1 (mTORC1) that represses cap-dependent mRNA translation initiation by sequestering the translation initiation factor eIF4E. Reduced mTORC1 signaling is associated with life span extension and improved metabolic homeostasis, yet the downstream targets that mediate these benefits are unclear. Here, we demonstrated that enhanced 4E-BP1 activity in mouse skeletal muscle protects against age- and diet-induced insulin resistance and metabolic rate decline. Transgenic animals displayed increased energy expenditure; altered adipose tissue distribution, including reduced white adipose accumulation and preserved brown adipose mass; and were protected from hepatic steatosis. Skeletal muscle–specific 4E-BP1 mediated metabolic protection directly through increased translation of peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) and enhanced respiratory function. Non–cell autonomous protection was through preservation of brown adipose tissue metabolism, which was increased in 4E-BP1 transgenic animals during normal aging and in a response to diet-induced type 2 diabetes. Adipose phenotypes may derive from enhanced skeletal muscle expression and secretion of the known myokine FGF21. Unlike skeletal muscle, enhanced adipose-specific 4E-BP1 activity was not protective but instead was deleterious in response to the same challenges. These findings indicate that regulation of 4E-BP1 in skeletal muscle may serve as an important conduit through which mTORC1 controls metabolism. PMID:26121750

  12. The translational repressor eIF4E-binding protein 2 (4E-BP2) correlates with selective delayed neuronal death after ischemia

    PubMed Central

    Ayuso, María Irene; Martínez-Alonso, Emma; Cid, Cristina; de Leciñana, Maria Alonso; Alcázar, Alberto

    2013-01-01

    Transient brain ischemia induces an inhibition of translational rates and causes delayed neuronal death in selective regions and cognitive deficits, whereas these effects do not occur in resistant areas. The translational repressor eukaryotic initiation factor (eIF) 4E-binding protein-2 (4E-BP2) specifically binds to eIF4E and is critical in the control of protein synthesis. To link neuronal death to translation inhibition, we study the eIF4E association with 4E-BP2 under ischemia reperfusion in a rat model of transient forebrain ischemia. Upon reperfusion, a selective neuronal apoptosis in the hippocampal cornu ammonis 1 (CA1) region was induced, while it did not occur in the cerebral cortex. Confocal microscopy analysis showed a decrease in 4E-BP2/eIF4E colocalization in resistant cortical neurons after reperfusion. In contrast, in vulnerable CA1 neurons, 4E-BP2 remains associated to eIF4E with a higher degree of 4E-BP2/eIF4E colocalization and translation inhibition. Furthermore, the binding of a 4E-BP2 peptide to eIF4E induced neuronal apoptosis in the CA1 region. Finally, pharmacological-induced protection of CA1 neurons inhibited neuronal apoptosis, decreased 4E-BP2/eIF4E association, and recovered translation. These findings documented specific changes in 4E-BP2/eIF4E association during ischemic reperfusion, linking the translation inhibition to selective neuronal death, and identifying 4E-BP2 as a novel target for protection of vulnerable neurons in ischemic injury. PMID:23591646

  13. Calibration of the radiocarbon time scale at 37ka BP

    SciTech Connect

    Southon, J.R.; Deino, A.L.; Orsi, G.

    1995-12-01

    Results from radiocarbon and U-Th measurements on corals have provided a radiocarbon calibration beyond the range covered by tree ring series, but the uncertainties in the measurements beyond 20ka BP are very large. We have obtained new calibration data from radiocarbon dates on material associated with the catastrophic Campanian Ignimbrite eruption from the Phlegrean Fields near Naples. The eruption has been well dated by {sup 40}Ar/{sup 39}Ar to 37ka BP. Radiocarbon measurements were carried out on charcoal from a carbonized branch exposed within the ignimbrite tuff on the wall of an active quarry. The sample was split and analyzed at both the Naples and Lawrence Livermore AMS facilities. The offset between the Ar-Ar data and the radiocarbon results (recalculated using the true 5730-year half life for {sup 14}C) is consistent with predictions from paleomagnetic data and carbon cycle modeling.

  14. Magnetospheric accretion on the T Tauri star BP Tauri

    NASA Astrophysics Data System (ADS)

    Donati, J.-F.; Jardine, M. M.; Gregory, S. G.; Petit, P.; Paletou, F.; Bouvier, J.; Dougados, C.; Ménard, F.; Collier Cameron, A.; Harries, T. J.; Hussain, G. A. J.; Unruh, Y.; Morin, J.; Marsden, S. C.; Manset, N.; Aurière, M.; Catala, C.; Alecian, E.

    2008-05-01

    From observations collected with the ESPaDOnS and NARVAL spectropolarimeters, we report the detection of Zeeman signatures on the classical T Tauri star (cTTS) BP Tau. Circular polarization signatures in photospheric lines and in narrow emission lines tracing magnetospheric accretion are monitored throughout most of the rotation cycle of BP Tau at two different epochs in 2006. We observe that rotational modulation dominates the temporal variations of both unpolarized and circularly polarized spectral proxies tracing the photosphere and the footpoints of accretion funnels. From the complete data sets at each epoch, we reconstruct the large-scale magnetic topology and the location of accretion spots at the surface of BP Tau using tomographic imaging. We find that the field of BP Tau involves a 1.2 kG dipole and 1.6 kG octupole, both slightly tilted with respect to the rotation axis. Accretion spots coincide with the two main magnetic poles at high latitudes and overlap with dark photospheric spots; they cover about 2 per cent of the stellar surface. The strong mainly axisymmetric poloidal field of BP Tau is very reminiscent of magnetic topologies of fully convective dwarfs. It suggests that magnetic fields of fully convective cTTSs such as BP Tau are likely not fossil remants, but rather result from vigorous dynamo action operating within the bulk of their convective zones. Preliminary modelling suggests that the magnetosphere of BP Tau extends to distances of at least 4R* to ensure that accretion spots are located at high latitudes, and is not blown open close to the surface by a putative stellar wind. It apparently succeeds in coupling to the accretion disc as far out as the corotation radius, and could possibly explain the slow rotation of BP Tau. Based on observations obtained at the Canada-France-Hawaii Telescope (CFHT) and at the Télescope Bernard Lyot (TBL). CFHT is operated by the National Research Council of Canada, the Institut National des Sciences de l

  15. Variability of Balmer Profiles in Magnetic Ap/Bp Stars

    NASA Astrophysics Data System (ADS)

    Valyavin, G.; Lee, B.-C.; Shulyak, D.; Han, I.; Kochukhov, O.; Khang, D.-I.; Kim, K.-M.

    2007-06-01

    A set of high precision measurements of weak variations of hydrogen lines in spectra of seven magnetic Ap/Bp stars was carried out using the BOES echelle spectrograph of the Bohuynsan Optical Astronomy Observatory (South Korea). A weak (1-2 %) periodic variability of the Balmer line wings has been detected in the spectra of 2 program stars. Upper limits of possible variations are presented for the remaining 5 objects. We discuss the discovered variability in the framework of model atmospheres with magnetic force terms included. The periodic changes in the Balmer profiles are caused by perturbations in atmospheres of Ap/Bp stars due to their rotationally modulated non-force-free magnetic fields.

  16. Diffusion and Settling in Ap/Bp Stars

    SciTech Connect

    Turcotte, S

    2003-04-09

    Ap/Bp stars are magnetic chemically peculiar early A and late B type stars of the main sequence. They exhibit peculiar surface abundance anomalies that are thought to be the result of gravitational settling and radiative levitation. The physics of diffusion in these stars are reviewed briefly and some model predictions are discussed. While models reproduce some observations reasonably well, more work is needed before the behavior of diffusing elements in a complex magnetic field is fully understood.

  17. Adequate Iodine Status in New Zealand School Children Post-Fortification of Bread with Iodised Salt.

    PubMed

    Jones, Emma; McLean, Rachael; Davies, Briar; Hawkins, Rochelle; Meiklejohn, Eva; Ma, Zheng Feei; Skeaff, Sheila

    2016-01-01

    Iodine deficiency re-emerged in New Zealand in the 1990s, prompting the mandatory fortification of bread with iodised salt from 2009. This study aimed to determine the iodine status of New Zealand children when the fortification of bread was well established. A cross-sectional survey of children aged 8-10 years was conducted in the cities of Auckland and Christchurch, New Zealand, from March to May 2015. Children provided a spot urine sample for the determination of urinary iodine concentration (UIC), a fingerpick blood sample for Thyroglobulin (Tg) concentration, and completed a questionnaire ascertaining socio-demographic information that also included an iodine-specific food frequency questionnaire (FFQ). The FFQ was used to estimate iodine intake from all main food sources including bread and iodised salt. The median UIC for all children (n = 415) was 116 μg/L (females 106 μg/L, males 131 μg/L) indicative of adequate iodine status according to the World Health Organisation (WHO, i.e., median UIC of 100-199 μg/L). The median Tg concentration was 8.7 μg/L, which was <10 μg/L confirming adequate iodine status. There was a significant difference in UIC by sex (p = 0.001) and ethnicity (p = 0.006). The mean iodine intake from the food-only model was 65 μg/day. Bread contributed 51% of total iodine intake in the food-only model, providing a mean iodine intake of 35 μg/day. The mean iodine intake from the food-plus-iodised salt model was 101 μg/day. In conclusion, the results of this study confirm that the iodine status in New Zealand school children is now adequate. PMID:27196925

  18. Adequate Iodine Status in New Zealand School Children Post-Fortification of Bread with Iodised Salt

    PubMed Central

    Jones, Emma; McLean, Rachael; Davies, Briar; Hawkins, Rochelle; Meiklejohn, Eva; Ma, Zheng Feei; Skeaff, Sheila

    2016-01-01

    Iodine deficiency re-emerged in New Zealand in the 1990s, prompting the mandatory fortification of bread with iodised salt from 2009. This study aimed to determine the iodine status of New Zealand children when the fortification of bread was well established. A cross-sectional survey of children aged 8–10 years was conducted in the cities of Auckland and Christchurch, New Zealand, from March to May 2015. Children provided a spot urine sample for the determination of urinary iodine concentration (UIC), a fingerpick blood sample for Thyroglobulin (Tg) concentration, and completed a questionnaire ascertaining socio-demographic information that also included an iodine-specific food frequency questionnaire (FFQ). The FFQ was used to estimate iodine intake from all main food sources including bread and iodised salt. The median UIC for all children (n = 415) was 116 μg/L (females 106 μg/L, males 131 μg/L) indicative of adequate iodine status according to the World Health Organisation (WHO, i.e., median UIC of 100–199 μg/L). The median Tg concentration was 8.7 μg/L, which was <10 μg/L confirming adequate iodine status. There was a significant difference in UIC by sex (p = 0.001) and ethnicity (p = 0.006). The mean iodine intake from the food-only model was 65 μg/day. Bread contributed 51% of total iodine intake in the food-only model, providing a mean iodine intake of 35 μg/day. The mean iodine intake from the food-plus-iodised salt model was 101 μg/day. In conclusion, the results of this study confirm that the iodine status in New Zealand school children is now adequate. PMID:27196925

  19. Thrombography reveals thrombin generation potential continues to deteriorate following cardiopulmonary bypass surgery despite adequate hemostasis.

    PubMed

    Wong, Raymond K; Sleep, Joseph R; Visner, Allison J; Raasch, David J; Lanza, Louis A; DeValeria, Patrick A; Torloni, Antonio S; Arabia, Francisco A

    2011-03-01

    The intrinsic and extrinsic activation pathways of the hemostatic system converge when prothrombin is converted to thrombin. The ability to generate an adequate thrombin burst is the most central aspect of the coagulation cascade. The thrombin-generating potential in patients following cardiopulmonary bypass (CPB) may be indicative of their hemostatic status. In this report, thrombography, a unique technique for directly measuring the potential of patients' blood samples to generate adequate thrombin bursts, is used to characterize the coagulopathic profile in post-CPB patients. Post-CPB hemostasis is typically achieved with protamine reversal of heparin anticoagulation and occasionally supplemented with blood product component transfusions. In this pilot study, platelet poor plasma samples were derived from 11 primary cardiac surgery patients at five time points: prior to CPB, immediately post-protamine, upon arrival to the intensive care unit (ICU), 3 hours post-ICU admission, and 24 hours after ICU arrival. Thrombography revealed that the Endogenous Thrombin Potential (ETP) was not different between [Baseline] and [PostProtamine] but proceeded to deteriorate in the immediate postoperative period. At the [3HourPostICU] time point, the ETP was significantly lower than the [Baseline] values, 1233 +/- 591 versus 595 +/- 379 nM.min (mean +/- SD; n=9, p < .005), despite continued adequacy of hemostasis. ETPs returned to baseline values the day after surgery. Transfusions received, conventional blood coagulation testing results, and blood loss volumes are also presented. Despite adequate hemostasis, thrombography reveals an underlying coagulopathic process that could put some cardiac surgical patients at risk for postoperative bleeding. Thrombography is a novel technique that could be developed into a useful tool for perfusionists and physicians to identify coagulopathies and optimize blood management following CPB. PMID:21449230

  20. Chronic leg ulcer: does a patient always get a correct diagnosis and adequate treatment?

    PubMed

    Mooij, Michael C; Huisman, Laurens C

    2016-03-01

    Patients with chronic leg ulcers have severely impaired quality of life and account for a high percentage of annual healthcare costs. To establish the cause of a chronic leg ulcer, referral to a center with a multidisciplinary team of professionals is often necessary. Treating the underlying cause diminishes healing time and reduces costs. In venous leg ulcers adequate compression therapy is still a problem. It can be improved by training the professionals with pressure measuring devices. A perfect fitting of elastic stockings is important to prevent venous leg ulcer recurrence. In most cases, custom-made stockings are the best choice for this purpose. PMID:26916772

  1. Nebulized antibiotics. An adequate option for treating ventilator-associated respiratory infection?

    PubMed

    Rodríguez, A; Barcenilla, F

    2015-03-01

    Ventilator-associated tracheobronchitis (VAT) is a frequent complication in critical patients. The 90% of those who develop it receive broad-spectrum antibiotic (ATB) treatment, without any strong evidence of its favorable impact. The use of nebulized ATB could be a valid treatment option, to reduce the use of systemic ATB and the pressure of selection on the local flora. Several studies suggest that an adequate nebulization technique can ensure high levels of ATB even in areas of lung consolidation, and to obtain clinical and microbiological cure. New studies are needed to properly assess the impact of treatment with nebulized ATB on the emergence of resistance.

  2. Developing an adequate "pneumatraumatology": understanding the spiritual impacts of traumatic injury.

    PubMed

    Bidwell, Duane R

    2002-01-01

    Psychosocial interventions and systematic theology are primary resources for chaplains and congregational pastors who care for victims of physical trauma. Yet these resources may not be adequate to address the spiritual impacts of trauma. This article proposes a preliminary "pneumatraumatology," drawing on early Christian asceticism and Buddhist mysticism to describe one way of understanding the spiritual impacts of traumatic injury. It also suggests possible responses to these impacts informed by narrative/constructionist perspectives and Breggemann's understanding of the dimensions of spiritual transformation in the Hebrew Bible.

  3. Optimal detection pinhole for lowering speckle noise while maintaining adequate optical sectioning in confocal reflectance microscopes.

    PubMed

    Glazowski, Christopher; Rajadhyaksha, Milind

    2012-08-01

    Coherent speckle influences the resulting image when narrow spectral line-width and single spatial mode illumination are used, though these are the same light-source properties that provide the best radiance-to-cost ratio. However, a suitable size of the detection pinhole can be chosen to maintain adequate optical sectioning while making the probability density of the speckle noise more normal and reducing its effect. The result is a qualitatively better image with improved contrast, which is easier to read. With theoretical statistics and experimental results, we show that the detection pinhole size is a fundamental parameter for designing imaging systems for use in turbid media.

  4. [Functional restoration--it depends on an adequate mixture of treatment].

    PubMed

    Pfingsten, M

    2001-12-01

    In the last 50 years conventional treatments have not been able to slow down the expanding chronic low back pain problem. However, nowadays health care has changed according to a broad biopsychosocial model of health, the positive effect of activity on health and healing, emphasis on function rather than pain or impairment, and reliance upon clinical evidence. In search for new solutions "functional restoration" (FR) programs have been developed. They include multidisciplinary treatment of patients in groups, consisting of 6-8 h of treatment a day, lasting 3 to 6 weeks and usually integrating intense physical and ergonomic training, psychological (behavioral) therapy, patient education, and instruction in social- and work-related issues. FR programs have yet to demonstrate their effectiveness in several countries. Controlled studies in the USA were very positive regarding the return-to-work rate, whereas studies in Scandinavian countries did not demonstrate similar results. Possible reasons for the different results concerning back-to-work ratios might be that study design, patient population, content of the program, and other external factors are different and studies as well as effects are therefore not directly comparable. According to several well-controlled studies, the most probable reason for this different effect may be that social and security (health care) systems and cultures differ among countries and that patients with chronic low back pain respond differently to this combination. Sick absenteeism and inability to work may be influenced by many factors besides pain that cannot be addressed by intervention or prevention programs, e.g., job satisfaction, education level, and the compensation systems. It may be that the lower economic benefit during sick leave in the United States leads to favorable results from functional restoration programs. Concerning the prediction of success, several studies have shown that medical background, diagnosis and physical

  5. [Functional restoration--it depends on an adequate mixture of treatment].

    PubMed

    Pfingsten, M

    2001-12-01

    In the last 50 years conventional treatments have not been able to slow down the expanding chronic low back pain problem. However, nowadays health care has changed according to a broad biopsychosocial model of health, the positive effect of activity on health and healing, emphasis on function rather than pain or impairment, and reliance upon clinical evidence. In search for new solutions "functional restoration" (FR) programs have been developed. They include multidisciplinary treatment of patients in groups, consisting of 6-8 h of treatment a day, lasting 3 to 6 weeks and usually integrating intense physical and ergonomic training, psychological (behavioral) therapy, patient education, and instruction in social- and work-related issues. FR programs have yet to demonstrate their effectiveness in several countries. Controlled studies in the USA were very positive regarding the return-to-work rate, whereas studies in Scandinavian countries did not demonstrate similar results. Possible reasons for the different results concerning back-to-work ratios might be that study design, patient population, content of the program, and other external factors are different and studies as well as effects are therefore not directly comparable. According to several well-controlled studies, the most probable reason for this different effect may be that social and security (health care) systems and cultures differ among countries and that patients with chronic low back pain respond differently to this combination. Sick absenteeism and inability to work may be influenced by many factors besides pain that cannot be addressed by intervention or prevention programs, e.g., job satisfaction, education level, and the compensation systems. It may be that the lower economic benefit during sick leave in the United States leads to favorable results from functional restoration programs. Concerning the prediction of success, several studies have shown that medical background, diagnosis and physical

  6. Technical basis for flawed cylinder test specification to assure adequate fracture resistance of ISO high strength steel cylinder

    SciTech Connect

    Rana, M.D.; Smith, J.H.; Tribolet, R.O.

    1996-12-01

    High pressure industrial gases (such as oxygen, nitrogen, argon, hydrogen, etc.) are stored and transported in portable cylinders. ISO TC58 SC3 has developed a draft specification 9809 for design and fabrication of high pressure cylinders with maximum tensile strength limitation of 1,100 N/mm{sup 2}. In order to extend the ISO 9809 rules for higher than 1,100 N/mm{sup 2} strength level cylinders, a working group WG14 was formed in 1989 to develop new rules to assure adequate fracture resistance. In 1994, WG14 recommended a simple, but unique flawed cylinder test method for design qualification of the cylinder and acceptance criteria to assure adequate fracture resistance. WG14 also recommended Charpy-V-Notch impact tests to control the required fracture resistance on production cylinders. This paper presents the technical basis that was employed in developing the flawed cylinder test method and acceptance criteria. The specification was developed for seamless steel cylinders having actual strength in the range of 1,100 to 1,400 N/mm{sup 2} and cylindrical section wall thickness in the range of 3mm to 10mm. Flawed cylinder tests were conducted on several hundred cylinders of varying sizes and strength levels. The specification requires to demonstrate LEAK-BEFORE-BREAK performance of the cylinder having flaw length equal to 1.6(O.D. {times} t{sub design}){sup 0.5} at failure pressure = (t{sub design}/t{sub actual}) {times} Design Pressure.

  7. Technical basis for flawed cylinder test specification to assure adequate fracture resistance of ISO high-strength steel cylinder

    SciTech Connect

    Rana, M.D.; Smith, J.H.; Tribolet, R.O.

    1997-11-01

    High-pressure industrial gases (such as oxygen, nitrogen, argon, hydrogen, etc.) are stored and transported in portable cylinders. ISO TC58 SC3 has developed a draft specification 9809 for design and fabrication of high-pressure cylinders with maximum tensile strength limitation of 1,100 N/mm{sup 2}. In order to extend the ISO 9809 rules for higher than 1,100 N/mm{sup 2} strength level cylinders, a working group WG14 was formed in 1989 to develop new rules to assure adequate fracture resistance. In 1994, WG14 recommended a simple, but unique flawed cylinder test method for design qualification of the cylinder and acceptance criteria to assure adequate fracture resistance. WG14 also recommended Charpy-V-notch impact tests to control the required fracture resistance on production cylinders. This paper presents the technical basis that was employed in developing the flawed cylinder test method and acceptance criteria. The specification was developed for seamless steel cylinders having actual strength in the range of 1,100 to 1,400 N/mm{sup 2} and cylindrical section wall thickness in the range of 3 to 10 mm. Flawed cylinder tests were conducted on several hundred cylinders of varying sizes and strength levels. The specification requires to demonstrate LEAK-BEFORE-BREAK performance of the cylinder having flaw length equal to 1.6 (o.d. {times} t{sub design}){sup 0.5} at failure pressure = (t{sub design}/t{sub actual}) x Design Pressure.

  8. GIS-modeling of an ice-dammed lake in the Lake Onega depression ca 14500-12500 Yrs BP

    NASA Astrophysics Data System (ADS)

    Subetto, Dmitry; Zobkov, Mikhail; Potakhin, Maksim; Tarasov, Aleksey

    2016-04-01

    Palaeogeographical reconstructions of the Onego ice-dammed lake development ca 14500-125000 yrs BP were based on the GIS approach. The palaeo-water-level surfaces were interpolated using a point-kriging approach. 14500-14000 Yrs BP: An ice-dammed lake occupied the southern part of the Lake Onega depression. The level of this lake was at 130-120 m a.s.l. and was controlled by a threshold of the water divide between the River Oshta and River Oyat', with discharge southwestward into the Oyat' basin. The surface area of the ice-dammed lake was 3500 sq.km. 14000-13300 Yrs BP: When the ice melted away from the mouth of the River Svir, the lake level dropped to 85-80 m a.s.l. and runoff was directed into the Lake Ladoga - easternmost part of The Baltic Ice Lake at that time. 13300-12500 Yrs BP: As the glacier retreated from the Lake Onega depression, the ice-dammed lake was occupied it and reached the maximum sizes (the surface area was 33000 sq.km). The new threshold in the northern part was opened and runoff was directed into the White Sea basin. During the conference new digital paleogeographical maps of the Onego ice-dammed lake will be presented. The study has been financially supported by the Russian Science Foundation (#14-17-00766).

  9. Solifluction activity in the present periglacial belt of Sierra Nevada during the last 8 ky BP

    NASA Astrophysics Data System (ADS)

    Oliva, M.; Schulte, L.; Gómez Ortiz, A.

    2009-04-01

    Solifluction records in Sierra Nevada (Andalusia, Spain) reveal a succession of environmental changes during the last millennia in this massif mostly related to Holocene climate dynamics. Geomorphological processes in Sierra Nevada react sensitively to small changes in temperature or moisture regimes, showing the proximity of these processes to their climate boundaries and the small climate range necessary to carry environmental changes in the summits of this massif. Solifluction dynamics in Sierra Nevada is influenced by a complex interaction between environmental factors (slope, vegetation cover, texture) and climate parameters (ground thermal regime, length and thickness of the snow cover, water supply). Interdependant feed-back mechanisms among all these variables make difficult to understand the key factors involved in present and past solifluction processes, although monitoring control performed on lobes with different emplacements suggest today's favourable environmental conditions for solifluction displacements. Water availability controls both vegetation cover and slope processes. In fact, currently water supply determines the grass cover in gentle valley floors, but it is also decisive to provide water for the small solifluction displacements detected during the monitored period. Thermal conditions also play a decisive role to activate solifluction or soil formation with similar moisture regimes. The very weak activity pattern of hundreds of solifluction lobes suggests that they must have developed in other more favourable climate conditions. We studied more than 30 sedimentological profiles from solifluction lobes in San Juan and Rio Seco valleys, which reveal an alternation of solifluction/edaphic cycles during the Holocene, with nine different geomorphic phases in the highest western cirques of Sierra Nevada. In San Juan valley, north exposed, there are several generations of solifluction lobes covering the last 8-9 ky BP, while in the southern Rio

  10. Effectiveness of blood pressure control outside the medical setting.

    PubMed

    Banegas, José R; Segura, Julián; Sobrino, Javier; Rodríguez-Artalejo, Fernando; de la Sierra, Alejandro; de la Cruz, Juan J; Gorostidi, Manuel; Sarría, Antonio; Ruilope, Luis M

    2007-01-01

    We studied the effectiveness of blood pressure (BP) control outside the clinic by using ambulatory BP monitoring (ABPM) among a large number of hypertensive subjects treated in primary care centers across Spain. The sample consisted of 12 897 treated hypertensive subjects who had indications for ABPM. Office-based BP was calculated as the average of 2 readings. Twenty-four-hour ABPM was then performed using a SpaceLabs 90207 monitor under standardized conditions. A total of 3047 patients (23.6%) had their office BP controlled, and 6657 (51.6%) were controlled according to daytime ABPM. The proportion of office resistance or underestimation of patients' BP control by physicians in the office (office BP >or=140/90 mm Hg and average daytime ambulatory BP <135/85 mm Hg) was 33.4%, and the proportion of isolated office control or overestimation of control (office BP <140/90 mm Hg and average daytime ambulatory BP >or=135/85 mm Hg) was 5.4%. BP control was more frequently underestimated in patients who were older, female, obese, or with morning BP determination than in their counterparts. BP control was more frequently overestimated in those who were younger, male, nonobese, smokers, or with evening BP determination. Ambulatory-based hypertension control was far better than office-based hypertension control. This conveys an encouraging message to clinicians, namely that they are actually doing better than is evidenced by office-based data. However, the burden of underestimation and overestimation of BP control at the office is still remarkable. Physicians should be aware that the likelihood of misestimating BP control is higher in some hypertensive subjects. PMID:17075026

  11. Modification over time of pulse wave velocity parallel to changes in aortic BP, as well as in 24-h ambulatory brachial BP.

    PubMed

    Oliveras, A; Segura, J; Suarez, C; García-Ortiz, L; Abad-Cardiel, M; Vigil, L; Gómez-Marcos, M A; Sans Atxer, L; Martell-Claros, N; Ruilope, L M; de la Sierra, A

    2016-03-01

    Arterial stiffness as assessed by carotid-femoral pulse wave velocity (cfPWV) is a marker of preclinical organ damage and a predictor of cardiovascular outcomes, independently of blood pressure (BP). However, limited evidence exists on the association between long-term variation (Δ) on aortic BP (aoBP) and ΔcfPWV. We aimed to evaluate the relationship of ΔBP with ΔcfPWV over time, as assessed by office and 24-h ambulatory peripheral BP, and aoBP. AoBP and cfPWV were evaluated in 209 hypertensive patients with either diabetes or metabolic syndrome by applanation tonometry (Sphygmocor) at baseline(b) and at 12 months of follow-up(fu). Peripheral BP was also determined by using validated oscillometric devices (office(o)-BP) and on an outpatient basis by using a validated (Spacelabs-90207) device (24-h ambulatory BP). ΔcfPWV over time was calculated as follows: ΔcfPWV=[(cfPWVfu-cfPWVb)/cfPWVb] × 100. ΔBP over time resulted from the same formula applied to BP values obtained with the three different measurement techniques. Correlations (Spearman 'Rho') between ΔBP and ΔcfPWV were calculated. Mean age was 62 years, 39% were female and 80% had type 2 diabetes. Baseline office brachial BP (mm Hg) was 143±20/82±12. Follow-up (12 months later) office brachial BP (mm Hg) was 136±20/79±12. ΔcfPWV correlated with ΔoSBP (Rho=0.212; P=0.002), Δ24-h SBP (Rho=0.254; P<0.001), Δdaytime SBP (Rho=0.232; P=0.001), Δnighttime SBP (Rho=0.320; P<0.001) and ΔaoSBP (Rho=0.320; P<0.001). A multiple linear regression analysis included the following independent variables: ΔoSBP, Δ24-h SBP, Δdaytime SBP, Δnighttime SBP and ΔaoSBP. ΔcfPWV was independently associated with Δ24-h SBP (β-coefficient=0.195; P=0.012) and ΔaoSBP (β-coefficient= 0.185; P=0.018). We conclude that changes in both 24-h SBP and aoSBP more accurately reflect changes in arterial stiffness than do office BP measurements. PMID:26108366

  12. Feasibility study report for the 200-BP-1 operable unit

    SciTech Connect

    Not Available

    1993-06-01

    This feasibility study examines a range of alternatives and provides recommendations for selecting a preferred alternative for remediating contamination at the 200-BP-1 operable unit. The 200-BP-1 operable unit is located in the center of the Hanford Site along the northern boundary of the 200 East Area. The 241-BY Tank Farm is located immediately to the south of the operable unit. 200-BP-1 is a source operable unit with contaminated soils associated primarily with nine inactive cribs (known as the 216-B cribs). These cribs were used for disposal of low-level radioactive liquid waste from U Plant uranium recovery operations, and waste storage tank condensate from the adjacent 241-BY Tank Farm. The cribs used for disposal of U Plant waste were in operation from 1955--1965, and the cribs used for disposal of tank condensate were in operation from 1965--1975. In addition to the cribs, four unplanned releases of radioactive materials have occurred within the operable unit. Contaminated surface soils associated with the unplanned releases have been consolidated over the cribs and covered with clean soil to reduce contaminant migration and exposure. Discharge of wastes to the cribs has resulted in soil and groundwater contamination. The groundwater is being addressed as part of the 200 East Aggregate Area, groundwater operable unit. Contaminated soils at the site can be categorized by the types of contaminants, their distribution in the soil column, and the risk posed by the various potential exposure pathways. Below the clean soil cover, the near surface soils contain low-levels of contamination with cesium-137, radium-226, strontium-90, thorium-228, and uranium. The lifetime incremental cancer risk associated with these soils if they were exposed at the surface is 9{times}10{sup {minus}5}.

  13. Dufulin Activates HrBP1 to Produce Antiviral Responses in Tobacco

    PubMed Central

    Chen, Zhuo; Zeng, Mengjiao; Song, Baoan; Hou, Chengrui; Hu, Deyu; Li, Xiangyang; Wang, Zhenchao; Fan, Huitao; Bi, Liang; Liu, Jiaju; Yu, Dandan; Jin, Linhong; Yang, Song

    2012-01-01

    Background Dufulin is a new antiviral agent that is highly effective against plant viruses and acts by activating systemic acquired resistance (SAR) in plants. In recent years, it has been used widely to prevent and control tobacco and rice viral diseases in China. However, its targets and mechanism of action are still poorly understood. Methodology/Principal Findings Here, differential in-gel electrophoresis (DIGE) and classical two-dimensional electrophoresis (2-DE) techniques were combined with mass spectrometry (MS) to identify the target of Dufulin. More than 40 proteins were found to be differentially expressed (≥1.5 fold or ≤1.5 fold) upon Dufulin treatment in Nicotiana tabacum K326. Based on annotations in the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, these proteins were found to be related to disease resistance. Directed acyclic graph (DAG) analysis of the various pathways demonstrated harpin binding protein-1 (HrBP1) as the target of action of Dufulin. Additionally, western blotting, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and real time PCR analyses were also conducted to identify the specific mechanism of action of Dufulin. Our results show that activation of HrBP1 triggers the salicylic acid (SA) signaling pathway and thereby produces antiviral responses in the plant host. A protective assay based on lesion counting further confirmed the antiviral activity of Dufulin. Conclusion This study identified HrBP1 as a target protein of Dufulin and that Dufulin can activate the SA signaling pathway to induce host plants to generate antiviral responses. PMID:22662252

  14. Heritability of HR and BP Response To Exercise Training in the HERITAGE Family Study.

    ERIC Educational Resources Information Center

    Rice, Treva; Gagnon, Jacques; Leon, Arthur S.; Skinner, James S.; Wilmore, Jack H.; Bouchard, Claude; Rao, D. C.

    2002-01-01

    Assessed the heritability of response to exercise training in resting blood pressure (BP) and heart rate (HR) among sedentary Caucasians comprising 98 families who completed an exercise training program. Results indicated that the trainability of systolic BP and HR in families with elevated BP was partially determined by genetic factors. Diastolic…

  15. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

    SciTech Connect

    Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.

    2015-04-15

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

  16. Risk assessment of logistics outsourcing based on BP neural network

    NASA Astrophysics Data System (ADS)

    Liu, Xiaofeng; Tian, Zi-you

    The purpose of this article is to evaluate the risk of the enterprises logistics outsourcing. To get this goal, the paper first analysed he main risks existing in the logistics outsourcing, and then set up a risk evaluation index system of the logistics outsourcing; second applied BP neural network into the logistics outsourcing risk evaluation and used MATLAB to the simulation. It proved that the network error is small and has strong practicability. And this method can be used by enterprises to evaluate the risks of logistics outsourcing.

  17. Systolic BP and Mortality in Older Adults with CKD

    PubMed Central

    Peters, Dawn; Yang, Xiuhai; Petrik, Amanda; Smith, David H.; Johnson, Eric S.; Thorp, Micah L.; Morris, Cynthia; O’Hare, Ann M.

    2015-01-01

    Background and objectives Optimal BP targets for older adults with CKD are unclear. This study sought to determine whether a nonlinear relationship between BP and mortality—as described for the broader CKD population and for older adults in the general population—is present for older adults with CKD. Design, setting, participants, & measurements A cohort of 21,015 adults age 65–105 years with a moderate or severe reduction in eGFR (<60 ml/min per 1.73 m2) were identified within the Kaiser Permanente Northwest Health Maintenance Organization population. The relationship between baseline systolic BP (SBP; ≤120, 121–130, 131–140, 141–150, >150 mmHg; referent, 131–140 mmHg) and all-cause mortality across age groups (65–70, 71–80, and >80 years) was examined; patients were followed for up to 11 years after cohort entry. Results The median times at risk were 3.15 years, 3.53 years, and 2.76 years for adults age 65–70, 71–80, and >80 years, respectively. Mortality during follow-up was 19.6% for those age 65–70 years, 33.4% for those age 71–80 years, and 55.7% for those age >80 years. The relationship between SBP and mortality varied as a function of age. The risk of death was highest for patients with the lowest SBP in all age groups. Only among adults age 65–70 years was an SBP>140 mmHg associated with a higher risk of death compared with the referent category. Patterns of age modification of the relationship between SBP and mortality were consistent in all sensitivity analyses. Conclusions In a cohort of older adults, the relationship between SBP and mortality varied systematically with age. A relationship between higher SBP and mortality was present only for younger members of this cohort and not for those older than 70. These results raise the question of whether the relative benefits and harms of lowering BP to recommended targets for older adults with CKD may vary as a function of age. PMID:26276142

  18. Complement regulator C4BP binds to Staphylococcus aureus surface proteins SdrE and Bbp inhibiting bacterial opsonization and killing☆

    PubMed Central

    Hair, Pamela S.; Foley, Caitlin K.; Krishna, Neel K.; Nyalwidhe, Julius O.; Geoghegan, Joan A.; Foster, Timothy J.; Cunnion, Kenji M.

    2013-01-01

    Staphylococcus aureus is a premier human pathogen and the most common cause of osteoarticular, wound, and implanted device infections. We recently demonstrated S. aureus efficiently binds the classical complement regulator C4b-binding protein (C4BP) inhibiting antibody-initiated complement-mediated opsonization. Here we identify S. aureus surface protein SdrE as a C4BP-binding protein. Recombinant SdrE and recombinant bone sialoprotein-binding protein (Bbp), an allelic variant of SdrE, both efficiently bound to C4BP in heat-inactivated human serum. We previously described SdrE as binding alternative pathway regulator factor H. Recombinant SdrE and Bbp efficiently bound C4BP and factor H in serum without apparent interference. Gain of function studies utilizing Lactococcus lactis clones expressing SdrE or Bbp increased serum C4BP and factor H binding, compared with empty-vector control (WT) approximately 2-fold. Correspondingly, classical pathway-mediated C3-fragment opsonization and bacterial killing by human neutrophils decreased by half for L. lactis clones expressing SdrE or Bbp compared with WT. In summary, we identify SdrE and allelic variant Bbp as S. aureus surface proteins that bind the complement regulator C4BP inhibiting classical pathway-mediated bacterial opsonization and killing. PMID:24600566

  19. Axial 3D region of interest reconstruction using weighted cone beam BPF/DBPF algorithm cascaded with adequately oriented orthogonal butterfly filtering

    NASA Astrophysics Data System (ADS)

    Tang, Shaojie; Tang, Xiangyang

    2016-03-01

    Axial cone beam (CB) computed tomography (CT) reconstruction is still the most desirable in clinical applications. As the potential candidates with analytic form for the task, the back projection-filtration (BPF) and the derivative backprojection filtered (DBPF) algorithms, in which Hilbert filtering is the common algorithmic feature, are originally derived for exact helical and axial reconstruction from CB and fan beam projection data, respectively. These two algorithms have been heuristically extended for axial CB reconstruction via adoption of virtual PI-line segments. Unfortunately, however, streak artifacts are induced along the Hilbert filtering direction, since these algorithms are no longer accurate on the virtual PI-line segments. We have proposed to cascade the extended BPF/DBPF algorithm with orthogonal butterfly filtering for image reconstruction (namely axial CB-BPP/DBPF cascaded with orthogonal butterfly filtering), in which the orientation-specific artifacts caused by post-BP Hilbert transform can be eliminated, at a possible expense of losing the BPF/DBPF's capability of dealing with projection data truncation. Our preliminary results have shown that this is not the case in practice. Hence, in this work, we carry out an algorithmic analysis and experimental study to investigate the performance of the axial CB-BPP/DBPF cascaded with adequately oriented orthogonal butterfly filtering for three-dimensional (3D) reconstruction in region of interest (ROI).

  20. Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

    SciTech Connect

    J Wingard; J Ladner; M Vanarotti; A Fisher; H Robinson; K Buchanan; D Engman; J Ames

    2011-12-31

    The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically with flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..

  1. Adequate bases of phase space master integrals for gg → h at NNLO and beyond

    NASA Astrophysics Data System (ADS)

    Höschele, Maik; Hoff, Jens; Ueda, Takahiro

    2014-09-01

    We study master integrals needed to compute the Higgs boson production cross section via gluon fusion in the infinite top quark mass limit, using a canonical form of differential equations for master integrals, recently identified by Henn, which makes their solution possible in a straightforward algebraic way. We apply the known criteria to derive such a suitable basis for all the phase space master integrals in afore mentioned process at next-to-next-to-leading order in QCD and demonstrate that the method is applicable to next-to-next-to-next-to-leading order as well by solving a non-planar topology. Furthermore, we discuss in great detail how to find an adequate basis using practical examples. Special emphasis is devoted to master integrals which are coupled by their differential equations.

  2. Dietary intake of nutrients with adequate intake values in the dietary reference intakes for Japanese.

    PubMed

    Tsuboyama-Kasaoka, Nobuyo; Takizawa, Asuka; Tsubota-Utsugi, Megumi; Nakade, Makiko; Imai, Eri; Kondo, Akiko; Yoshida, Kazue; Okuda, Nagako; Nishi, Nobuo; Takimoto, Hidemi

    2013-01-01

    The Adequate Intake (AI) values in the Dietary Reference Intakes for Japanese (DRIs-J) 2010 were mainly determined based on the median intakes from 2 y of pooled data (2005-2006) from the National Health and Nutrition Survey-Japan (NHNS-J). However, it remains unclear whether 2 y of pooled data from the NHNS-J are appropriate for evaluating the intake of the population. To clarify the differences in nutrient intakes determined from 2 and 7 y of pooled data, we analyzed selected nutrient intake levels by sex and age groups using NHNS-J data. Intake data were obtained from 64,624 individuals (age: ≥1 y; 47.4% men) who completed a semi-weighed 1-d household dietary record that was part of the NHNS-J conducted annually in Japan from 2003 to 2009. There were no large differences between the median intakes calculated from 2 or 7 y of pooled data for n-6 or n-3 polyunsaturated fatty acids (PUFAs), vitamin D, pantothenic acid, potassium, or phosphorus. When the AI values and median intakes were compared, there was no large difference in the values for n-6 or n-3 PUFAs, pantothenic acid, or phosphorus. Conversely, the AI values for vitamin D and potassium differed from the median intakes of these nutrients for specific sex and age groups, because values were not based on NHNS-J data. Our results indicate that 2 y of pooled data from the NHNS-J adequately reflect the population's intake, and that the current system for determination of AI values will be applicable for future revisions.

  3. Intersection of race/ethnicity and gender in depression care: screening, access, and minimally adequate treatment

    PubMed Central

    Hahm, Hyeouk Chris; Cook, Benjamin; Ault-Brutus, Andrea; Alegria, Margarita

    2015-01-01

    Objectives This study was conducted to understand the interaction of race/ethnicity and gender in depression screening, any mental health care, and adequate care. Methods 2010–2012 electronic health records data of adult primary care patients from a New England urban health care system was used (n = 65,079). Multivariate logit regression models were used to assess the associations between race/ethnicity, gender, and other covariates with depression screening, any depression care among those screened positive, and adequate depression care among users. Secondly, disparities were evaluated by race/ethnicity and gender and incorporated differences due to insurance, marital status, and area-level SES measures. Findings Black and Asian males and females were less likely to be screened for depression compared to their white counterparts, while Latino males and females were more likely to be screened. Among those that screened PHQ-9>10, black males and females, Latino males, and Asian males and females were less likely to receive any mental health care than their white counterparts. The black-white disparity in screening was greater for females compared to males. The Latino-white disparity for any mental health care and adequacy of care was greater for males compared to females. Conclusions Our approach underscores the importance of identifying disparities at each step of depression care by both race/ethnicity and gender. Targeting certain groups in specific stages of care would be more effective (i.e., screening of black females, any mental health care and adequacy of care for Latino males) than a blanket approach to disparities reduction. PMID:25727113

  4. Are the Psychological Needs of Adolescent Survivors of Pediatric Cancer Adequately Identified and Treated?

    PubMed Central

    Kahalley, Lisa S.; Wilson, Stephanie J.; Tyc, Vida L.; Conklin, Heather M.; Hudson, Melissa M.; Wu, Shengjie; Xiong, Xiaoping; Stancel, Heather H.; Hinds, Pamela S.

    2012-01-01

    Objectives To describe the psychological needs of adolescent survivors of acute lymphoblastic leukemia (ALL) or brain tumor (BT), we examined: (a) the occurrence of cognitive, behavioral, and emotional concerns identified during a comprehensive psychological evaluation, and (b) the frequency of referrals for psychological follow-up services to address identified concerns. Methods Psychological concerns were identified on measures according to predetermined criteria for 100 adolescent survivors. Referrals for psychological follow-up services were made for concerns previously unidentified in formal assessment or not adequately addressed by current services. Results Most survivors (82%) exhibited at least one concern across domains: behavioral (76%), cognitive (47%), and emotional (19%). Behavioral concerns emerged most often on scales associated with executive dysfunction, inattention, learning, and peer difficulties. CRT was associated with cognitive concerns, χ2(1,N=100)=5.63, p<0.05. Lower income was associated with more cognitive concerns for ALL survivors, t(47)=3.28, p<0.01, and more behavioral concerns for BT survivors, t(48)=2.93, p<0.01. Of survivors with concerns, 38% were referred for psychological follow-up services. Lower-income ALL survivors received more referrals for follow-up, χ2(1,N=41)=8.05, p<0.01. Referred survivors had more concerns across domains than non-referred survivors, ALL: t(39)=2.96, p<0.01, BT: t(39)=3.52, p<0.01. Trends suggest ALL survivors may be at risk for experiencing unaddressed cognitive needs. Conclusions Many adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long-term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors’ needs, particularly for lower-income survivors and those treated with CRT. PMID:22278930

  5. Use of Linear Programming to Develop Cost-Minimized Nutritionally Adequate Health Promoting Food Baskets

    PubMed Central

    Tetens, Inge; Dejgård Jensen, Jørgen; Smed, Sinne; Gabrijelčič Blenkuš, Mojca; Rayner, Mike; Darmon, Nicole; Robertson, Aileen

    2016-01-01

    Background Food-Based Dietary Guidelines (FBDGs) are developed to promote healthier eating patterns, but increasing food prices may make healthy eating less affordable. The aim of this study was to design a range of cost-minimized nutritionally adequate health-promoting food baskets (FBs) that help prevent both micronutrient inadequacy and diet-related non-communicable diseases at lowest cost. Methods Average prices for 312 foods were collected within the Greater Copenhagen area. The cost and nutrient content of five different cost-minimized FBs for a family of four were calculated per day using linear programming. The FBs were defined using five different constraints: cultural acceptability (CA), or dietary guidelines (DG), or nutrient recommendations (N), or cultural acceptability and nutrient recommendations (CAN), or dietary guidelines and nutrient recommendations (DGN). The variety and number of foods in each of the resulting five baskets was increased through limiting the relative share of individual foods. Results The one-day version of N contained only 12 foods at the minimum cost of DKK 27 (€ 3.6). The CA, DG, and DGN were about twice of this and the CAN cost ~DKK 81 (€ 10.8). The baskets with the greater variety of foods contained from 70 (CAN) to 134 (DGN) foods and cost between DKK 60 (€ 8.1, N) and DKK 125 (€ 16.8, DGN). Ensuring that the food baskets cover both dietary guidelines and nutrient recommendations doubled the cost while cultural acceptability (CAN) tripled it. Conclusion Use of linear programming facilitates the generation of low-cost food baskets that are nutritionally adequate, health promoting, and culturally acceptable. PMID:27760131

  6. 21 CFR 740.10 - Labeling of cosmetic products for which adequate substantiation of safety has not been obtained.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Labeling of cosmetic products for which adequate..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS COSMETIC PRODUCT WARNING STATEMENTS Warning Statements § 740.10 Labeling of cosmetic products for which adequate substantiation of safety has not...

  7. 21 CFR 740.10 - Labeling of cosmetic products for which adequate substantiation of safety has not been obtained.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Labeling of cosmetic products for which adequate..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS COSMETIC PRODUCT WARNING STATEMENTS Warning Statements § 740.10 Labeling of cosmetic products for which adequate substantiation of safety has not...

  8. 21 CFR 740.10 - Labeling of cosmetic products for which adequate substantiation of safety has not been obtained.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Labeling of cosmetic products for which adequate..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS COSMETIC PRODUCT WARNING STATEMENTS Warning Statements § 740.10 Labeling of cosmetic products for which adequate substantiation of safety has not...

  9. 21 CFR 740.10 - Labeling of cosmetic products for which adequate substantiation of safety has not been obtained.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Labeling of cosmetic products for which adequate..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS COSMETIC PRODUCT WARNING STATEMENTS Warning Statements § 740.10 Labeling of cosmetic products for which adequate substantiation of safety has not...

  10. 21 CFR 740.10 - Labeling of cosmetic products for which adequate substantiation of safety has not been obtained.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Labeling of cosmetic products for which adequate..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) COSMETICS COSMETIC PRODUCT WARNING STATEMENTS Warning Statements § 740.10 Labeling of cosmetic products for which adequate substantiation of safety has not...

  11. Chronic Alcohol Exposure Decreases 53BP1 Protein Levels Leading to a Defective DNA Repair in Cultured Primary Cortical Neurons.

    PubMed

    Romero, Ana M; Palanca, Ana; Ruiz-Soto, Maria; Llorca, Javier; Marín, María P; Renau-Piqueras, Jaime; Berciano, Maria T; Lafarga, Miguel

    2016-01-01

    Chronic alcohol consumption may cause neurodevelopmental and neurodegenerative disorders. Alcohol neurotoxicity is associated with the production of acetaldehyde and reactive oxygen species that induce oxidative DNA damage. However, the molecular mechanisms by which ethanol disturbs the DNA damage response (DDR), resulting in a defective DNA repair, remain unknown. Here, we have used cultured primary cortical neurons exposed to 50 or 100 mM ethanol for 7 days to analyze the ethanol-induced DDR. Ethanol exposure produced a dose-dependent generation of double strand breaks and the formation of DNA damage foci immunoreactive for the histone γH2AX, a DNA damage marker, and for the ubiquitylated H2A, which is involved in chromatin remodeling at DNA damage sites. Importantly, these DNA damage foci failed to recruit the protein 53BP1, a crucial DNA repair factor. This effect was associated with a drop in 53BP1 mRNA and protein levels and with an inhibition of global transcription. Moreover, ethanol-exposed neurons treated with ionizing radiation (2 Gy) also failed to recruit 53BP1 at DNA damage foci and exhibited a greater vulnerability to DNA lesions than irradiated control neurons. Our results support that defective DNA repair, mediated by the deficient expression and recruitment of 53BP1 to DNA damage sites, represents a novel mechanism involved in ethanol neurotoxicity. The design of therapeutic strategies that increase or stabilize 53BP1 levels might potentially promote DNA repair and partially compensate alcohol neurotoxicity.

  12. SPECTROPOLARIMETRY OF THE CLASSICAL T TAURI STAR BP TAU

    SciTech Connect

    Chen, Wei; Johns-Krull, Christopher M. E-mail: cmj@rice.edu

    2013-10-20

    We implement a least-squares deconvolution (LSD) code to study magnetic fields on cool stars. We first apply our code to high-resolution optical echelle spectra of 53 Cam (a magnetic Ap star) and three well-studied cool stars (Arcturus, 61 Cyg A, and ξ Boo A) as well as the Sun (by observing the asteroid Vesta) as tests of the code and the instrumentation. Our analysis is based on several hundred photospheric lines spanning the wavelength range 5000 Å to 9000 Å. We then apply our LSD code to six nights of data on the Classical T Tauri Star BP Tau. A maximum longitudinal field of 370 ± 80 G is detected from the photospheric lines on BP Tau. A 1.8 kG dipole tilted at 129° with respect to the rotation axis and a 1.4 kG octupole tilted at 104° with respect to the rotation axis, both with a filling factor of 0.25, best fit our LSD Stokes V profiles. Measurements of several emission lines (He I 5876 Å, Ca II 8498 Å, and 8542 Å) show the presence of strong magnetic fields in the line formation regions of these lines, which are believed to be the base of the accretion footpoints. The field strength measured from these lines shows night-to-night variability consistent with rotation of the star.

  13. Redetermination of Fe(2)[BP(3)O(12)].

    PubMed

    Li, Fei Fei; Zhang, Hui Ju; Zhang, Li Na

    2010-01-01

    Explorations of phases in the quaternary Fe(III)-B(III)-P(V)-O system prepared by the high temperature solution growth (HTSG) method led to single-crystal growth of anhydrous diiron(III) borotriphosphate, Fe(2)[BP(3)O(12)]. This phase has been synthesized previously as a microcrystalline material and its structure refined in space group P3 from powder X-ray diffraction data using the Rietveld method [Chen et al. (2004 ▶). J. Inorg. Mater.19, 429-432]. In the current single-crystal study, it was shown that the correct space group is P6(3)/m. The three-dimensional structure of the title compound is built up from FeO(6) octa-hedra (3.. symmetry), trigonal-planar BO(3) groups ( symmetry) and PO(4) tetra-hedra (m.. symmetry). Two FeO(6) octa-hedra form Fe(2)O(9) dimers via face-sharing, while the anionic BO(3) and PO(4) groups are connected via corner-sharing to build up the [BP(3)O(12)](6-) anion. Both units are inter-connected via corner-sharing.

  14. Spectropolarimetry of the Classical T Tauri Star BP Tau

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Johns-Krull, Christopher M.

    2013-10-01

    We implement a least-squares deconvolution (LSD) code to study magnetic fields on cool stars. We first apply our code to high-resolution optical echelle spectra of 53 Cam (a magnetic Ap star) and three well-studied cool stars (Arcturus, 61 Cyg A, and ξ Boo A) as well as the Sun (by observing the asteroid Vesta) as tests of the code and the instrumentation. Our analysis is based on several hundred photospheric lines spanning the wavelength range 5000 Å to 9000 Å. We then apply our LSD code to six nights of data on the Classical T Tauri Star BP Tau. A maximum longitudinal field of 370 ± 80 G is detected from the photospheric lines on BP Tau. A 1.8 kG dipole tilted at 129° with respect to the rotation axis and a 1.4 kG octupole tilted at 104° with respect to the rotation axis, both with a filling factor of 0.25, best fit our LSD Stokes V profiles. Measurements of several emission lines (He I 5876 Å, Ca II 8498 Å, and 8542 Å) show the presence of strong magnetic fields in the line formation regions of these lines, which are believed to be the base of the accretion footpoints. The field strength measured from these lines shows night-to-night variability consistent with rotation of the star.

  15. Expression and Localization of CaBP Ca2+ Binding Proteins in the Mouse Cochlea.

    PubMed

    Yang, Tian; Scholl, Elizabeth S; Pan, Ning; Fritzsch, Bernd; Haeseleer, Françoise; Lee, Amy

    2016-01-01

    CaBPs are a family of EF-hand Ca2+ binding proteins that are structurally similar to calmodulin. CaBPs can interact with, and yet differentially modulate, effectors that are regulated by calmodulin, such as Cav1 voltage-gated Ca2+ channels. Immunolabeling studies suggest that multiple CaBP family members (CaBP1, 2, 4, and 5) are expressed in the cochlea. To gain insights into the respective auditory functions of these CaBPs, we characterized the expression and cellular localization of CaBPs in the mouse cochlea. By quantitative reverse transcription PCR, we show that CaBP1 and CaBP2 are the major CaBPs expressed in mouse cochlea both before and after hearing onset. Of the three alternatively spliced variants of CaBP1 (caldendrin, CaBP1-L, and CaBP1-S) and CaBP2 (CaBP2-alt, CaBP2-L, CaBP2-S), caldendrin and CaBP2-alt are the most abundant. By in situ hybridization, probes recognizing caldendrin strongly label the spiral ganglion, while probes designed to recognize all three isoforms of CaBP1 weakly label both the inner and outer hair cells as well as the spiral ganglion. Within the spiral ganglion, caldendrin/CaBP1 labeling is associated with cells resembling satellite glial cells. CaBP2-alt is strongly expressed in inner hair cells both before and after hearing onset. Probes designed to recognize all three variants of CaBP2 strongly label inner hair cells before hearing onset and outer hair cells after the onset of hearing. Thus, CaBP1 and CaBP2 may have overlapping roles in regulating Ca2+ signaling in the hair cells, and CaBP1 may have an additional function in the spiral ganglion. Our findings provide a framework for understanding the role of CaBP family members in the auditory periphery. PMID:26809054

  16. The Role of Home Blood Pressure Telemonitoring for Blood Pressure Control

    PubMed Central

    Lee, Chan Joo; Park, Sungha

    2016-01-01

    Despite improvements in hypertension awareness and treatment, the blood pressure (BP) control rate still remains at around 50%. One of the major determinants of low BP control results from therapeutic inertia of the physician and suboptimal compliance of the patients. Home BP self-measurement and monitoring improves patients' awareness and helps the management of hypertension. Recent technological advances are allowing for accurate measurement and telemonitoring of home BP, with a number of randomized clinical trials demonstrating the efficacy of telemonitoring for BP control. Home BP telemonitoring combined with self-adjustment based on prespecified treatment algorithms has been shown to improve BP control. Additionally, telemonitoring with active intervention by medical professionals has been shown to improve drug compliance and increase the target BP achievement rate. Although nothing can replace the tried and tested doctor-patient relationship in the office, telemonitoring of home BP will be an important tool for treating hypertension in the future. PMID:27752479

  17. Quantitative contributions of CtBP-dependent and -independent repression activities of Knirps.

    PubMed

    Struffi, Paolo; Corado, Maria; Kulkarni, Meghana; Arnosti, David N

    2004-05-01

    The Drosophila Knirps protein is a short-range transcriptional repressor that locally inhibits activators by recruiting the CtBP co-repressor. Knirps also possesses CtBP-independent repression activity. The functional importance of multiple repression activities is not well understood, but the finding that Knirps does not repress some cis-regulatory elements in the absence of CtBP suggested that the co-factor may supply a unique function essential to repress certain types of activators. We assayed CtBP-dependent and -independent repression domains of Knirps in Drosophila embryos, and found that the CtBP-independent activity, when provided at higher than normal levels, can repress an eve regulatory element that normally requires CtBP. Dose response analysis revealed that the activity of Knirps containing both CtBP-dependent and -independent repression activities is higher than that of the CtBP-independent domain alone. The requirement for CtBP at certain enhancers appears to reflect the need for overall higher levels of repression, rather than a requirement for an activity unique to CtBP. Thus, CtBP contributes quantitatively, rather than qualitatively, to overall repression function. The finding that both repression activities are simultaneously deployed suggests that the multiple repression activities do not function as cryptic 'backup' systems, but that each contributes quantitatively to total repressor output.

  18. A Structure-Adaptive Hybrid RBF-BP Classifier with an Optimized Learning Strategy

    PubMed Central

    Wen, Hui; Xie, Weixin; Pei, Jihong

    2016-01-01

    This paper presents a structure-adaptive hybrid RBF-BP (SAHRBF-BP) classifier with an optimized learning strategy. SAHRBF-BP is composed of a structure-adaptive RBF network and a BP network of cascade, where the number of RBF hidden nodes is adjusted adaptively according to the distribution of sample space, the adaptive RBF network is used for nonlinear kernel mapping and the BP network is used for nonlinear classification. The optimized learning strategy is as follows: firstly, a potential function is introduced into training sample space to adaptively determine the number of initial RBF hidden nodes and node parameters, and a form of heterogeneous samples repulsive force is designed to further optimize each generated RBF hidden node parameters, the optimized structure-adaptive RBF network is used for adaptively nonlinear mapping the sample space; then, according to the number of adaptively generated RBF hidden nodes, the number of subsequent BP input nodes can be determined, and the overall SAHRBF-BP classifier is built up; finally, different training sample sets are used to train the BP network parameters in SAHRBF-BP. Compared with other algorithms applied to different data sets, experiments show the superiority of SAHRBF-BP. Especially on most low dimensional and large number of data sets, the classification performance of SAHRBF-BP outperforms other training SLFNs algorithms. PMID:27792737

  19. [Is blood pressure control different in women than in men?].

    PubMed

    Oliveras, A; Sans-Atxer, L; Vázquez, S

    2015-01-01

    Blood pressure (BP) evolves with age; until the 50's it is higher in men than in women, equaling and even then increasing in women. The prevalence of controlled BP appears to be similar between the sexes, but the prevalence of cardiovascular disease is higher in women than in men. The possibility that BP influences the cardiovascular risk differently according to sex must therefore be considered. While some studies suggest no difference exists, others have shown evidence of an increased risk in women with respect to men despite equal BP. In this way, it seems that the measurement of ambulatory BP, but not office BP, would mark the differences in the association between BP-gender and cardiovascular risk. It should therefore be investigated the possibility of a different BP goal for women and men, especially by evaluating ambulatory BP.

  20. [Is blood pressure control different in women than in men?].

    PubMed

    Oliveras, A; Sans-Atxer, L; Vázquez, S

    2015-01-01

    Blood pressure (BP) evolves with age; until the 50's it is higher in men than in women, equaling and even then increasing in women. The prevalence of controlled BP appears to be similar between the sexes, but the prevalence of cardiovascular disease is higher in women than in men. The possibility that BP influences the cardiovascular risk differently according to sex must therefore be considered. While some studies suggest no difference exists, others have shown evidence of an increased risk in women with respect to men despite equal BP. In this way, it seems that the measurement of ambulatory BP, but not office BP, would mark the differences in the association between BP-gender and cardiovascular risk. It should therefore be investigated the possibility of a different BP goal for women and men, especially by evaluating ambulatory BP. PMID:26486463

  1. IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

    PubMed

    Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

    2016-05-31

    Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. PMID:27210763

  2. IGF2BP3 modulates the interaction of invasion-associated transcripts with RISC

    PubMed Central

    Ennajdaoui, Hanane; Howard, Jonathan M.; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J.; Uren, Philip J.; Dargyte, Marija; Katzman, Sol; Draper, Jolene M.; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C.; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D.; Toloue, Masoud M.; Blencowe, Benjamin J.; Penalva, Luiz O.F.; Sanford, Jeremy R.

    2016-01-01

    Summary Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy. But its role(s) in pathogenesis remain enigmatic. Here, we interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches we identify 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and miRNA binding sites. IGF2BP3 promotes association of the RNA induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. PMID:27210763

  3. Impact of GNB3-C825T, ADRB3-Trp64Arg, UCP2-3′UTR 45 bp del/ins, and PPARγ-Pro12Ala Polymorphisms on Bofutsushosan Response in Obese Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Park, Junghyun; Bose, Shambhunath; Hong, Sun-Woo; Lee, Dong-Ki; Yoo, Jae-Wook; Lim, Chi-Yeon; Lee, Myeongjong

    2014-01-01

    Abstract Obesity is known to be influenced by a number of genes, including the β3 subunit of G protein (GNB3), β3-adrenergic receptor (ADRB3), uncoupling protein 2 (UCP2), and peroxisome proliferator activated receptor gamma (PPARγ). The single nucleotide polymorphisms (SNPs) of the above genes, such as GNB3-C825T, ADRB3-Trp64Arg, UCP2-3′UTR 45 bp del/ins, and PPARγ-Pro12Ala, are associated with obesity and body mass index. The present study evaluates the impact of Bofutsushosan, a traditional Eastern Asian herbal medicine with known anti-obesity properties, on obese subjects according to the presence of the above-mentioned SNPs. Upon randomization, the volunteers were allocated to receive Bofutsushosan (n=55) or placebo (n=56) treatments for 8 weeks. Following the treatment schedule, significant reductions in total cholesterol and significant improvement in the Korean version of obesity-related quality of life scale were seen in the Bofutsushosan-treated group, but not in placebo. Bofutsushosan exerted significant anti-obesity effects on a number of parameters in the carriers of the GNB3-825T allele, but only on waist circumference in the GNB3-C/C homozygote. Significant anti-obesity impact of Bofutsushosan was also seen on a number of obesity-indices in both ADRB3-Arg64 carriers and ADRB3-Trp64 homozygotes, as well as in UCP2-D/D carriers, but not in UCP2-D/I+I/I variants. The effect of Bofutsushosan was more pronounced in PPARγ-Pro/Pro genotype compared to PPARγ-Pro/Ala variants. Thus, the results revealed differential responses of the subjects to the anti-obesity effects of Bofutsushosan treatment according to the polymorphism of the vital obesity-related genes. Our study provides new insight into individualized clinical applications of Bofutsushosan for obesity. PMID:24827746

  4. An Analysis of the Rapidly Rotating Bp star HD 133880

    NASA Technical Reports Server (NTRS)

    Bailey, J. D.; Grunhut, J.; Shultz, M.; Wade, G.; Landstreet, J. D.; Bohlender, D.; Lim, J.; Wong, K.; Drake, S.; Linsky, J.

    2012-01-01

    HD 133880 is a rapidly rotating chemically peculiar B-type (Bp) star (nu sin i approx = 103km/s) and is host to one of the strongest magnetic fields of any Ap/Bp star. A member of the Upper Centaurus Lupus association, it is a star with a well-determined age of 16 Myr. 12 new spectra, four of which are polarimetric, obtained from the FEROS, ESPaDOnS and HARPS instruments, provide sufficient material from which to re-evaluate the magnetic field and obtain a first approximation to the atmospheric abundance distributions of He, O, Mg, Si, Ti. Cr, Fe, Ni, Pr and Nd. An abundance analysis was carried out using ZEEMAN, a program which synthesizes spectral line profiles for stars with permeating magnetic fields. The magnetic field structure was characterized by a colinear multipole expansion from the observed variations of the longitudinal and surface fields with rotational phase. Both magnetic hemispheres are clearly visible during the stellar rotation, and thus a three-ring abundance distribution model encompassing both magnetic poles and magnetic equator with equal spans in colatitude was adopted. Using the new magnetic field measurements and optical photometry together with previously published data, we refine the period of HD 133880 to P = 0.877 476 +/- 0.000009 d. Our simple axisymmetric magnetic field model is based on a predominantly quadrupolar component that roughly describes the field variations. Using spectrum synthesis, we derived mean abundances for O, Mg, Si, Ti, Cr, Fe and Pr. All elements; except Mg, are overabundant compared to the Son. Mg appears to be approximately uniform over the stellar surface, while all other elements are more abundant in the negative magnetic hemisphere than in the positive magnetic hemisphere. In contrast to most Ap/Bp stars which show an underabundance in 0, in HD 133880 this element is clearly overabundant compared to the solar abundance ratio. In studying the Ha and Paschen lines in the optical spectra, we could not

  5. The utilization of orbital images as an adequate form of control of preserved areas. [Araguaia National Park, Brazil

    NASA Technical Reports Server (NTRS)

    Dejesusparada, N. (Principal Investigator); Dossantos, J. R.

    1981-01-01

    The synoptic view and the repetitive acquisition of LANDSAT imagery provide precise information, in real-time, for monitoring preserved areas based on spectral, temporal and spatial properties. The purpose of this study was to monitor, with the use of multispectral imagery, the systematic annual burning, which causes the degradation of ecosystems in the National Park of Araguaia. LANDSAT imagery of channel 5 (0.6 a 0.7 microns) and 7 (0.8 a 1.1 microns), at the scale of 1:250.000, were used to identify and delimit vegetation units and burned area, based on photointerpretation parameter of tonality. The results show that the gallery forest can be discriminated from the seasonally flooded 'campo cerrado', and that 4,14% of the study area was burned. Conclusions point out that the LANDSAT images can be used for the implementation of environmental protection in national parks.

  6. Extracorporeal Shockwave Lithotripsy Monotherapy is not Adequate for Management of Staghorn Renal Calculi.

    PubMed

    Koko, Abdelmoniem K; Onuora, Vincent C; Al Turki, Mohammed A; Mesbed, Ahmed H; Al Jawini, Nasser A

    2003-01-01

    Between 1990 and 1999 a total of 186 patients with staghorn renal stones were treated in our unit. Of them, 76 patients were managed by extra-corporeal shockwave lithotripsy (ESWL) alone using a third generation Siemen's Lithostar Plus lithotriptor. Sixty-one of these patients who completed a follow-up of 41 months formed the subjects of this study. ESWL was done after routine stenting of the affected side in all cases except one. The mean number of ESWL sessions was 5.2, delivering an average 15,940 shocks per patient. The average hospital stay was 21.68 days and the duration of the treatment was 1-41 months (mean 6.75 months). Significant complications occurred in 35 patients (57.4%) eight of whom sustained multiple significant complications. A total of 162 auxiliary procedures were used in conjunction with ESWL and in the management of complications. The stone free rate at three months was 18%, but rose by the end of the treatment period (41 months) to 63.9%. Our study indicates that ESWL monotherapy is associated with high morbidity rates, high rates of unplanned invasive procedures as well as prolonged treatment periods and hospitalization. Thus, ESWL monotherapy is not adequate for the management of staghorn calculi.

  7. Cardiac catecholamines in rats fed copper deficient or copper adequate diets containing fructose or starch

    SciTech Connect

    Scholfield, D.J.; Fields, M.; Beal, T.; Lewis, C.G.; Behall, K.M. )

    1989-02-09

    The symptoms of copper (Cu) deficiency are known to be more severe when rats are fed a diet with fructose (F) as the principal carbohydrate. Mortality, in males, due to cardiac abnormalities usually occurs after five weeks of a 62% F, 0.6 ppm Cu deficient diet. These effects are not observed if cornstarch (CS) is the carbohydrate (CHO) source. Studies with F containing diets have shown increased catecholamine (C) turnover rates while diets deficient in Cu result in decreased norepinephrine (N) levels in tissues. Dopamine B-hydroxylase (EC 1.14.17.1) is a Cu dependent enzyme which catalyzes the conversion of dopamine (D) to N. An experiment was designed to investigate the effects of CHO and dietary Cu on levels of three C in cardiac tissue. Thirty-two male and female Sprague-Dawley rats were fed Cu deficient or adequate diets with 60% of calories from F or CS for 6 weeks. N, epinephrine (E) and D were measured by HPLC. Statistical analysis indicates that Cu deficiency tends to decrease N levels, while having the reverse effect on E. D did not appear to change. These findings indicate that Cu deficiency but not dietary CHO can affect the concentration of N and E in rat cardiac tissue.

  8. Improved ASTM G72 Test Method for Ensuring Adequate Fuel-to-Oxidizer Ratios

    NASA Technical Reports Server (NTRS)

    Juarez, Alfredo; Harper, Susana Tapia

    2016-01-01

    The ASTM G72/G72M-15 Standard Test Method for Autogenous Ignition Temperature of Liquids and Solids in a High-Pressure Oxygen-Enriched Environment is currently used to evaluate materials for the ignition susceptibility driven by exposure to external heat in an enriched oxygen environment. Testing performed on highly volatile liquids such as cleaning solvents has proven problematic due to inconsistent test results (non-ignitions). Non-ignition results can be misinterpreted as favorable oxygen compatibility, although they are more likely associated with inadequate fuel-to-oxidizer ratios. Forced evaporation during purging and inadequate sample size were identified as two potential causes for inadequate available sample material during testing. In an effort to maintain adequate fuel-to-oxidizer ratios within the reaction vessel during test, several parameters were considered, including sample size, pretest sample chilling, pretest purging, and test pressure. Tests on a variety of solvents exhibiting a range of volatilities are presented in this paper. A proposed improvement to the standard test protocol as a result of this evaluation is also presented. Execution of the final proposed improved test protocol outlines an incremental step method of determining optimal conditions using increased sample sizes while considering test system safety limits. The proposed improved test method increases confidence in results obtained by utilizing the ASTM G72 autogenous ignition temperature test method and can aid in the oxygen compatibility assessment of highly volatile liquids and other conditions that may lead to false non-ignition results.

  9. Determination of the need for selenium by chicks fed practical diets adequate in vitamin E

    SciTech Connect

    Combs, G.F. Jr.; Su, Q.; Liu, C.H.; Sinisalo, M.; Combs, S.B.

    1986-03-01

    Experiments were conducted to compare the dietary needs for selenium (Se) by chicks fed either purified (amino acid-based) or practical (corn- and soy-based) diets that were adequate with respect to vitamin E (i.e., contained 100 IU/kg) and all other known nutrients with the single exception of Se (i.e., contained only 0.10 ppm Se). Studies were conducted in Ithaca using Single Comb White Leghorn chicks fed the purified basal diet and in Beijing using chicks of the same breed fed either the same purified basal diet or the practical diet formulated to be similar to that used in poultry production in some parts of China and the US. Results showed that each basal diet produced severe depletion of Se-dependent glutathione peroxidase (SeGSHpx) in plasma, liver and pancreas according to the same time-course, but that other consequences of severe uncomplicated Se deficiency were much more severe among chicks fed the purified diet (e.g., growth depression, pancreatic dysfunction as indicated by elevated plasma amylase and abnormal pancreatic histology). Chicks fed the practical Se-deficient diet showed reduced pancreas levels of copper, zinc and molybdenum and elevated plasma levels of iron; they required ca. 0.10 ppm dietary Se to sustain normal SeGSHpx in several tissues and to prevent elevated amylase in plasma. The dietary Se requirement of the chick is, therefore, estimated to be 0.10 ppm.

  10. PG medical training and accreditation: responsibility of the government for the adequate health service delivery.

    PubMed

    Bhattarai, M D

    2012-09-01

    On one hand there is obvious inadequate health coverage to the rural population and on the other hand the densely populated urban area is facing the triple burden of increasing non-communicable and communicable health problems and the rising health cost. The postgraduate medical training is closely interrelated with the adequate health service delivery and health economics. In relation to the prevailing situation, the modern medical education trend indicates the five vital issues. These are i). Opportunity needs to be given to all MBBS graduates for General Specialist and Sub-Specialist Training inside the country to complete their medical education, ii). Urgent need for review of PG residential training criteria including appropriate bed and teacher criteria as well as entry criteria and eligibility criteria, iii). Involvement of all available units of hospitals fulfilling the requirements of the residential PG training criteria, iv). PG residential trainings involve doing the required work in the hospitals entitling them full pay and continuation of the service without any training fee or tuition fee, and v). Planning of the proportions of General Specialty and Sub-Specialty Training fields, particularly General Practice (GP) including its career and female participation. With increased number of medical graduates, now it seems possible to plan for optimal health coverage to the populations with appropriate postgraduate medical training. The medical professionals and public health workers must make the Government aware of the vital responsibility and the holistic approach required.

  11. Twenty-Four-Hour Urine Osmolality as a Physiological Index of Adequate Water Intake

    PubMed Central

    Perrier, Erica T.; Buendia-Jimenez, Inmaculada; Vecchio, Mariacristina; Armstrong, Lawrence E.; Tack, Ivan; Klein, Alexis

    2015-01-01

    While associations exist between water, hydration, and disease risk, research quantifying the dose-response effect of water on health is limited. Thus, the water intake necessary to maintain optimal hydration from a physiological and health standpoint remains unclear. The aim of this analysis was to derive a 24 h urine osmolality (UOsm) threshold that would provide an index of “optimal hydration,” sufficient to compensate water losses and also be biologically significant relative to the risk of disease. Ninety-five adults (31.5 ± 4.3 years, 23.2 ± 2.7 kg·m−2) collected 24 h urine, provided morning blood samples, and completed food and fluid intake diaries over 3 consecutive weekdays. A UOsm threshold was derived using 3 approaches, taking into account European dietary reference values for water; total fluid intake, and urine volumes associated with reduced risk for lithiasis and chronic kidney disease and plasma vasopressin concentration. The aggregate of these approaches suggest that a 24 h urine osmolality ≤500 mOsm·kg−1 may be a simple indicator of optimal hydration, representing a total daily fluid intake adequate to compensate for daily losses, ensure urinary output sufficient to reduce the risk of urolithiasis and renal function decline, and avoid elevated plasma vasopressin concentrations mediating the increased antidiuretic effort. PMID:25866433

  12. Household-level technologies to improve the availability and preparation of adequate and safe complementary foods.

    PubMed

    Mensah, Patience; Tomkins, Andrew

    2003-03-01

    Plant-based complementary foods are the main source of nutrients for many young children in developing countries. They may, however, present problems in providing nutritionally adequate and safe diets for older infants and young children. The high starch content leads to low-nutrient diets that are bulky and dense, with high levels of antinutritive factors such as phytates, tannins, lectins, and enzyme inhibitors. Phytates impair mineral bioavailability, lectins interfere with intestinal structure, and enzyme inhibitors inhibit digestive enzymes. In addition, there is often microbial contamination, which leads to diarrhea, growth-faltering, and impaired development, and the presence of chemical contaminants may lead to neurological disease and goiter. The fact that some fruits containing carotenoids are only available seasonally contributes to the vulnerability of children receiving predominantly plant-based diets. Traditional household food technologies have been used for centuries to improve the quality and safety of complementary foods. These include dehulling, peeling, soaking, germination, fermentation, and drying. While modern communities tend to reject these technologies in favor of more convenient fast-food preparations, there is now a resurgence of interest in older technologies as a possible means of improving the quality and safety of complementary foods when the basic diet cannot be changed for economic reasons. This paper describes the biology, safety, practicability, and acceptability of these traditional processes at the household or community level, as well as the gaps in research, so that more effective policies and programs can be implemented to improve the quality and safety of complementary foods.

  13. Salt, blood pressure and cardiovascular risk: what is the most adequate preventive strategy? A Swiss perspective

    PubMed Central

    Burnier, Michel; Wuerzner, Gregoire; Bochud, Murielle

    2015-01-01

    Among the various strategies to reduce the incidence of non-communicable diseases reduction of sodium intake in the general population has been recognized as one of the most cost-effective means because of its potential impact on the development of hypertension and cardiovascular diseases. Yet, this strategic health recommendation of the WHO and many other international organizations is far from being universally accepted. Indeed, there are still several unresolved scientific and epidemiological questions that maintain an ongoing debate. Thus what is the adequate low level of sodium intake to recommend to the general population and whether national strategies should be oriented to the overall population or only to higher risk fractions of the population such as salt-sensitive patients are still discussed. In this paper, we shall review the recent results of the literature regarding salt, blood pressure and cardiovascular risk and we present the recommendations recently proposed by a group of experts of Switzerland. The propositions of the participating medical societies are to encourage national health authorities to continue their discussion with the food industry in order to reduce the sodium intake of food products with a target of mean salt intake of 5–6 grams per day in the population. Moreover, all initiatives to increase the information on the effect of salt on health and on the salt content of food are supported. PMID:26321959

  14. Neurocysticercosis, familial cerebral cavernomas and intracranial calcifications: differential diagnosis for adequate management.

    PubMed

    Gasparetto, Emerson Leandro; Alves-Leon, Soniza; Domingues, Flavio Sampaio; Frossard, João Thiago; Lopes, Selva Paraguassu; Souza, Jorge Marcondes de

    2016-06-01

    Neurocysticercosis (NCC) is an endemic disease and important public health problem in some areas of the World and epilepsy is the most common neurological manifestation. Multiple intracranial lesions, commonly calcified, are seen on cranial computed tomography (CT) in the chronic phase of the disease and considered one of the diagnostic criteria of the diagnosis. Magnetic resonance imaging (MRI) is the test that better depicts the different stages of the intracranial cysts but does not show clearly calcified lesions. Cerebral cavernous malformations (CCM), also known as cerebral cavernomas, are frequent vascular malformations of the brain, better demonstrated by MRI and have also epilepsy as the main form of clinical presentation. When occurring in the familial form, cerebral cavernomas typically present with multiple lesions throughout the brain and, very often, with foci of calcifications in the lesions when submitted to the CT imaging. In the countries, and geographic areas, where NCC is established as an endemic health problem and neuroimaging screening is done by CT scan, it will be important to consider the differential diagnosis between the two diseases due to the differences in adequate management.

  15. Neurocysticercosis, familial cerebral cavernomas and intracranial calcifications: differential diagnosis for adequate management.

    PubMed

    Gasparetto, Emerson Leandro; Alves-Leon, Soniza; Domingues, Flavio Sampaio; Frossard, João Thiago; Lopes, Selva Paraguassu; Souza, Jorge Marcondes de

    2016-06-01

    Neurocysticercosis (NCC) is an endemic disease and important public health problem in some areas of the World and epilepsy is the most common neurological manifestation. Multiple intracranial lesions, commonly calcified, are seen on cranial computed tomography (CT) in the chronic phase of the disease and considered one of the diagnostic criteria of the diagnosis. Magnetic resonance imaging (MRI) is the test that better depicts the different stages of the intracranial cysts but does not show clearly calcified lesions. Cerebral cavernous malformations (CCM), also known as cerebral cavernomas, are frequent vascular malformations of the brain, better demonstrated by MRI and have also epilepsy as the main form of clinical presentation. When occurring in the familial form, cerebral cavernomas typically present with multiple lesions throughout the brain and, very often, with foci of calcifications in the lesions when submitted to the CT imaging. In the countries, and geographic areas, where NCC is established as an endemic health problem and neuroimaging screening is done by CT scan, it will be important to consider the differential diagnosis between the two diseases due to the differences in adequate management. PMID:27332076

  16. [Level of awareness and the adequate application of sunscreen by beauticians].

    PubMed

    Cortez, Diógenes Aparício Garcia; Machado, Érica Simionato; Vermelho, Sonia Cristina Soares Dias; Teixeira, Jorge Juarez Vieira; Cortez, Lucia Elaine Ranieri

    2016-06-01

    The scope of this research was to establish the level of awareness of beauticians regarding the importance of the application of sunscreen and to identify whether their patients had been properly instructed by these professionals. It involved a descriptive and exploratory study with interviews applying qualitative methodology among 30 beauticians. Data were gathered using the semi-structured interview technique in Maringá, in the southern state of Paraná. The data were analyzed using Atlas.ti software after applying quantitative analysis and response classification. Of those interviewed, 83.33% had a degree in Aesthetics, 20% attended ongoing training activities on sunscreen and 73.17% acquired sunscreen for its quality, though 86.67% were not familiar with sunscreens with natural anti-free radical components. Of those interviewed, 80% had never treated patients with skin cancer, though they reported having knowledge of care in relation to sun exposure and how to use the sunscreen and the relationship of these practices with the disease. The results showed that the recommendations and use of sunscreen by beauticians and users has been conducted in an adequate and conscientious manner. PMID:27383359

  17. Evaluation of catheter-manometer systems for adequate intravascular blood pressure measurements in small animals.

    PubMed

    Idvall, J; Aronsen, K F; Lindström, K; Ulmsten, U

    1977-09-30

    Various catheter-manometer systems possible for intravascular blood pressure measurments on rats have been elaborated and tested in vitro and in vivo. Using a pressure-step calibrator, it was observed from in vitro studies that microtransducers had superior frequency response compared to conventional transducers. Of the catheters tested, Pe-90 tapered to a 40 mm tip with an inner diameter of 0.3 mm had the best frequency response as judged from fall and settling times. Because of the damping effect, tapering increased fall time to 1.8 ms, which was still quite acceptable. By the same token settling time was minimized to 22.4 ms. With a special calculation method the theoretical percentile fault of the recordings was estimated to be 9.66%. When the measurement error was calculated from the actual in vivo recordings, it was found to be no more than 2.7%. These results show that the technique described is adequate for continuous intravascular blood pressure recordings on small animals. Finally it is emphasized that careful handling of the catheters and avoidance of stopcocks and air bubbles are essential for obtaining accurate and reproducible values. PMID:928971

  18. A high UV environment does not ensure adequate Vitamin D status

    NASA Astrophysics Data System (ADS)

    Kimlin, M. G.; Lang, C. A.; Brodie, A.; Harrison, S.; Nowak, M.; Moore, M. R.

    2006-12-01

    Queensland has the highest rates of skin cancer in the world and due to the high levels of solar UV in this region it is assumed that incidental UV exposure should provide adequate vitamin D status for the population. This research was undertaken to test this assumption among healthy free-living adults in south-east Queensland, Australia (27°S), at the end of winter. This research was approved by Queensland University of Technology Human Research Ethics Committee and conducted under the guidelines of the Declaration of Helsinki. 10.2% of the sample had serum vitamin D levels below 25nm/L (deficiency) and a further 32.3% had levels between 25nm/L and 50nm/L (insufficiency). Vitamin D deficiency and insufficiency can occur at the end of winter, even in sunny climates. The wintertime UV levels in south-east Queensland (UV index 4-6) are equivalent to summertime UV levels in northern regions of Europe and the USA. These ambient UV levels are sufficient to ensure synthesis of vitamin D requirements. We investigated individual UV exposure (through a self reported sun exposure questionnaire) and found correlations between exposure and Vitamin D status. Further research is needed to explore the interactions between the solar UV environment and vitamin D status, particularly in high UV environments, such as Queensland.

  19. The placental pursuit for an adequate oxidant balance between the mother and the fetus

    PubMed Central

    Herrera, Emilio A.; Krause, Bernardo; Ebensperger, German; Reyes, Roberto V.; Casanello, Paola; Parra-Cordero, Mauro; Llanos, Anibal J.

    2014-01-01

    The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled. PMID:25009498

  20. Aurally-adequate time-frequency analysis for scattered sound in auditoria

    NASA Astrophysics Data System (ADS)

    Norris, Molly K.; Xiang, Ning; Kleiner, Mendel

    2005-04-01

    The goal of this work was to apply an aurally-adequate time-frequency analysis technique to the analysis of sound scattering effects in auditoria. Time-frequency representations were developed as a motivated effort that takes into account binaural hearing, with a specific implementation of interaural cross-correlation process. A model of the human auditory system was implemented in the MATLAB platform based on two previous models [A. Härmä and K. Palomäki, HUTear, Espoo, Finland; and M. A. Akeroyd, A. Binaural Cross-correlogram Toolbox for MATLAB (2001), University of Sussex, Brighton]. These stages include proper frequency selectivity, the conversion of the mechanical motion of the basilar membrane to neural impulses, and binaural hearing effects. The model was then used in the analysis of room impulse responses with varying scattering characteristics. This paper discusses the analysis results using simulated and measured room impulse responses. [Work supported by the Frank H. and Eva B. Buck Foundation.

  1. Dihydrochalcomycin Production and Glycosyltransferase from Streptomyces SP. KCTC 0041BP

    PubMed Central

    Thuy, Ta Thi Thu; Sohng, Jae Kyung; Pfeifer, Blaine

    2010-01-01

    The dihydrochalcomycin (GERI) synthetic gene cluster from Streptomyces sp. KCTC 0041BP has been isolated. Two open reading frames (ORFs), designated gerT1 and gerT2 as glycosyltransferase genes, has been identified by sequence analysis. GerT1 encodes for the protein function as dTDP-deoxyallosyltransferase and it is responsible to the attachment of dTDP-allose to the macrolide ring. Similarly, gerT2 encodes for peptide named as dTDP-chacosyltransferase which can transfers the dTDP-4,6-dideoxyglucose to macrolactone core. During process of compound isolation, a new compound has been isolated with molecular weight m/z 755 [M+Na+]. This compound could be the dihydrochalcomycin derivative. The compound has been shown the same antibacterial activity as GERI compound.

  2. BP Cherry Point Cogeneration Project, Draft Environmental Impact Statement

    SciTech Connect

    N /A

    2003-09-19

    BP West Coast Products, LLC (BP or the Applicant) proposes to construct and operate a nominal 720-megawatt (MW), natural-gas-fired, combined-cycle cogeneration facility next to the existing BP Cherry Point Refinery in Whatcom County, Washington. The Applicant also owns and operates the refinery, but the cogeneration facility and the refinery would be operated as separate business units. The cogeneration facility and its ancillary infrastructure would provide steam and 85 MW of electricity to meet the operating needs of the refinery and 635 MW of electrical power for local and regional consumption. The proposed cogeneration facility would be located between Ferndale and Blaine in northwestern Whatcom County, Washington. The Canadian border is approximately 8 miles north of the proposed project site. The Washington State Energy Facility Site Evaluation Council (EFSEC) has jurisdiction over the evaluation of major energy facilities including the proposed project. As such, EFSEC will recommend approval or denial of the proposed cogeneration facility to the governor of Washington after an environmental review. On June 3, 2002, the Applicant filed an Application for Site Certification (ASC No. 2002-01) with EFSEC in accordance with Washington Administrative Code (WAC) 463-42. On April 22, 2003, the Applicant submitted an amended ASC that included, among other things, a change from air to water cooling. With the submission of the ASC and in accordance with the State Environmental Policy Act (SEPA) (WAC 463-47), EFSEC is evaluating the siting of the proposed project and conducting an environmental review with this Environmental Impact Statement (EIS). Because the proposed project requires federal agency approvals and permits, this EIS is intended to meet the requirements under both SEPA and the National Environmental Policy Act (NEPA). The Bonneville Power Administration (Bonneville) and U.S. Army Corps of Engineers (Corps) also will use this EIS as part of their

  3. Involving regional expertise in nationwide modeling for adequate prediction of climate change effects on different demands for fresh water

    NASA Astrophysics Data System (ADS)

    de Lange, W. J.

    2014-05-01

    Wim J. de Lange, Geert F. Prinsen, Jacco H. Hoogewoud, Ab A Veldhuizen, Joachim Hunink, Erik F.W. Ruijgh, Timo Kroon Nationwide modeling aims to produce a balanced distribution of climate change effects (e.g. harm on crops) and possible compensation (e.g. volume fresh water) based on consistent calculation. The present work is based on the Netherlands Hydrological Instrument (NHI, www.nhi.nu), which is a national, integrated, hydrological model that simulates distribution, flow and storage of all water in the surface water and groundwater systems. The instrument is developed to assess the impact on water use on land-surface (sprinkling crops, drinking water) and in surface water (navigation, cooling). The regional expertise involved in the development of NHI come from all parties involved in the use, production and management of water, such as waterboards, drinking water supply companies, provinces, ngo's, and so on. Adequate prediction implies that the model computes changes in the order of magnitude that is relevant to the effects. In scenarios related to drought, adequate prediction applies to the water demand and the hydrological effects during average, dry, very dry and extremely dry periods. The NHI acts as a part of the so-called Deltamodel (www.deltamodel.nl), which aims to predict effects and compensating measures of climate change both on safety against flooding and on water shortage during drought. To assess the effects, a limited number of well-defined scenarios is used within the Deltamodel. The effects on demand of fresh water consist of an increase of the demand e.g. for surface water level control to prevent dike burst, for flushing salt in ditches, for sprinkling of crops, for preserving wet nature and so on. Many of the effects are dealt with by regional and local parties. Therefore, these parties have large interest in the outcome of the scenario analyses. They are participating in the assessment of the NHI previous to the start of the analyses

  4. Involving regional expertise in nationwide modeling for adequate prediction of climate change effects on different demands for fresh water

    NASA Astrophysics Data System (ADS)

    de Lange, Wim; Prinsen, Geert.; Hoogewoud, Jacco; Veldhuizen, Ab; Ruijgh, Erik; Kroon, Timo

    2013-04-01

    Nationwide modeling aims to produce a balanced distribution of climate change effects (e.g. harm on crops) and possible compensation (e.g. volume fresh water) based on consistent calculation. The present work is based on the Netherlands Hydrological Instrument (NHI, www.nhi.nu), which is a national, integrated, hydrological model that simulates distribution, flow and storage of all water in the surface water and groundwater systems. The instrument is developed to assess the impact on water use on land-surface (sprinkling crops, drinking water) and in surface water (navigation, cooling). The regional expertise involved in the development of NHI come from all parties involved in the use, production and management of water, such as waterboards, drinking water supply companies, provinces, ngo's, and so on. Adequate prediction implies that the model computes changes in the order of magnitude that is relevant to the effects. In scenarios related to drought, adequate prediction applies to the water demand and the hydrological effects during average, dry, very dry and extremely dry periods. The NHI acts as a part of the so-called Deltamodel (www.deltamodel.nl), which aims to predict effects and compensating measures of climate change both on safety against flooding and on water shortage during drought. To assess the effects, a limited number of well-defined scenarios is used within the Deltamodel. The effects on demand of fresh water consist of an increase of the demand e.g. for surface water level control to prevent dike burst, for flushing salt in ditches, for sprinkling of crops, for preserving wet nature and so on. Many of the effects are dealt with? by regional and local parties. Therefore, these parties have large interest in the outcome of the scenario analyses. They are participating in the assessment of the NHI previous to the start of the analyses. Regional expertise is welcomed in the calibration phase of NHI. It aims to reduce uncertainties by improving the

  5. A 160-bp palindrome is a Rad50.Rad32-dependent mitotic recombination hotspot in Schizosaccharomyces pombe.

    PubMed Central

    Farah, Joseph A; Hartsuiker, Edgar; Mizuno, Ken-Ichi; Ohta, Kunihiro; Smith, Gerald R

    2002-01-01

    Palindromic sequences can form hairpin and cruciform structures that pose a threat to genome integrity. We found that a 160-bp palindrome (an inverted repeat of 80 bp) conferred a mitotic recombination hotspot relative to a control nonpalindromic sequence when inserted into the ade6 gene of Schizosaccharomyces pombe. The hotspot activity of the palindrome, but not the basal level of recombination, was abolished by a rad50 deletion, by a rad50S "separation of function" mutation, or by a rad32-D25A mutation in the nuclease domain of the Rad32 protein, an Mre11 homolog. We propose that upon extrusion of the palindrome the Rad50.Rad32 nuclease complex recognizes and cleaves the secondary structure thus formed and generates a recombinogenic break in the DNA. PMID:12019258

  6. How many hypertensive patients can be controlled in “real life”: an improvement strategy in primary care

    PubMed Central

    2013-01-01

    Background It is well known that hypertension control is non-satisfactory, but it is not clear how many hypertensive patients can be controlled in real life. We addressed this question implementing a simple, multifaceted improvement strategy in family practice. Methods Eighteen General Practitioner (GPs) agreed upon a simple improvement strategy including: 1) the use of occasional direct/indirect contacts (prescription refilling) to decrease missing blood pressure (BP) recording, and to increase therapeutic adherence, 2) the use of home BP measurements in non-controlled patients, 3) the addition of a new drug in non-controlled, but adequately adherent patients. Results were assessed after one year by automatic data extraction from the clinical records of all hypertensive subjects. Results The patients with a diagnosis of hypertension increased from 6.309 (age 58.5 +/- 12.4; M 45.5%) to 6.717 (age 58.6 +/- 12.9; M 45.7%): prevalence 25.3% to 27.0%. The BP recording increased: 4,305 patients (68.2%) vs 4,948 patients (78.4%) (+ 10.2%, ci 9.4%-10.9%; p < 0.001), as well as the BP control: 3,203 (50.8% of all the diagnosed hypertensive patients and 74.4% of the subjects with recorded BP value) vs 4,043 (64.1% of all the diagnosed hypertensive patients and 81.7% of the subjects with recorded BP value) (+ 13.3%, ci 12.5%-14.2%; p < 0.001 and + 7.3%, ci 6.7%-8.0%; p < 0.001). Conclusions Almost 82% of hypertensive subjects who contact their doctors can be easily controlled. Most non-controlled patients simply don’t see their GPs; in almost all the remaining non-controlled patients GPs fail to increase drug therapy. A further improvement is therefore possible. PMID:24330411

  7. 4E-BP1 regulates the differentiation of white adipose tissue.

    PubMed

    Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

    2013-07-01

    4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues.

  8. Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication.

    PubMed

    Xu, Yongpeng; Wang, Shuo; Jiang, Lulu; Wang, Hui; Yang, Yilin; Li, Ming; Wang, Xujing; Zhao, Xiulan; Xie, Keqin

    2016-01-01

    1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenousantioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1-BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1-BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin.We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect. PMID:26817862

  9. Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication

    PubMed Central

    Xu, Yongpeng; Wang, Shuo; Jiang, Lulu; Wang, Hui; Yang, Yilin; Li, Ming; Wang, Xujing; Zhao, Xiulan; Xie, Keqin

    2016-01-01

    Abstract 1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenous antioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1-BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1-BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin. We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect. PMID:26817862

  10. Effects of 4E-BP1 expression on hypoxic cell cycle inhibition and tumor cell proliferation and survival

    PubMed Central

    Barnhart, Bryan C.; Lam, Jennifer C.; Young, Regina M.; Houghton, Peter J.; Keith, Brian; Simon, M. Celeste

    2008-01-01

    Elevated activity of the eIF4F complex, which controls initiation of cap-dependent mRNA translation, has been linked to cancer progression. eIF4E recruitment to eIF4F is the rate limiting step of complex assembly and is regulated by eIF4E-Binding Proteins (4E-BPs). When stimulated, the mammalian Target of Rapamycin complex 1 (mTORC1) phosphorylates 4E-BP1, which then releases eIF4E. Hypoxia inhibits mTORC1 activity and therefore cap-dependent protein synthesis. To establish a novel genetic test of the role of eIF4F activity in regulating cell division and viability within hypoxic tumor microenvironments, we generated shRNA mediated 4E-BP1 knock-down in Rh30 rhabdomyosarcoma cells. 4E-BP1 knock-down relieved hypoxia-mediated inhibition of cycle progression in vitro and was correlated with increased expression of cyclin D1 and c-Myc. Xenograft tumors derived from these cells also displayed enhanced expression of cyclin D1 and c-Myc along with antiapoptotic genes encoding Bcl-xL, and XIAP, and failed to develop the extensive necrotic zones and edema observed in control tumors. Surprisingly, 4E-BP1 knock-down also leads to a dramatic increase in aberrant mitoses in vivo and enhanced expression of Mad2 and securin. Thus, reduced expression of the negative regulator of eIF4E has significant effects on tumor development, and is associated with enhanced cell proliferation and survival. PMID:18708753

  11. Microbial Consumption of Natural Gases Released from the BP Deepwater Horizon Oil Spill

    NASA Astrophysics Data System (ADS)

    Mendes, S. D.; Valentine, D. L.; Farwell, C.

    2010-12-01

    The BP Deepwater Horizon disaster caused the release of natural gas, which dissolved in the water column to form gas plumes. Containing methane, ethane, and propane, these gas plumes fuel microbial respiration. This work targeted the water column to quantify the maximum rate of microbial respiration in the natural gas plume. A novel method using uniformly 13C-labeled substrates as tracers was applied to determine the rate of microbial consumption of these gases in water surrounding the impacted area. Consumption rate experiments were performed on board the R/V Cape Hatteras (July 12-20, 2010) and analyzed using an isotope ratio mass spectrometer (IRMS). The kinetic order and maximum consumption rate of the microbial community were determined by experimental controls using the 13C-labeled tracers in temperature, time, and concentration series. Ongoing sampling efforts allow changes in the response of the microbial community to be monitored over time.

  12. Do Foley Catheters Adequately Drain the Bladder? Evidence from CT Imaging Studies

    PubMed Central

    Avulova, Svetlana; Li, Valery J.; Khusid, Johnathan A.; Choi, Woo S.; Weiss, Jeffrey P.

    2015-01-01

    ABSTRACT Introduction: The Foley catheter has been widely assumed to be an effective means of draining the bladder. However, recent studies have brought into question its efficacy. The objective of our study is to further assess the adequacy of Foley catheter for complete drainage of the bladder. Materials and Methods: Consecutive catheterized patients were identified from a retrospective review of contrast enhanced and non-contrast enhanced computed tomo-graphic (CT) abdomen and pelvis studies completed from 7/1/2011-6/30/2012. Residual urine volume (RUV) was measured using 5mm axial CT sections as follows: The length (L) and width (W) of the bladder in the section with the greatest cross sectional area was combined with bladder height (H) as determined by multiplanar reformatted images in order to calculate RUV by applying the formula for the volume (V) of a sphere in a cube: V=(ϖ/6)*(L*W*H). Results: RUVs of 167 (mean age 67) consecutively catheterized men (n=72) and women (n=95) identified by CT abdomen and pelvis studies were calculated. The mean RUV was 13.2 mL (range: 0.0 mL-859.1 mL, standard deviation: 75.9 mL, margin of error at 95% confidence:11.6 mL). Four (2.4%) catheterized patients had RUVs of >50 mL, two of whom had an improperly placed catheter tip noted on their CT-reports. Conclusions: Previous studies have shown that up to 43% of catheterized patients had a RUV greater than 50 mL, suggesting inadequacy of bladder drainage via the Foley catheter. Our study indicated that the vast majority of patients with Foley catheters (97.6%), had adequately drained bladders with volumes of <50 mL. PMID:26200550

  13. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study

    PubMed Central

    Goutianos, Georgios; Tzioura, Aikaterini; Kyparos, Antonios; Paschalis, Vassilis; Margaritelis, Nikos V; Veskoukis, Aristidis S; Zafeiridis, Andreas; Dipla, Konstantina; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2015-01-01

    Animal models are widely used in biology and the findings of animal research are traditionally projected to humans. However, recent publications have raised concerns with regard to what extent animals and humans respond similar to physiological stimuli. Original data on direct in vivo comparison between animals and humans are scarce and no study has addressed this issue after exercise. We aimed to compare side by side in the same experimental setup rat and human responses to an acute exercise bout of matched intensity and duration. Rats and humans ran on a treadmill at 86% of maximal velocity until exhaustion. Pre and post exercise we measured 30 blood chemistry parameters, which evaluate iron status, lipid profile, glucose regulation, protein metabolism, liver, and renal function. ANOVA indicated that almost all biochemical parameters followed a similar alteration pattern post exercise in rats and humans. In fact, there were only 2/30 significant species × exercise interactions (in testosterone and globulins), indicating different responses to exercise between rats and humans. On the contrary, the main effect of exercise was significant in 15/30 parameters and marginally nonsignificant in other two parameters (copper, P = 0.060 and apolipoprotein B, P = 0.058). Our major finding is that the rat adequately mimics human responses to exercise in those basic blood biochemical parameters reported here. The physiological resemblance of rat and human blood responses after exercise to exhaustion on a treadmill indicates that the use of blood chemistry in rats for exercise physiology research is justified. PMID:25677548

  14. When are studies adequate for regulatory purposes? View of one regulated.

    PubMed Central

    Bundy, M

    1981-01-01

    The question of adequacy of studies for regulatory purposes has been debated for years. Nine questions need answers to determine adequacy: (1) Does the study deal with a defined problem or a defined segment of it? (2) Do the study data justify the conclusions drawn? (3) Were appropriate statistical analyses used? Is there evidence of bias versus objectivity in the collection or analysis of data? (4) Does the study support, supplement (or complement) or refute information in the literature? Is the study truly new information? (5) Does the study conform to the Interagency Regulatory Liaison Group (IRLG) guidelines for documentation of Epidemiologic Studies? (6) Does the study stand up to peer review? (7) Have other investigators been able to confirm the findings by duplicating the study? (8) Is the study acceptable or can it be made acceptable for publication in a reputable scientific journal? (9) Is the problem of such magnitude or significance that regulation is required? Because there is no such thing as a risk-free environment or absolute safety and there is no definitive "yes" answer to each of the questions, the regulated would hope--yes, insist--that the regulators exercise judgement with great skill in promulgation of rules or regulations. The application of safety factors and the determination of acceptable levels of risk should be social decisions. A discussion of instances where the "regulated" believes that studies have not been adequate, or others habe been ignored, or misinterpreted for regulatory purposes in included.A method of settling controversial questions to eliminate the litigation route is proposed. Judgment which is so often eliminated by regulation needs to find its way back into the regulatory process. The regulated recognize the need for regulations. However, when these regulations are based on less than good scientific judgment, harm will be done to the regulatory process itself in the long run. PMID:7333262

  15. Prioritising pharmaceuticals for environmental risk assessment: Towards adequate and feasible first-tier selection.

    PubMed

    Roos, V; Gunnarsson, L; Fick, J; Larsson, D G J; Rudén, C

    2012-04-01

    The presence of pharmaceuticals in the aquatic environment, and the concerns for negative effects on aquatic organisms, has gained increasing attention over the last years. As ecotoxicity data are lacking for most active pharmaceutical ingredients (APIs), it is important to identify strategies to prioritise APIs for ecotoxicity testing and environmental monitoring. We have used nine previously proposed prioritisation schemes, both risk- and hazard-based, to rank 582 APIs. The similarities and differences in overall ranking results and input data were compared. Moreover, we analysed how well the methods ranked seven relatively well-studied APIs. It is concluded that the hazard-based methods were more successful in correctly ranking the well-studied APIs, but the fish plasma model, which includes human pharmacological data, also showed a high success rate. The results of the analyses show that the input data availability vary significantly; some data, such as logP, are available for most API while information about environmental concentrations and bioconcentration are still scarce. The results also suggest that the exposure estimates in risk-based methods need to be improved and that the inclusion of effect measures at first-tier prioritisation might underestimate risks. It is proposed that in order to develop an adequate prioritisation scheme, improved data on exposure such as degradation and sewage treatment removal and bioconcentration ability should be further considered. The use of ATC codes may also be useful for the development of a prioritisation scheme that includes the mode of action of pharmaceuticals and, to some extent, mixture effects. PMID:22361586

  16. Determining median urinary iodine concentration that indicates adequate iodine intake at population level.

    PubMed Central

    Delange, François; de Benoist, Bruno; Burgi, Hans

    2002-01-01

    OBJECTIVE: Urinary iodine concentration is the prime indicator of nutritional iodine status and is used to evaluate population-based iodine supplementation. In 1994, WHO, UNICEF and ICCIDD recommended median urinary iodine concentrations for populations of 100- 200 micro g/l, assuming the 100 micro g/l threshold would limit concentrations <50 micro g/l to 100 micro g/l. The total population was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine concentrations were 111-540 (median 201) micro g/l for all populations, 100-199 micro g/l in 23 (48%) populations and >/=200 micro g/l in 25 (52%). The frequencies of values <50 micro g/l were 0-20.8 (mean 4.8%) overall and 7.2% and 2.5% in populations with medians of 100-199 micro g/l and >200 micro g/l, respectively. The frequency reached 20% only in two places where iodine had been supplemented for <2 years. CONCLUSION: The frequency of urinary iodine concentrations <50 micro g/l in populations with median urinary iodine concentrations >/=100 micro g/l has been overestimated. The threshold of 100 micro g/l does not need to be increased. In populations, median urinary iodine concentrations of 100-200 micro g/l indicate adequate iodine intake and optimal iodine nutrition. PMID:12219154

  17. The adequate stimulus for avian short latency vestibular responses to linear translation

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Jones, S. M.; Colbert, S.

    1998-01-01

    Transient linear acceleration stimuli have been shown to elicit eighth nerve vestibular compound action potentials in birds and mammals. The present study was undertaken to better define the nature of the adequate stimulus for neurons generating the response in the chicken (Gallus domesticus). In particular, the study evaluated the question of whether the neurons studied are most sensitive to the maximum level of linear acceleration achieved or to the rate of change in acceleration (da/dt, or jerk). To do this, vestibular response thresholds were measured as a function of stimulus onset slope. Traditional computer signal averaging was used to record responses to pulsed linear acceleration stimuli. Stimulus onset slope was systematically varied. Acceleration thresholds decreased with increasing stimulus onset slope (decreasing stimulus rise time). When stimuli were expressed in units of jerk (g/ms), thresholds were virtually constant for all stimulus rise times. Moreover, stimuli having identical jerk magnitudes but widely varying peak acceleration levels produced virtually identical responses. Vestibular response thresholds, latencies and amplitudes appear to be determined strictly by stimulus jerk magnitudes. Stimulus attributes such as peak acceleration or rise time alone do not provide sufficient information to predict response parameter quantities. Indeed, the major response parameters were shown to be virtually independent of peak acceleration levels or rise time when these stimulus features were isolated and considered separately. It is concluded that the neurons generating short latency vestibular evoked potentials do so as "jerk encoders" in the chicken. Primary afferents classified as "irregular", and which traditionally fall into the broad category of "dynamic" or "phasic" neurons, would seem to be the most likely candidates for the neural generators of short latency vestibular compound action potentials.

  18. [Bone and joint diseases in children. Adequate calcium intake and dietary habit especially breakfast in children and adolescents].

    PubMed

    Kodama, Momoko; Uenishi, Kazuhiro

    2010-06-01

    Childhood and adolescence are important periods for body growth. Calcium is one of the critical dietary factors especially for bone growth. Although recommended dietary allowance (RDA) of calcium has been determined higher in Dietary reference intakes for Japanese, 2010, calcium intake of Japanese children and adolescent are not necessarily adequate. Furthermore, breakfast skippers in this period tend to increase. So, it is very important to acquire an adequate dietary habit from childhood and adolescent. PMID:20513944

  19. Porcine SOX9 Gene Expression Is Influenced by an 18bp Indel in the 5’-Untranslated Region

    PubMed Central

    Xing, Yuyun; Ding, Nengshui; Huang, Lusheng; Schütz, Ekkehard

    2015-01-01

    Sex determining region Y-box 9 (SOX9) is an important regulator of sex and skeletal development and is expressed in a variety of embryonal and adult tissues. Loss or gain of function resulting from mutations within the coding region or chromosomal aberrations of the SOX9 locus lead to a plethora of detrimental phenotypes in humans and animals. One of these phenotypes is the so-called male-to-female or female-to-male sex-reversal which has been observed in several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex-reversal French Large White pigs, a genome-wide association study suggested SOX9 as the causal gene, although no functional mutations were identified in affected animals. However, besides others an 18bp indel had been detected in the 5′-untranslated region of the SOX9 gene by comparing affected animals and controls. We have identified the same indel (Δ18) between position +247bp and +266bp downstream the transcription start site of the porcine SOX9 gene in four other pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These animals have been genotyped in an attempt to identify candidate genes for porcine inguinal and/or scrotal hernia. Because the 18bp segment in the wild type 5′-UTR harbours a highly conserved cAMP-response element (CRE) half-site, we analysed its role in SOX9 expression in vitro. Competition and immunodepletion electromobility shift assays demonstrate that the CRE half-site is specifically recognized by CREB. Both binding of CREB to the wild type as well as the absence of the CRE half-site in Δ18 reduced expression efficiency in HEK293T, PK–15, and ATDC5 cells significantly. Transfection experiments of wild type and Δ18 SOX9 promoter luciferase constructs show a significant reduction of RNA and protein levels depending on the presence or absence of the 18bp segment. Hence, the data presented here demonstrate that the 18bp indel in the porcine SOX9 5′-UTR is of functional importance and

  20. Porcine SOX9 Gene Expression Is Influenced by an 18 bp Indel in the 5'-Untranslated Region.

    PubMed

    Brenig, Bertram; Duan, Yanyu; Xing, Yuyun; Ding, Nengshui; Huang, Lusheng; Schütz, Ekkehard

    2015-01-01

    Sex determining region Y-box 9 (SOX9) is an important regulator of sex and skeletal development and is expressed in a variety of embryonal and adult tissues. Loss or gain of function resulting from mutations within the coding region or chromosomal aberrations of the SOX9 locus lead to a plethora of detrimental phenotypes in humans and animals. One of these phenotypes is the so-called male-to-female or female-to-male sex-reversal which has been observed in several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex-reversal French Large White pigs, a genome-wide association study suggested SOX9 as the causal gene, although no functional mutations were identified in affected animals. However, besides others an 18 bp indel had been detected in the 5'-untranslated region of the SOX9 gene by comparing affected animals and controls. We have identified the same indel (Δ18) between position +247 bp and +266 bp downstream the transcription start site of the porcine SOX9 gene in four other pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These animals have been genotyped in an attempt to identify candidate genes for porcine inguinal and/or scrotal hernia. Because the 18 bp segment in the wild type 5'-UTR harbours a highly conserved cAMP-response element (CRE) half-site, we analysed its role in SOX9 expression in vitro. Competition and immunodepletion electromobility shift assays demonstrate that the CRE half-site is specifically recognized by CREB. Both binding of CREB to the wild type as well as the absence of the CRE half-site in Δ18 reduced expression efficiency in HEK293T, PK-15, and ATDC5 cells significantly. Transfection experiments of wild type and Δ18 SOX9 promoter luciferase constructs show a significant reduction of RNA and protein levels depending on the presence or absence of the 18 bp segment. Hence, the data presented here demonstrate that the 18 bp indel in the porcine SOX9 5'-UTR is of functional importance and may

  1. An analysis of the rapidly rotating Bp star HD 133880

    NASA Astrophysics Data System (ADS)

    Bailey, J. D.; Grunhut, J.; Shultz, M.; Wade, G.; Landstreet, J. D.; Bohlender, D.; Lim, J.; Wong, K.; Drake, S.; Linsky, J.

    2012-06-01

    HD 133880 is a rapidly rotating chemically peculiar B-type (Bp) star (v sin i≃ 103 km s-1) and is host to one of the strongest magnetic fields of any Ap/Bp star. A member of the Upper Centaurus Lupus association, it is a star with a well-determined age of 16 Myr. 12 new spectra, four of which are polarimetric, obtained from the FEROS, ESPaDOnS and HARPS instruments, provide sufficient material from which to re-evaluate the magnetic field and obtain a first approximation to the atmospheric abundance distributions of He, O, Mg, Si, Ti, Cr, Fe, Ni, Pr and Nd. An abundance analysis was carried out using ZEEMAN, a program which synthesizes spectral line profiles for stars with permeating magnetic fields. The magnetic field structure was characterized by a colinear multipole expansion from the observed variations of the longitudinal and surface fields with rotational phase. Both magnetic hemispheres are clearly visible during the stellar rotation, and thus a three-ring abundance distribution model encompassing both magnetic poles and magnetic equator with equal spans in colatitude was adopted. Using the new magnetic field measurements and optical photometry together with previously published data, we refine the period of HD 133880 to P= 0.877 476 ± 0.000 009 d. Our simple axisymmetric magnetic field model is based on a predominantly quadrupolar component that roughly describes the field variations. Using spectrum synthesis, we derived mean abundances for O, Mg, Si, Ti, Cr, Fe and Pr. All elements, except Mg, are overabundant compared to the Sun. Mg appears to be approximately uniform over the stellar surface, while all other elements are more abundant in the negative magnetic hemisphere than in the positive magnetic hemisphere. In contrast to most Ap/Bp stars which show an underabundance in O, in HD 133880 this element is clearly overabundant compared to the solar abundance ratio. In studying the Hα and Paschen lines in the optical spectra, we could not unambiguously

  2. Complete genome sequence of Bp7, an Escherichia coli bacteriophage with a wide host range.

    PubMed

    Zhang, Can; Liu, Wenhua; Ren, Huiying

    2012-12-01

    Chicken colibacillosis is caused by some pathogenic Escherichia coli strains. Thirty-five pathogenic antibiotic-resistant E. coli strains were used in the host range detection of bacteriophage Bp7. The phage showed a wide range of E. coli hosts (46%). The complete genome of bacteriophage Bp7 was sequenced, assembled, and analyzed. The results revealed a linear double-stranded DNA sequence of 168,066 bp harboring 791 open reading frames. The major findings from its annotation are described.

  3. Using L-M BP Algorithm Forecase the 305 Days Production of First-Breed Dairy

    NASA Astrophysics Data System (ADS)

    Wei, Xiaoli; Qi, Guoqiang; Shen, Weizheng; Jian, Sun

    Aiming at the shortage of conventional BP algorithm, a BP neural net works improved by L-M algorithm is put forward. On the basis of the network, a Prediction model for 305 day's milk productions was set up. Traditional methods finish these data must spend at least 305 days, But this model can forecast first-breed dairy's 305 days milk production ahead of 215 days. The validity of the improved BP neural network predictive model was validated through the experiments.

  4. Planning 4-Dimensional Computed Tomography (4DCT) Cannot Adequately Represent Daily Intrafractional Motion of Abdominal Tumors

    SciTech Connect

    Ge, Jiajia; Santanam, Lakshmi; Noel, Camille; Parikh, Parag J.

    2013-03-15

    Purpose: To evaluate whether planning 4-dimensional computed tomography (4DCT) can adequately represent daily motion of abdominal tumors in regularly fractionated and stereotactic body radiation therapy (SBRT) patients. Methods and Materials: Intrafractional tumor motion of 10 patients with abdominal tumors (4 pancreas-fractionated and 6 liver-stereotactic patients) with implanted fiducials was measured based on daily orthogonal fluoroscopic movies over 38 treatment fractions. The needed internal margin for at least 90% of tumor coverage was calculated based on a 95th and fifth percentile of daily 3-dimensional tumor motion. The planning internal margin was generated by fusing 4DCT motion from all phase bins. The disagreement between needed and planning internal margin was analyzed fraction by fraction in 3 motion axes (superior-inferior [SI], anterior-posterior [AP], and left-right [LR]). The 4DCT margin was considered as an overestimation/underestimation of daily motion when disagreement exceeded at least 3 mm in the SI axis and/or 1.2 mm in the AP and LR axes (4DCT image resolution). The underlying reasons for this disagreement were evaluated based on interfractional and intrafractional breathing variation. Results: The 4DCT overestimated daily 3-dimensional motion in 39% of the fractions in 7 of 10 patients and underestimated it in 53% of the fractions in 8 of 10 patients. Median underestimation was 3.9 mm, 3.0 mm, and 1.7 mm in the SI axis, AP axis, and LR axis, respectively. The 4DCT was found to capture irregular deep breaths in 3 of 10 patients, with 4DCT motion larger than mean daily amplitude by 18 to 21 mm. The breathing pattern varied from breath to breath and day to day. The intrafractional variation of amplitude was significantly larger than intrafractional variation (2.7 mm vs 1.3 mm) in the primary motion axis (ie, SI axis). The SBRT patients showed significantly larger intrafractional amplitude variation than fractionated patients (3.0 mm vs 2

  5. Shoulder Arthroscopy Does Not Adequately Visualize Pathology of the Long Head of Biceps Tendon

    PubMed Central

    Saithna, Adnan; Longo, Alison; Leiter, Jeff; Old, Jason; MacDonald, Peter M.

    2016-01-01

    Background: Pulling the long head of the biceps tendon into the joint at arthroscopy is a common method for evaluation of tendinopathic lesions. However, the rate of missed diagnoses when using this technique is reported to be as high as 30% to 50%. Hypothesis: Tendon excursion achieved using a standard arthroscopic probe does not allow adequate visualization of extra-articular sites of predilection of tendinopathy. Study Design: Descriptive laboratory study. Methods: Seven forequarter amputation cadaveric specimens were evaluated. The biceps tendon was tagged to mark the intra-articular length and the maximum excursions achieved using a probe and a grasper in both beach-chair and lateral positions. Statistical analyses were performed using analysis of variance to compare means. Results: The mean intra-articular and extra-articular lengths of the tendons were 23.9 and 82.3 mm, respectively. The length of tendon that could be visualized by pulling it into the joint with a probe through the anterior midglenoid portal was not significantly different when using either lateral decubitus (mean ± SD, 29.9 ± 3.89 mm; 95% CI, 25.7-34 mm) or beach-chair positions (32.7 ± 4.23 mm; 95% CI, 28.6-36.8 mm). The maximum length of the overall tendon visualized in any specimen using a standard technique was 37 mm. Although there was a trend to greater excursion using a grasper through the same portal, this was not statistically significant. However, using a grasper through the anterosuperior portal gave a significantly greater mean excursion than any other technique (46.7 ± 4.31 mm; 95% CI, 42.6-50.8 mm), but this still failed to allow evaluation of Denard zone C. Conclusion: Pulling the tendon into the joint with a probe via an anterior portal does not allow visualization of distal sites of predilection of pathology. Surgeons should be aware that this technique is inadequate and can result in missed diagnoses. Clinical Relevance: This study demonstrates that glenohumeral

  6. Global Uranium And Thorium Resources: Are They Adequate To Satisfy Demand Over The Next Half Century?

    NASA Astrophysics Data System (ADS)

    Lambert, I. B.

    2012-04-01

    This presentation will consider the adequacy of global uranium and thorium resources to meet realistic nuclear power demand scenarios over the next half century. It is presented on behalf of, and based on evaluations by, the Uranium Group - a joint initiative of the OECD Nuclear Energy Agency and the International Atomic Energy Agency, of which the author is a Vice Chair. The Uranium Group produces a biennial report on Uranium Resources, Production and Demand based on information from some 40 countries involved in the nuclear fuel cycle, which also briefly reviews thorium resources. Uranium: In 2008, world production of uranium amounted to almost 44,000 tonnes (tU). This supplied approximately three-quarters of world reactor requirements (approx. 59,000 tU), the remainder being met by previously mined uranium (so-called secondary sources). Information on availability of secondary sources - which include uranium from excess inventories, dismantling nuclear warheads, tails and spent fuel reprocessing - is incomplete, but such sources are expected to decrease in market importance after 2013. In 2008, the total world Reasonably Assured plus Inferred Resources of uranium (recoverable at less than 130/kgU) amounted to 5.4 million tonnes. In addition, it is clear that there are vast amounts of uranium recoverable at higher costs in known deposits, plus many as yet undiscovered deposits. The Uranium Group has concluded that the uranium resource base is more than adequate to meet projected high-case requirements for nuclear power for at least half a century. This conclusion does not assume increasing replacement of uranium by fuels from reprocessing current reactor wastes, or by thorium, nor greater reactor efficiencies, which are likely to ameliorate future uranium demand. However, progressively increasing quantities of uranium will need to be mined, against a backdrop of the relatively small number of producing facilities around the world, geopolitical uncertainties and

  7. Identification of a 49-bp fragment of the HvLTP2 promoter directing aleurone cell specific expression.

    PubMed

    Opsahl-Sorteberg, Hilde-Gunn; Divon, Hege Hvattum; Nielsen, Peter Stein; Kalla, Roger; Hammond-Kosack, Michael; Shimamoto, Ko; Kohli, Ajay

    2004-10-27

    Identification of regulatory elements directing definite and specific spatiotemporal expression patterns is a prerequisite to the next generation of transgenic plants with commercial and ethical feasibility for producing plantibodies or other pharmaceutically important compounds. Here we describe the functional dissection of the barley nonspecific lipid transfer protein gene promoter, HvLTP2. The gene is specifically expressed in aleurone cells of cereals and used as an aleurone marker in maize and rice. The transcript is uniformly localised in the barley aleurone cells from around 10 DAP. Patchy expression in aleurone cells of transgenic rice has been reported and explained by silencing of transgenes. We have performed deletion analyses of the 801-bp HvLTP2 promoter to gain insight into the molecular basis of its regulation and the presence of putative regulatory elements. From the deletion studies, a 49-bp promoter region directing aleurone-specific expression was identified. Simultaneously, in vivo footprinting was carried out to identify promoter elements bound by putative regulatory proteins. Within the 49-bp fragment, the most promising candidate for a minimal cis-acting regulatory region directing aleurone specificity is the ds-sequence. Based on our results, we hypothesise that the ds-sequence directs aleurone specificity, possibly through a concerted action with elements directing general expression in the seed. Moreover, we present an overview of LTP2 elements putatively involved in directing seed, endosperm, and aleurone expression. Additionally, we report HvLTP2 expression in the embryo, not previously detected. The regulatory element(s) directing expression in embryo is located downstream of the 49-bp fragment directing aleurone specificity, thus demonstrating independent control of aleurone and embryo-localised expression. Finally, we discuss the existence of several endosperm-specific boxes and whether alternative promoter elements and combinations

  8. The BP oil spill and the bounty of Plaquemines Parish.

    PubMed

    Fertel, Randy

    2011-01-01

    The source of 25 to 30 percent of America's seafood, the Mississippi River Delta's cornucopian world is now uncertain. And yet, even if shrimp, oysters, and finfish are unaffected by the BP Oil Spill - a big if - one can already reflect on the passing of the culture once built upon gathering them. For almost three centuries, levees made life possible along the riverbanks and in the wetlands beyond. Those same levees also ensured the wetlands would eventually melt away into the Gulf. Cutting off the silt left behind during annual river inundations subjected the fragile land to erosion. Sulfur, natural gas, and oil production companies dug twenty thousand miles of canals to gain more direct routes to their fields and to pump out their mineral wealth. This caused salt-water intrusion that killed off plant life and caused more erosion. The world that sustained my Plaquemines ancestors was less subject to collapse following disasters not only because the ecosystem before the wetlands' ongoing loss was then more vibrant, complex, and robust; but also because their lives, especially their culinary lives, were more vibrant, complex, and robust. Life was hard, but when it came to putting food on the table, life followed the seasons. PMID:21591308

  9. The BP oil spill and the bounty of Plaquemines Parish.

    PubMed

    Fertel, Randy

    2011-01-01

    The source of 25 to 30 percent of America's seafood, the Mississippi River Delta's cornucopian world is now uncertain. And yet, even if shrimp, oysters, and finfish are unaffected by the BP Oil Spill - a big if - one can already reflect on the passing of the culture once built upon gathering them. For almost three centuries, levees made life possible along the riverbanks and in the wetlands beyond. Those same levees also ensured the wetlands would eventually melt away into the Gulf. Cutting off the silt left behind during annual river inundations subjected the fragile land to erosion. Sulfur, natural gas, and oil production companies dug twenty thousand miles of canals to gain more direct routes to their fields and to pump out their mineral wealth. This caused salt-water intrusion that killed off plant life and caused more erosion. The world that sustained my Plaquemines ancestors was less subject to collapse following disasters not only because the ecosystem before the wetlands' ongoing loss was then more vibrant, complex, and robust; but also because their lives, especially their culinary lives, were more vibrant, complex, and robust. Life was hard, but when it came to putting food on the table, life followed the seasons.

  10. NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients

    PubMed Central

    Gonzalez Camargo, Rodolfo; Mendes dos Reis Riccardi, Daniela; Quintas Teixeira Ribeiro, Henrique; Carlos Carnevali, Luiz; Marques de Matos-Neto, Emidio; Enjiu, Lucas; Xavier Neves, Rodrigo; Darck Carola Correia Lima, Joanna; Galvão Figuerêdo, Raquel; Sérgio Martins de Alcântara, Paulo; Maximiano, Linda; Otoch, José; Batista, Miguel Luiz; Püschel, Gerhard; Seelaender, Marilia

    2015-01-01

    Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1β, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-κBp65 and its target genes expression (TNF-α, IL-1β, MCP-1 and IκB-α) were significantly higher in cachectic cancer patients. Moreover, NF-κBp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-κB pathway plays a role in the promotion of WAT inflammation during cachexia. PMID:26053616

  11. Design and characterization of novel antimicrobial peptides, R-BP100 and RW-BP100, with activity against Gram-negative and Gram-positive bacteria.

    PubMed

    Torcato, Inês M; Huang, Yen-Hua; Franquelim, Henri G; Gaspar, Diana; Craik, David J; Castanho, Miguel A R B; Troeira Henriques, Sónia

    2013-03-01

    BP100 is a short cationic antimicrobial peptide with a mechanism of action dependent on peptide-lipid interactions and microbial surface charge neutralization. Although active against Gram-negative bacteria, BP100 is inactive against Gram-positive bacteria. In this study we report two newly designed BP100 analogues, RW-BP100 and R-BP100 that have the Tyr residue replaced with a Trp and/or the Lys residues replaced with an Arg. The new analogues in addition to being active against Gram-negative bacteria, possess activity against all tested Gram-positive bacteria. Mechanistic studies using atomic force microscopy, surface plasmon resonance and fluorescence methodologies reveal that the antibacterial efficiency follows the affinity for bacterial membrane. The studies suggest that the activity of BP100 and its analogues against Gram-negative bacteria is mainly driven by electrostatic interactions with the lipopolysaccharide layer and is followed by binding to and disruption of the inner membrane, whereas activity against Gram-positive bacteria, in addition to electrostatic attraction to the exposed lipoteichoic acids, requires an ability to more deeply insert in the membrane environment, which is favoured with Arg residues and is facilitated in the presence of a Trp residue. Knowledge on the mechanism of action of these antimicrobial peptides provides information that assists in the design of antimicrobials with higher efficacy and broader spectra of action, but also on the design of peptides with higher specificity if required. PMID:23246973

  12. High-resolution study of planktic foraminifera from the eastern Mediterranean over the last 13 cal ka BP. Example from the Nile prodelta

    NASA Astrophysics Data System (ADS)

    Mojtahid, Meryem; Rose, Manceau; Ralf, Schiebel; Rick, Hennekam; Lange Gert, de

    2014-05-01

    A unique high-resolution record from the Nile prodelta has been investigated in order to study past hydrological and climatic changes in the southeastern Levantine region over the last 13 cal ka BP. To this end, we used planktic foraminifera (accumulation rates, diversity, assemblages and size properties) as bioindicators of the ecological characteristics of the water column (temperature, salinity, primary production and hydrology). These characteristics were mainly connected to Nile discharges and thermohaline circulation which in turn were controlled by various global and regional climatic forcing factors (e.g., orbital forcing, African and Indian Monsoon, North Atlantic Oscillation (NAO)). Our data showed seven main climatic periods: 1) from 13.0 to 11.5 cal ka BP encompassing the Younger Dryas and characterized by rather cold productive and mixed waters; 2) from 11.5 to 10.1 cal ka BP matching the start of the Holocene and the onset of the African Humid Period (AHP). This period was defined by surface water warming and increasing stratification due to increased river outflow; 3) from 10.1 to 6.4 cal ka BP encompassing the Sapropel deposit (S1) and matching the maximum of the AHP with drastic ecological conditions and maximum water stratification. During this period, the dominant warm taxon Globigerinoides ruber increased significantly in size and accumulation rate marking an opportunistic behavior and a total adaptation to the less saline and stratified waters. After 8.8 cal ka BP, the increase in diversity marked a progressive return to normal conditions; 4) from 6.4 to 2.9 cal ka BP, a progressive aridification period was recorded and the planktic ecosystem returned progressively to equilibrium conditions due to the recovery of thermohaline circulation after S1 and the decrease in Nile runoff; 5) from 2.9 to 1.1 cal ka BP, particular dry conditions were recorded leading to a severe drop in planktic diversity. These conditions seemed to be connected to a

  13. Adequate iodine levels in healthy pregnant women. A cross-sectional survey of dietary intake in Turkey

    PubMed Central

    Kasap, Burcu; Akbaba, Gülhan; Yeniçeri, Emine N.; Akın, Melike N.; Akbaba, Eren; Öner, Gökalp; Turhan, Nilgün Ö.; Duru, Mehmet E.

    2016-01-01

    Objectives: To assess current iodine levels and related factors among healthy pregnant women. Methods: In this cross-sectional, hospital-based study, healthy pregnant women (n=135) were scanned for thyroid volume, provided urine samples for urinary iodine concentration and completed a questionnaire including sociodemographic characteristics and dietary habits targeted for iodine consumption at the Department of Obstetrics and Gynecology, School of Medicine, Muğla Sıtkı Koçman University, Muğla, Turkey, between August 2014 and February 2015. Sociodemographic data were analyzed by simple descriptive statistics. Results: Median urinary iodine concentration was 222.0 µg/L, indicating adequate iodine intake during pregnancy. According to World Health Organization (WHO) criteria, 28.1% of subjects had iodine deficiency, 34.1% had adequate iodine intake, 34.8% had more than adequate iodine intake, and 3.0% had excessive iodine intake during pregnancy. Education level, higher monthly income, current employment, consuming iodized salt, and adding salt to food during, or after cooking were associated with higher urinary iodine concentration. Conclusion: Iodine status of healthy pregnant women was adequate, although the percentage of women with more than adequate iodine intake was higher than the reported literature. PMID:27279519

  14. BP, Cardiovascular Disease, and Death in the Folic Acid for Vascular Outcome Reduction in Transplantation Trial

    PubMed Central

    John, Alin; Weir, Matthew R.; Smith, Stephen R.; Hunsicker, Lawrence; Kasiske, Bertram L.; Kusek, John W.; Bostom, Andrew; Ivanova, Anastasia; Levey, Andrew S.; Solomon, Scott; Pesavento, Todd; Weiner, Daniel E.

    2014-01-01

    The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.1 years (25th to 75th percentiles, 1.7–7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels<70 mmHg, each 10-mmHg decrease in diastolic BP level associated with a 31% increase in CVD risk (HR, 1.31; 95% CI, 1.06 to 1.62) and a 31% increase in mortality risk (HR, 1.31; 95% CI, 1.03 to 1.66). However, at diastolic BP levels>70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial. PMID:24627349

  15. BP1, an Isoform of DLX4 Homeoprotein, Negatively Regulates BRCA1 in Sporadic Breast Cancer

    PubMed Central

    Kluk, Brian J.; Fu, Yebo; Formolo, Trina A.; Zhang, Lei; Hindle, Anne K.; Man, Yan-gao; Siegel, Robert S.; Berg, Patricia E.; Deng, Chuxia; McCaffrey, Timothy A.; Fu, Sidney W.

    2010-01-01

    Introduction: Several lines of evidence point to an important role for BP1, an isoform of DLX4 homeobox gene, in breast carcinogenesis and progression. BRCA1 is a well-known player in the etiology of breast cancer. While familial breast cancer is often marked by BRCA1 mutation and subsequent loss of heterozygosity, sporadic breast cancers exhibit reduced expression of wild type BRCA1, and loss of BRCA1 expression may result in tumor development and progression. Methods: The Cister algorithm and Genomatix program were used to identify potential BP1 binding sites in BRCA1 gene. Real-time PCR, Western blot and immunohistochemistry analysis were performed to verify the expression of BRCA1 and BP1 in cell lines and breast cancer tissues. Double-stranded siRNA transfection was carried out for silencing BP1 expression. ChIP and EMSA were used to confirm that BP1 specifically binds to BRCA1. Results: A putative BP1 binding site was identified in the first intron of BRCA1, which was confirmed by chromatin immunoprecipiation and electrophoresis mobility shift assay. BP1 and BRCA1 expression were inversely correlated in breast cancer cell lines and tissues, suggesting that BP1 may suppress BRCA1 transcription through consensus sequence binding. Conclusions: BP1 homeoprotein represses BRCA1 expression through direct binding to its first intron, which is consistent with a previous study which identified a novel transcriptional repressor element located more than 500 base pairs into the first intron of BRCA1, suggesting that the first intron plays an important role in the negative regulation of BRCA1. Although further functional studies are necessary to confirm its repressor activity towards BRCA1, the elucidation of the role of BP1 in breast tumorigenesis holds great promise in establishing BP1 as a novel target for drug therapy. PMID:20877436

  16. Epitope mapping of the Brucella melitensis BP26 immunogenic protein: usefulness for diagnosis of sheep brucellosis.

    PubMed

    Seco-Mediavilla, Patricia; Verger, Jean-Michel; Grayon, Maggy; Cloeckaert, Axel; Marín, Clara M; Zygmunt, Michel S; Fernández-Lago, Luis; Vizcaíno, Nieves

    2003-07-01

    Sequencing of bp26, the gene encoding the Brucella sp. immunogenic BP26 periplasmic protein, was performed in the reference strains of Brucella abortus, B. suis, and B. ovis. The three bp26 sequences were almost identical to that published for B. melitensis 16M bp26, and only minor nucleotide substitutions, without modifying the amino acid sequence, were observed between species. The bp26 genes of the seven B. abortus biovar reference strains and B. abortus S19 and RB51 vaccine strains were also sequenced. Again, only minor differences were found. Surprisingly, the bp26 nucleotide sequence for B. abortus S19 was almost identical to that found for B. melitensis 16M and differed from the sequence described previously by others (O. L. Rossetti, A. I. Arese, M. L. Boschiroli, and S. L. Cravero, J. Clin. Microbiol. 34:165-169, 1996) for the same B. abortus strain. The epitope mapping of BP26, performed by using a panel of monoclonal antibodies and recombinant DNA techniques, allowed the identification of an immunodominant region of the protein interesting for the diagnosis of B. melitensis and B. ovis infection in sheep. A recombinant fusion protein containing this region of BP26 reacted indeed, in Western blotting, as the entire recombinant BP26 against sera from B. melitensis- or B. ovis-infected sheep while it avoided false-positive reactions observed with sera from Brucella-free sheep when using the entire recombinant BP26. Thus, use of this recombinant fusion protein instead the entire recombinant BP26 could improve the specific serological diagnosis of B. melitensis or B. ovis infection in sheep.

  17. How to meet intersatellite links mission requirements by an adequate optical terminal design?

    NASA Astrophysics Data System (ADS)

    Duchmann, O.; Planche, G.

    1991-06-01

    The SILEX system involves a large set of advanced techniques and technologies which need to be merged and confronted. A macroscopic approach makes it possible to consider an optical terminal, with reference to common space fields of activities as a combination of a communication payload, an attitude and orbit control system, an optical instrument, and an on-board data handling system. It requires great technical expertise in areas commonly mastered in these techniques, namely, highly sensitive detectors such as coupled charge detector matrices, avalanche photodiodes, accurate and/or high bandwidth pointing and steering mechanisms, high optical quality mirrors and optical coatings, and accurate thermal control. Basic system and engineering tasks are to be mastered to combine them in an optimal way. This calls, among other things, for requirements analysis to derive the main design drivers and specific constraints with respect to each technique involved, and sizing and configuration of the system.

  18. The role of adequate reference materials in density measurements in hemodialysis

    NASA Astrophysics Data System (ADS)

    Furtado, A.; Moutinho, J.; Moura, S.; Oliveira, F.; Filipe, E.

    2015-02-01

    In hemodialysis, oscillation-type density meters are used to measure the density of the acid component of the dialysate solutions used in the treatment of kidney patients. An incorrect density determination of this solution used in hemodialysis treatments can cause several and adverse events to patients. Therefore, despite the Fresenius Medical Care (FME) tight control of the density meters calibration results, this study shows the benefits of mimic the matrix usually measured to produce suitable reference materials for the density meter calibrations.

  19. Juvenile idiopathic arthritis and athletic participation: are we adequately preparing for sports integration?

    PubMed

    Taxter, Alysha; Foss, Kim Barber; Melson, Paula; Ford, Kevin R; Shaffer, Michael; Myer, Gregory D

    2012-09-01

    Children with juvenile idiopathic arthritis (JIA) now have well-controlled disease due to improved therapies and management strategies. Children with JIA are more active than in the past and often participate in dynamic, high-loading sports. Standard measures of disease control include examination findings, laboratory values, and patient-directed surveys. However, these standards do not address the subtle deficits in biomechanics and neuromuscular control, which could place affected joints at higher risk for injury. Currently, there are limited evidence-based guidelines to structure conditioning recommendations as to the fitness and mechanics needed to provide safe integration into sports in this population; therefore, tools that objectively measure function with high accuracy and precision may be warranted. Previous work using 3-dimensional motion analysis demonstrated usefulness in guiding physical therapy treatment to correct these deficits. The use of a multidisciplinary team, including physical therapy, rheumatology, and sports medicine, is crucial for preparing these children to return to play. We suggest that the child transition into a sport preparatory-conditioning program to address any underlying deficits. A pediatric exercise specialist who is sensitive to the needs of this population can work with a physical therapist to then appropriately integrate the child safely into sport. Encouraging an active lifestyle is vital to the management of JIA and does not worsen the symptoms associated with childhood arthritis.

  20. The GYF domain protein CD2BP2 is critical for embryogenesis and podocyte function.

    PubMed

    Albert, Gesa I; Schell, Christoph; Kirschner, Karin M; Schäfer, Sebastian; Naumann, Ronald; Müller, Alexandra; Kretz, Oliver; Kuropka, Benno; Girbig, Mathias; Hübner, Norbert; Krause, Eberhard; Scholz, Holger; Huber, Tobias B; Knobeloch, Klaus-Peter; Freund, Christian

    2015-10-01

    Scaffolding proteins play pivotal roles in the assembly of macromolecular machines such as the spliceosome. The adaptor protein CD2BP2, originally identified as a binding partner of the adhesion molecule CD2, is a pre-spliceosomal assembly factor that utilizes its glycine-tyrosine-phenylalanine (GYF) domain to co-localize with spliceosomal proteins. So far, its function in vertebrates is unknown. Using conditional gene targeting in mice, we show that CD2BP2 is crucial for embryogenesis, leading to growth retardation, defects in vascularization, and premature death at embryonic day 10.5 when absent. Ablation of the protein in bone marrow-derived macrophages indicates that CD2BP2 is involved in the alternative splicing of mRNA transcripts from diverse origins. At the molecular level, we identified the phosphatase PP1 to be recruited to the spliceosome via the N-terminus of CD2BP2. Given the strong expression of CD2BP2 in podocytes of the kidney, we use selective depletion of CD2BP2, in combination with next-generation sequencing, to monitor changes in exon usage of genes critical for podocyte functions, including VEGF and actin regulators. CD2BP2-depleted podocytes display foot process effacement, and cause proteinuria and ultimately lethal kidney failure in mice. Collectively, our study defines CD2BP2 as a non-redundant splicing factor essential for embryonic development and podocyte integrity.

  1. Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation

    PubMed Central

    Panas, Marc D.; Schulte, Tim; Thaa, Bastian; Sandalova, Tatiana; Kedersha, Nancy; Achour, Adnane; McInerney, Gerald M.

    2015-01-01

    The Ras-GAP SH3 domain–binding proteins (G3BP) are essential regulators of the formation of stress granules (SG), cytosolic aggregates of proteins and RNA that are induced upon cellular stress, such as virus infection. Many viruses, including Semliki Forest virus (SFV), block SG induction by targeting G3BP. In this work, we demonstrate that the G3BP-binding motif of SFV nsP3 consists of two FGDF motifs, in which both phenylalanine and the glycine residue are essential for binding. In addition, we show that binding of the cellular G3BP-binding partner USP10 is also mediated by an FGDF motif. Overexpression of wt USP10, but not a mutant lacking the FGDF-motif, blocks SG assembly. Further, we identified FGDF-mediated G3BP binding site in herpes simplex virus (HSV) protein ICP8, and show that ICP8 binding to G3BP also inhibits SG formation, which is a novel function of HSV ICP8. We present a model of the three-dimensional structure of G3BP bound to an FGDF-containing peptide, likely representing a binding mode shared by many proteins to target G3BP. PMID:25658430

  2. Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

    SciTech Connect

    Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming . E-mail: fandaim@fmmu.edu.cn

    2007-05-18

    Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to {beta}-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing {beta}-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells.

  3. 76 FR 69713 - Application To Export Electric Energy; BP Energy Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... Application To Export Electric Energy; BP Energy Company AGENCY: Office of Electricity Delivery and Energy... its authority to transmit electric energy from the United States to Mexico pursuant to section 202(e... Order No. EA-314, which authorized BP Energy to transmit electric energy from the United States...

  4. 76 FR 69712 - Application To Export Electric Energy; BP Energy Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... Application To Export Electric Energy; BP Energy Company AGENCY: Office of Electricity Delivery and Energy... its authority to transmit electric energy from the United States to Canada pursuant to section 202(e... (DOE) issued Order No. EA-315, which authorized BP Energy to transmit electric energy from the...

  5. 53BP1 foci as a marker of tumor cell radiosensitivity.

    PubMed

    Markova, E; Vasilyev, S; Belyaev, I

    2015-01-01

    Predicting tumor radiosensitivity has yet to be routinely integrated into radiotherapy. We analyzed the possibility to assess radiosensitivity of tumor cells based on endogenous and radiation-induced 53BP1 foci which are molecular markers of DNA double strand breaks (DSB). In eleven tumor cell lines of different origin, radiosensitivity was assessed by surviving cell fraction following irradiation with 2 Gy (SF2). 53BP1 foci were measured at 4 and 12 h post-irradiation by confocal laser microscopy and dedicated software. The correlation of 53BP1 foci and their post-irradiation kinetics with SF2 was assessed using Spearman rank test. The SF2 correlated with both excess of radiation-induced 53BP1 foci per cell at 4 h after irradiation and decay in number of 53BP1 foci from 4 to 12 h post-irradiation. The fraction of cells with multiple endogenous 53BP1 foci also correlated with SF2 of tumor cells. We conclude that the radiosensitivity of tumor cells can be predicted by kinetics of formation and decay of 53BP1 foci after irradiation. For the first time we report that the fraction of cells with multiple endogenous 53BP1 foci can be used as a marker of tumor cell radiosensitivity. PMID:26278144

  6. Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation.

    PubMed

    Panas, Marc D; Schulte, Tim; Thaa, Bastian; Sandalova, Tatiana; Kedersha, Nancy; Achour, Adnane; McInerney, Gerald M

    2015-02-01

    The Ras-GAP SH3 domain-binding proteins (G3BP) are essential regulators of the formation of stress granules (SG), cytosolic aggregates of proteins and RNA that are induced upon cellular stress, such as virus infection. Many viruses, including Semliki Forest virus (SFV), block SG induction by targeting G3BP. In this work, we demonstrate that the G3BP-binding motif of SFV nsP3 consists of two FGDF motifs, in which both phenylalanine and the glycine residue are essential for binding. In addition, we show that binding of the cellular G3BP-binding partner USP10 is also mediated by an FGDF motif. Overexpression of wt USP10, but not a mutant lacking the FGDF-motif, blocks SG assembly. Further, we identified FGDF-mediated G3BP binding site in herpes simplex virus (HSV) protein ICP8, and show that ICP8 binding to G3BP also inhibits SG formation, which is a novel function of HSV ICP8. We present a model of the three-dimensional structure of G3BP bound to an FGDF-containing peptide, likely representing a binding mode shared by many proteins to target G3BP.

  7. 75 FR 68607 - BP Canada Energy Marketing Corp. Apache Corporation; Notice for Temporary Waivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission BP Canada Energy Marketing Corp. Apache Corporation; Notice for Temporary Waivers November 1, 2010. Take notice that on October 29, 2010, BP Canada Energy Marketing Corp....

  8. 75 FR 69652 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling AGENCY: Department of... meeting of the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling (the... associated with offshore drilling in the future. The Commission is composed of seven members appointed by...

  9. 75 FR 60097 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    ... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling AGENCY: Department of... meeting of the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling (the... associated with offshore drilling in the future. The Commission is composed of seven members appointed by...

  10. 75 FR 39518 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-09

    ..., 2010, of the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling, (75 FR... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling; Correction AGENCY: Office...: Christopher A. Smith, (202) 586-0716. Corrections In the Federal Register of June 30, 2010, in FR Doc....

  11. 75 FR 65309 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling AGENCY: Department of... meeting of the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling (the..., and mitigate the impact of, any oil spills associated with offshore drilling in the future....

  12. 75 FR 37783 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling AGENCY: Department of... meeting of the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling (the... offshore drilling in the future. The Commission is composed of seven members appointed by the President...

  13. 75 FR 56526 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling AGENCY: Department of... meeting of the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling (the... with offshore drilling in the future. The Commission is composed of seven members appointed by...

  14. 75 FR 47584 - National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling AGENCY: Department of... meeting for the National Commission on the BP Deepwater Horizon Oil Spill and Offshore Drilling (the..., and mitigate the impact of, any oil spills associated with offshore drilling in the future....

  15. Three not adequately understood lunar phenomena investigated by the wave planetology

    NASA Astrophysics Data System (ADS)

    Kochemasov, G. G.

    2009-04-01

    Three not adequately understood lunar phenomena investigated by the wave planetology G. Kochemasov IGEM of the Russian Academy of Sciences, Moscow, Russia, kochem.36@mail.ru The lunar science notwithstanding rather numerous researches of the last 50 years still debates some important issues. Three of them concern an origin of mascons, the deepest but low ferruginous South Pole-Aitken depression, a strange character of the frequency-crater size curve. Prevailing approaches are mainly based on impacts having made the present geomorphology of the Moon. However practically are ignored the fact of antipodality of basins and marea, a complex character of the frequency-crater size curve obviously implying an involvement of different sources and reasons responsible for crater formation. Attempts to find impactor sources in various sometimes very remote parts of the Solar system are too artificial, besides they do not explain very intensive, like lunar cratering of Mercury. Saturation of the lunar surface by ~70-km diameter craters is very strange for random impacts from any source; to find a time interval for this saturation is difficult if not possible because it affects formations of various ages. Lunar basins and marea completely contradict to a classical frequency- crater size curve. Their presumed ( and measured) different ages make dubious existence of one specialized impactor source. So, if one accepts an impact process as the only process responsible for cratering (ring forms development) then the real mess in crater statistics and timing never will be overcome. The wave planetology [1-3 & others] examined by many planets and satellites of the Solar system proved to be real. In a case of the Moon it can help in answering the above questions. First of all it should be admitted that the complex lunar crater (ring forms) statistics is due to a superposition and mixing of two main processes (a minor involvement of volcanic features is also present): impacts and wave

  16. Three not adequately understood lunar phenomena investigated by the wave planetology

    NASA Astrophysics Data System (ADS)

    Kochemasov, G. G.

    2009-04-01

    Three not adequately understood lunar phenomena investigated by the wave planetology G. Kochemasov IGEM of the Russian Academy of Sciences, Moscow, Russia, kochem.36@mail.ru The lunar science notwithstanding rather numerous researches of the last 50 years still debates some important issues. Three of them concern an origin of mascons, the deepest but low ferruginous South Pole-Aitken depression, a strange character of the frequency-crater size curve. Prevailing approaches are mainly based on impacts having made the present geomorphology of the Moon. However practically are ignored the fact of antipodality of basins and marea, a complex character of the frequency-crater size curve obviously implying an involvement of different sources and reasons responsible for crater formation. Attempts to find impactor sources in various sometimes very remote parts of the Solar system are too artificial, besides they do not explain very intensive, like lunar cratering of Mercury. Saturation of the lunar surface by ~70-km diameter craters is very strange for random impacts from any source; to find a time interval for this saturation is difficult if not possible because it affects formations of various ages. Lunar basins and marea completely contradict to a classical frequency- crater size curve. Their presumed ( and measured) different ages make dubious existence of one specialized impactor source. So, if one accepts an impact process as the only process responsible for cratering (ring forms development) then the real mess in crater statistics and timing never will be overcome. The wave planetology [1-3 & others] examined by many planets and satellites of the Solar system proved to be real. In a case of the Moon it can help in answering the above questions. First of all it should be admitted that the complex lunar crater (ring forms) statistics is due to a superposition and mixing of two main processes (a minor involvement of volcanic features is also present): impacts and wave

  17. Direct observation of a 91 bp LacI-mediated, negatively supercoiled DNA loop by atomic force microscope.

    PubMed

    Fulcrand, Geraldine; Chapagain, Prem; Dunlap, David; Leng, Fenfei

    2016-03-01

    Escherichia coli lactose repressor (LacI), a tetrameric protein, is a paradigmatic transcriptional factor that controls the expression of lacZYA in the lac operon. It specifically binds to the O1, O2, and O3 operators of the lac promoter, forms DNA loops, and regulates transcription of the lac operon. In this article, utilizing combined techniques of DNA-nicking assay and AFM imaging, we directly observed a 91 bp LacI-mediated, negatively supercoiled DNA loop mimicking the DNA loop between the O1 and O3 operators in the lac promoter. PMID:26878689

  18. Association between a Functional HLA-G 14-bp Insertion/deletion Polymorphism and Susceptibility to Autoimmune Diseases: A Meta-analysis.

    PubMed

    Lee, Y H; Bae, S-C

    2015-12-09

    The aim of this study was to determine whether a functional human leukocyte antigen-G (HLA-G) 14-bp insertion (I)/deletion (D) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted to assess the association between an HLA-G 14-bp I/D polymorphism and autoimmune diseases using 1) allele contrast, as well as 2) recessive, 3) dominant, and 4) codominant models. Sixteen articles that included 20 comparative studies with 3,555 patients and 5,225 controls were included in the meta-analysis. These studies were performed on nine Caucasian, six South American, three Asian, one Arab, and one African population samples. Our meta-analysis revealed no association between autoimmune diseases and the HLA-G 14-bp I/D polymorphism [odds ratio (OR) for allele I = 1.055; 95% confidence interval (CI) = 0.963-1.156; p = 0.251)]. However, meta-analysis according to autoimmune disease type revealed an association between systemic lupus erythematosus (SLE) and the II+ID genotype of the HLA-G 14-bp I/D polymorphism (OR = 1.205; 95% CI = 1.036-1.403; p = 0.016). Furthermore, analysis using a codominant model revealed an association between this polymorphism and SLE (OR for ID vs. DD = 1.203; 95% CI = 1.024-1.413; p = 0.024). In contrast, our meta-analysis revealed no association between rheumatoid arthritis (RA), multiple sclerosis (MS), or Crohn's disease (CD) and the HLA-G 14-bp I/D polymorphism. This meta-analysis showed that the HLA-G 14-bp I/D polymorphism is associated with susceptibility to a subgroup of autoimmune diseases such as SLE, but not RA, MS, or CD. These results support the existence of an association between the HLA-G gene and a subgroup of autoimmune diseases.

  19. Meta-analysis of the human leukocyte antigen-G (HLA-G) 14 bp insertion/deletion polymorphism as a risk factor for preeclampsia.

    PubMed

    Pabalan, N; Jarjanazi, H; Sun, C; Iversen, A C

    2015-09-01

    The non-classical major histocompatibility complex, human leukocyte antigen (HLA)-G, plays an important role in pregnancy. HLA-G mediates proper interaction between maternal immune cells and fetal trophoblasts invading the uterine wall, to ensure successful placental development and function. Several HLA-G gene variants have been shown to be associated with development of preeclampsia (PE), but the reported associations of the HLA-G 14 base pair (bp) insertion/deletion (I/D) polymorphism (rs66554220) with PE are inconsistent. In this meta-analysis of HLA-G 14 bp I/D in each member of the family triad, we estimated risk (odds ratio [OR], 95% confidence interval) of associations with PE based on nine published offspring, nine mother and three father case-control studies. No significant increased risk associations between PE and HLA-G 14 bp I/D were detected in any of the family triad members (offspring: OR = 1.08-1.21, P = 0.57-0.74; mothers: OR = 1.11-1.28, P = 0.07-0.44; fathers: OR = 1.09-1.65, P = 0.07-0.70). Of the 20 comparisons performed, 14 (70%) were non-heterogeneous and seven of these had zero heterogeneity (I(2) = 0%). Sensitivity treatment confirmed robustness for the overall lack of association for HLA-G 14 bp I/D. In subgroup analysis, significant association between HLA-G 14 bp I/D and PE was shown in offspring from primipara (OR = 1.66-1.95, P = 0.04) and European Caucasian pregnancies (OR = 1.37-2.03, P = 0.02-0.03). However, heterogeneity and sensitivity tests suggest that further investigation is needed to determine if HLA-G 14 bp I/D is involved in trophoblast HLA-G expression and PE development in these subgroups.

  20. Centennial and millennial-scale hydroclimate changes in northwestern Patagonia since 16,000 yr BP

    NASA Astrophysics Data System (ADS)

    Moreno, Patricio I.; Videla, Javiera

    2016-10-01

    We examine hydroclimate changes at centennial/millennial timescales since 16,000 yr BP in northwestern Patagonia based on the pollen and charcoal record from Lago El Salto, a small closed-basin lake located in the Chilean Lake District (41°38‧48.02″S, 73° 5‧48.42″W). We observe cold/wet conditions between 14,500-16,000 yr BP, followed by further cooling with increased precipitation until 13,000 yr BP, enhanced precipitation seasonality and/or variability between 11,600-13,000 yr BP, and an extended warm-and-dry interval between 7600 and 11,300 yr BP with peak paleofire activity. Colder-and-wetter than present conditions and muted paleofire activity prevail between 5300 and 7600 yr BP, followed by alternating cold/wet and centennial-scale warm/dry phases starting at 5300 yr BP with three conspicuous megadroughts since 2500 yr BP. The most recent megadrought occurred during the Medieval Climate Anomaly. We identify a cold reversal that spans the Antarctic Cold Reversal (ACR) and the Younger Dryas (YD) chrons with stronger-than-present westerly influence during the former and enhanced variability during the latter. These results extend the northern limit of strong cooling and increase in precipitation during the ACR and the southern limit of influence of strong hydrologic variations during the YD in terrestrial environments, suggesting an overlap in the spheres of influence of processes originating from southern and northern polar latitudes. An extended warm southern westerly wind (SWW)-minimum interval is evident between 7600 and 11,300 yr BP, followed by a rapid shift to cool-moist conditions between 5300 and 7600 yr BP brought by a mid-Holocene SWW maximum. Since then we observe centennial-scale hydroclimate variability, which has driven biodiversity and fire-regime shifts of evergreen temperate rainforests.

  1. Benzo[a]pyrene (BP) DNA adduct formation in DNA repair–deficient p53 haploinsufficient [Xpa(−/−)p53(+/−)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days

    PubMed Central

    Poirier, Miriam C.

    2012-01-01

    We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(−/−)p53(+/−) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N 2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)–DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(−/−)p53(+/−) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(−/−)p53(+/−) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(−/−)p53(+/−) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP–DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(−/−)p53(+/−) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH–DNA adduct levels consistently in human organs. PMID:22828138

  2. A 63bp deletion in the promoter of rage correlates with a decreased risk for nephropathy in patients with type 2 diabetes.

    PubMed

    Rudofsky, G; Isermann, B; Schilling, T; Schiekofer, S; Andrassy, M; Schneider, J G; Morcos, M; Humpert, P M; Sayed, A A R; Witte, S; Renn, W; Pfohl, M; Hamann, A; Nosikov, V; Schleicher, E; Häring, H-U; Rudofsky, G; Ritz, E; Nawroth, P P; Bierhaus, A

    2004-03-01

    Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.

  3. Evaluation of the Association of IGF2BP2 Variants With Type 2 Diabetes in French Caucasians

    PubMed Central

    Duesing, Konsta; Fatemifar, Ghazaleh; Charpentier, Guillaume; Marre, Michel; Tichet, Jean; Hercberg, Serge; Balkau, Beverley; Froguel, Philippe; Gibson, Fernando

    2008-01-01

    OBJECTIVE—We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus in order to replicate the association of the “confirmed” type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population and to further characterize the susceptibility variants at this novel locus. RESEARCH DESIGN AND METHODS—We genotyped a total of 21 tagging single nucleotide polymorphisms spanning the IGF2BP2 locus in our type 2 diabetes case-control cohort comprising 3,093 French Caucasian subjects. RESULTS—IGF2BP2 variants rs4402960 and rs1470579 were not associated with type 2 diabetes in the present study (P = 0.632 and P = 0.896, respectively). Meta-analysis of genotype data from over 34,000 subjects demonstrated that our inability to replicate rs4402960/rs1470579 was consistent with the findings from several previous genome-wide association study (GWAS) datasets that were underpowered to detect this modest association signal (odds ratio [OR] 1.14). We obtained novel evidence that rs9826022, a borderline rare variant (5% minor allele frequency) in the 3′ downstream region, was associated with type 2 diabetes (P = 0.0002; OR 1.53 [95% CI 1.22–1.91]). This result was corroborated by the meta-analysis of 10,542 genotypes from the current study and GWAS datasets using both fixed (P = 9.47 × 10−6; 1.30 [1.16–1.46]) and random effects (P = 0.001; 1.30 [1.11–1.52)] calculations. CONCLUSIONS—We were unable to replicate the confirmed rs4402960/rs1470579 susceptibility variants but found novel evidence for a rare variant in the 3′ downstream region of IGF2BP2. Further genetic and functional studies are required to identify the etiological IGF2BP2 variants. PMID:18430866

  4. Wasted (wst) mice have 3-bp deletion in the PCNA promoter

    SciTech Connect

    Paunesku, T.; Woloschak, G.E.

    1997-08-01

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. Previous results from the authors` group have shown that (1) wasted mice have little if any detectable PCNA protein or mRNA in thymus, but levels in liver, brain, and other tissues are similar to those in controls; and (2) the coding region for PCNA is the same in wasted mice and in control littermates. These observations gave rise to the present study, in which the PCNA promoter was sequenced for wst/wst mice, control littermates ({center_dot}wst/+) and BCF{sub 1} (or BALB/c x C57BL/6) F{sub 1} controls. Sequence analysis revealed only one difference between wst/wst and BALB/c x C57BL/6 F{sub 1} littermates: a 3-bp deletion in the 5 foot upstream region of the PCNA gene of wasted mice that was observed on only one allele or no alleles of normal littermates. The mutated sites in PCNA promoter from two litters plus two additional wst/wst and two known wst/+ animals were screened with 8G and 11G probes, and each confirmed this pattern. The short term DNA segment encompassing the deletion was shown in gel shift experiments to bind a nuclear protein(s) present in a broad variety of cells including thymus and spleen nuclear extract from wst/wst and control mice. The mutated oligomer that was homozygous only in wst/wst mice was not able to bind the same nuclear protein(s).

  5. 21 CFR 1.283 - What happens to food that is imported or offered for import without adequate prior notice?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What happens to food that is imported or offered for import without adequate prior notice? 1.283 Section 1.283 Food and Drugs FOOD AND DRUG... Imported Food Consequences § 1.283 What happens to food that is imported or offered for import...

  6. 21 CFR 1.283 - What happens to food that is imported or offered for import without adequate prior notice?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What happens to food that is imported or offered for import without adequate prior notice? 1.283 Section 1.283 Food and Drugs FOOD AND DRUG... Imported Food Consequences § 1.283 What happens to food that is imported or offered for import...

  7. 23 CFR 669.13 - Effect of failure to certify or to adequately obtain proof-of-payment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Effect of failure to certify or to adequately obtain proof-of-payment. 669.13 Section 669.13 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS ENFORCEMENT OF HEAVY VEHICLE USE TAX § 669.13 Effect of...

  8. 45 CFR 2508.10 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... maintained in a secured room with a locking door. (3) Access to and use of a system of records shall be...) Access to areas where a system of records is stored will be limited to those persons whose duties require... require access to and use of records contained in a system of records are adequately trained to...

  9. 45 CFR 2508.10 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... maintained in a secured room with a locking door. (3) Access to and use of a system of records shall be...) Access to areas where a system of records is stored will be limited to those persons whose duties require... require access to and use of records contained in a system of records are adequately trained to...

  10. 45 CFR 2508.10 - Who has the responsibility for maintaining adequate technical, physical, and security safeguards...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... maintained in a secured room with a locking door. (3) Access to and use of a system of records shall be...) Access to areas where a system of records is stored will be limited to those persons whose duties require... require access to and use of records contained in a system of records are adequately trained to...

  11. Adequate Funding of Education Programs for At-Risk Children: An Econometric Application of Research-Based Cost Differentials

    ERIC Educational Resources Information Center

    Alexander, Kern; Wall, Andrew

    2006-01-01

    This article contributes to the ongoing discussion of the adequacy of funding for public schools, specifically with regard to the provision of programs for at-risk children. Of particular concern is the determination of realistic, research-based costs of adequately funded programs. This article has three basic parts: the definition and measurement…

  12. Iodine Status of Women of Reproductive Age in Sierra Leone and Its Association with Household Coverage with Adequately Iodized Salt.

    PubMed

    Rohner, Fabian; Wirth, James P; Woodruff, Bradley A; Chiwile, Faraja; Yankson, Hannah; Sesay, Fatmata; Koroma, Aminata S; Petry, Nicolai; Pyne-Bailey, Solade; Dominguez, Elisa; Kupka, Roland; Hodges, Mary H; de Onis, Mercedes

    2016-02-01

    Salt iodization programs are a public health success in tackling iodine deficiency. Yet, a large proportion of the world's population remains at risk for iodine deficiency. In a nationally representative cross-sectional survey in Sierra Leone, household salt samples and women's urine samples were quantitatively analyzed for iodine content. Salt was collected from 1123 households, and urine samples from 817 non-pregnant and 154 pregnant women. Household coverage with adequately iodized salt (≥15 mg/kg iodine) was 80.7%. The median urinary iodine concentration (UIC) of pregnant women was 175.8 µg/L and of non-pregnant women 190.8 µg/L. Women living in households with adequately iodized salt had higher median UIC (for pregnant women: 180.6 µg/L vs. 100.8 µg/L, respectively, p < 0.05; and for non-pregnant women: 211.3 µg/L vs. 97.8 µg/L, p < 0.001). Differences in UIC by residence, region, household wealth, and women's education were much smaller in women living in households with adequately iodized salt than in households without. Despite the high household coverage of iodized salt in Sierra Leone, it is important to reach the 20% of households not consuming adequately iodized salt. Salt iodization has the potential for increasing equity in iodine status even with the persistence of other risk factors for deficiency. PMID:26848685

  13. Update with 2009-10 Data and Five-Year Trends: How Many Schools Have Not Made Adequate Yearly Progress?

    ERIC Educational Resources Information Center

    Usher, Alexandra

    2011-01-01

    Recently, much attention has focused on the number of schools in the nation failing to make adequate yearly progress (AYP) in raising student achievement under the No Child Left Behind Act (NCLB). The Obama Administration has projected a dramatic increase in this number as 2014--the year when 100% of students are expected to score proficient on…

  14. DOD Overseas Schools: Compensation Adequate for Recruiting and Retaining Well-Qualified Teachers. Report to Congressional Requesters.

    ERIC Educational Resources Information Center

    Shaul, Marnie S.

    The National Defense Authorization Act for Fiscal Year 2002 directed the U.S. General Accounting Office to determine whether the Department of Defense (DOD) overseas teachers' compensation package is adequate to recruit and retain qualified teachers. The Act also required GAO to determine whether or not any revisions to the law governing DOD…

  15. Cognitive Attributes, Attention, and Self-Efficacy of Adequate and Inadequate Responders in a Fourth Grade Reading Intervention

    ERIC Educational Resources Information Center

    Cho, Eunsoo; Roberts, Garrett J.; Capin, Philip; Roberts, Greg; Miciak, Jeremy; Vaughn, Sharon

    2015-01-01

    We examined cognitive attributes, attention, and self-efficacy of fourth grade struggling readers who were identified as adequate responders (n = 27), inadequate responders with comprehension only deficits (n = 46), and inadequate responders with comprehension and word reading deficits (n = 52) after receiving a multicomponent reading…

  16. Using Fuzzy Logic to Identify Schools Which May Be Misclassified by the No Child Left Behind Adequate Yearly Progress Policy

    ERIC Educational Resources Information Center

    Yates, Donald W.

    2009-01-01

    This investigation developed, tested, and prototyped a Fuzzy Inference System (FIS) that would assist decision makers in identifying schools that may have been misclassified by existing Adequate Yearly Progress (AYP) methods. This prototype was then used to evaluate Louisiana elementary schools using published school data for Academic Year 2004. …

  17. Iodine Status of Women of Reproductive Age in Sierra Leone and Its Association with Household Coverage with Adequately Iodized Salt

    PubMed Central

    Rohner, Fabian; Wirth, James P.; Woodruff, Bradley A.; Chiwile, Faraja; Yankson, Hannah; Sesay, Fatmata; Koroma, Aminata S.; Petry, Nicolai; Pyne-Bailey, Solade; Dominguez, Elisa; Kupka, Roland; Hodges, Mary H.; de Onis, Mercedes

    2016-01-01

    Salt iodization programs are a public health success in tackling iodine deficiency. Yet, a large proportion of the world’s population remains at risk for iodine deficiency. In a nationally representative cross-sectional survey in Sierra Leone, household salt samples and women’s urine samples were quantitatively analyzed for iodine content. Salt was collected from 1123 households, and urine samples from 817 non-pregnant and 154 pregnant women. Household coverage with adequately iodized salt (≥15 mg/kg iodine) was 80.7%. The median urinary iodine concentration (UIC) of pregnant women was 175.8 µg/L and of non-pregnant women 190.8 µg/L. Women living in households with adequately iodized salt had higher median UIC (for pregnant women: 180.6 µg/L vs. 100.8 µg/L, respectively, p < 0.05; and for non-pregnant women: 211.3 µg/L vs. 97.8 µg/L, p < 0.001). Differences in UIC by residence, region, household wealth, and women’s education were much smaller in women living in households with adequately iodized salt than in households without. Despite the high household coverage of iodized salt in Sierra Leone, it is important to reach the 20% of households not consuming adequately iodized salt. Salt iodization has the potential for increasing equity in iodine status even with the persistence of other risk factors for deficiency. PMID:26848685

  18. Iodine Status of Women of Reproductive Age in Sierra Leone and Its Association with Household Coverage with Adequately Iodized Salt.

    PubMed

    Rohner, Fabian; Wirth, James P; Woodruff, Bradley A; Chiwile, Faraja; Yankson, Hannah; Sesay, Fatmata; Koroma, Aminata S; Petry, Nicolai; Pyne-Bailey, Solade; Dominguez, Elisa; Kupka, Roland; Hodges, Mary H; de Onis, Mercedes

    2016-02-03

    Salt iodization programs are a public health success in tackling iodine deficiency. Yet, a large proportion of the world's population remains at risk for iodine deficiency. In a nationally representative cross-sectional survey in Sierra Leone, household salt samples and women's urine samples were quantitatively analyzed for iodine content. Salt was collected from 1123 households, and urine samples from 817 non-pregnant and 154 pregnant women. Household coverage with adequately iodized salt (≥15 mg/kg iodine) was 80.7%. The median urinary iodine concentration (UIC) of pregnant women was 175.8 µg/L and of non-pregnant women 190.8 µg/L. Women living in households with adequately iodized salt had higher median UIC (for pregnant women: 180.6 µg/L vs. 100.8 µg/L, respectively, p < 0.05; and for non-pregnant women: 211.3 µg/L vs. 97.8 µg/L, p < 0.001). Differences in UIC by residence, region, household wealth, and women's education were much smaller in women living in households with adequately iodized salt than in households without. Despite the high household coverage of iodized salt in Sierra Leone, it is important to reach the 20% of households not consuming adequately iodized salt. Salt iodization has the potential for increasing equity in iodine status even with the persistence of other risk factors for deficiency.

  19. Understanding Unresponsiveness to Tier 2 Reading Intervention: Exploring the Classification and Profiles of Adequate and Inadequate Responders in First Grade

    ERIC Educational Resources Information Center

    Toste, Jessica R.; Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Gilbert, Jennifer K.; Cho, Eunsoo; Barquero, Laura A.; Bouton, Bobette D.

    2014-01-01

    The purpose of the current study was to examine academic and cognitive profiles of first graders who responded adequately and inadequately to intensive small-group reading intervention (Tier 2), as well as assess how these profiles differ based on the criteria used for classification of unresponsiveness. Nonresponders were identified using two…

  20. The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role

    PubMed Central

    RAFIGHDOOST, Firoozeh; RAFIGHDOOST, Amir; RAFIGHDOOST, Houshang; RIGI-LADEZ, Mohammad-Ayoob; HASHEMI, Mohammad; ESKANDARI-NASAB, Ebrahim

    2015-01-01

    Objective Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population. Material and Methods The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method. Results We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P. Conclusions Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects. PMID:26221921

  1. Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic Patients with Hypertension: The COAT Randomized Controlled Trial

    PubMed Central

    Takihata, Masahiro; Nakamura, Akinobu; Kondo, Yoshinobu; Kawasaki, Satsuki; Kimura, Mari; Terauchi, Yasuo

    2015-01-01

    Objective This study compared the efficacy and safety of azelnidipine with that of trichlormethiazide in Japanese type 2 diabetic patients with hypertension. Methods In a multicenter, open-label trial, 240 patients with adequately controlled diabetes (HbA1c ≤ 7.0%) under lifestyle modification and/or administration of hypoglycemic agents and inadequately controlled hypertension (systolic blood pressure [sBP] ≥ 130 mmHg or diastolic blood pressure [dBP] ≥ 80 mmHg) who were being treated with olmesartan were enrolled. Participants were randomly assigned to an azelnidipine group or a trichlormethiazide group and were followed up for 48 weeks. Main outcome measure was the difference in the change in HbA1c levels from the baseline values at 48 weeks between these two groups. Results Of the 240 subjects that were enrolled, 209 subjects (azelnidipine group: 103 patients, trichlormethiazide group: 106 patients) completed this trial. At 48 weeks, the following changes were observed in the azelnidipine and trichlormethiazide groups, respectively: HbA1c levels, 0.19 ± 0.52% and 0.19 ± 0.54%; sBP/dBP, -10.7 ± 9.6/-6.6 ± 6.6 mmHg and -7.1 ± 7.7/-3.3 ± 6.1 mmHg (P < 0.001 for both sBP and dBP). In both groups, dizziness (12 patients [11.7%] and 16 patients [15.1%]) and edema (16 patients [15.5%] and 7 patients [6.6%], P = 0.047) were observed during the 48-week follow-up period. Conclusions Azelnidipine was more effective for controlling blood pressure than trichlormethiazide in Japanese type 2 diabetes patients, whereas trichlormethiazide was more effective for reducing albuminuria than azelnidipine. Both of these agents, however, similarly exacerbated glycemic control in type 2 diabetic patients with hypertension. Trial Registration UMIN 000006081. PMID:25938807

  2. Characterization of a cancer cell line that expresses a splicing variant form of 53BP1: Separation of checkpoint and repair functions in 53BP1

    SciTech Connect

    Iwabuchi, Kuniyoshi Matsui, Tadashi; Hashimoto, Mitsumasa; Matsumoto, Yoshihisa; Kurihara, Takayuki; Date, Takayasu

    2008-11-21

    53BP1 plays important roles in checkpoint signaling and repair for DNA double-strand breaks. We found that a colon cancer cell line, SW48, expressed a splicing variant form of 53BP1, which lacks the residues corresponding to exons 10 and 11. Activation of ATM and phosphorylation of ATM and ATR targets occurred in SW48 cells in response to X-irradiation, and these X-ray-induced responses were not enhanced by expression of full-length 53BP1 in SW48 cells, indicating that this splicing variant fully activates the major checkpoint signaling in SW48 cells. In contrast, the expression of full-length 53BP1 in SW48 cells promoted the repair of X-ray-induced DNA damage, evidenced by faster disappearance of X-ray-induced {gamma}-H2AX foci, a marker for DNA damage, and less residual chromosomal aberrations after X-irradiation. We conclude that the two major roles of 53BP1, the checkpoint signaling and repair for DNA damage, can be functionally separated.

  3. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance

    PubMed Central

    Lindkær-Jensen, Steen; Larsen, Stig; Habib-Lindkær-Jensen, Nina; Fagertun, Hans E

    2015-01-01

    A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II) dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life. Methods The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose–response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design. Results Hemoglobin (Hb) and hematocrit (Hct) increased significantly (P<0.01) during BP-C1 treatment, while red blood cell (RBC) count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC) was in anemic patients (P≤0.01). WBC count and neutrophils increased significantly (P=0.01) in the overall data. WBCs and neutrophils (P<0.01), eosinophils (P=0.05) and monocytes (P<0.01) increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04). An increase in K+, Ca2+, and PO43− was most pronounced in patients with low baseline levels (P≤0.02). A similar pattern detected for Mg2+, prothrombin time (PT), coagulation factors II, VII, X (KFNT), and C-reactive protein (CRP), which increased significantly (P≤0.05) in the groups with the lowest values. Conclusion Our findings support the safety profile of BP-C1 use in cancer patients. BP-C1 did not induce anemia, infection, bleeding, hepatic insufficiency or electrolyte imbalances. In

  4. Adopting adequate leaching requirement for practical response models of basil to salinity

    NASA Astrophysics Data System (ADS)

    Babazadeh, Hossein; Tabrizi, Mahdi Sarai; Darvishi, Hossein Hassanpour

    2016-07-01

    Several mathematical models are being used for assessing plant response to salinity of the root zone. Objectives of this study included quantifying the yield salinity threshold value of basil plants to irrigation water salinity and investigating the possibilities of using irrigation water salinity instead of saturated extract salinity in the available mathematical models for estimating yield. To achieve the above objectives, an extensive greenhouse experiment was conducted with 13 irrigation water salinity levels, namely 1.175 dS m-1 (control treatment) and 1.8 to 10 dS m-1. The result indicated that, among these models, the modified discount model (one of the most famous root water uptake model which is based on statistics) produced more accurate results in simulating the basil yield reduction function using irrigation water salinities. Overall the statistical model of Steppuhn et al. on the modified discount model and the math-empirical model of van Genuchten and Hoffman provided the best results. In general, all of the statistical models produced very similar results and their results were better than math-empirical models. It was also concluded that if enough leaching was present, there was no significant difference between the soil salinity saturated extract models and the models using irrigation water salinity.

  5. [Adequate application of quantitative and qualitative statistic analytic methods in acupuncture clinical trials].

    PubMed

    Tan, Ming T; Liu, Jian-ping; Lao, Lixing

    2012-08-01

    Recently, proper use of the statistical methods in traditional Chinese medicine (TCM) randomized controlled trials (RCTs) has received increased attention. Statistical inference based on hypothesis testing is the foundation of clinical trials and evidence-based medicine. In this article, the authors described the methodological differences between literature published in Chinese and Western journals in the design and analysis of acupuncture RCTs and the application of basic statistical principles. In China, qualitative analysis method has been widely used in acupuncture and TCM clinical trials, while the between-group quantitative analysis methods on clinical symptom scores are commonly used in the West. The evidence for and against these analytical differences were discussed based on the data of RCTs assessing acupuncture for pain relief. The authors concluded that although both methods have their unique advantages, quantitative analysis should be used as the primary analysis while qualitative analysis can be a secondary criterion for analysis. The purpose of this paper is to inspire further discussion of such special issues in clinical research design and thus contribute to the increased scientific rigor of TCM research.

  6. M2BP inhibits HIV-1 virion production in a vimentin filaments-dependent manner

    PubMed Central

    Wang, Qin; Zhang, Xiaolin; Han, Yuling; Wang, Xinlu; Gao, Guangxia

    2016-01-01

    M2BP (also called 90K) is an interferon-stimulated gene product that is upregulated in HIV-1 infection. A recent study revealed that M2BP reduces the infectivity of HIV-1 by inhibiting the processing of the viral envelope protein. Here we report that in addition to reducing viral infectivity, M2BP inhibits HIV-1 virion production. We provide evidence showing that M2BP inhibits HIV-1 Gag trafficking to the plasma membrane in a vimentin-dependent manner. When vimentin filaments were collapsed by treating cells with acrylamide or by overexpression of a dominant-negative mutant of vimentin, M2BP inhibition of HIV-1 virion production was significantly relieved. We further show that M2BP interacts with both HIV-1 Gag and vimentin and thereby mediates their interactions. We propose that M2BP traps HIV-1 Gag to vimentin filaments to inhibit the transportation of HIV-1 Gag to the plasma membrane. These findings uncover a novel mechanism by which a host antiviral factor inhibits HIV-1 virion production. PMID:27604950

  7. M2BP inhibits HIV-1 virion production in a vimentin filaments-dependent manner.

    PubMed

    Wang, Qin; Zhang, Xiaolin; Han, Yuling; Wang, Xinlu; Gao, Guangxia

    2016-01-01

    M2BP (also called 90K) is an interferon-stimulated gene product that is upregulated in HIV-1 infection. A recent study revealed that M2BP reduces the infectivity of HIV-1 by inhibiting the processing of the viral envelope protein. Here we report that in addition to reducing viral infectivity, M2BP inhibits HIV-1 virion production. We provide evidence showing that M2BP inhibits HIV-1 Gag trafficking to the plasma membrane in a vimentin-dependent manner. When vimentin filaments were collapsed by treating cells with acrylamide or by overexpression of a dominant-negative mutant of vimentin, M2BP inhibition of HIV-1 virion production was significantly relieved. We further show that M2BP interacts with both HIV-1 Gag and vimentin and thereby mediates their interactions. We propose that M2BP traps HIV-1 Gag to vimentin filaments to inhibit the transportation of HIV-1 Gag to the plasma membrane. These findings uncover a novel mechanism by which a host antiviral factor inhibits HIV-1 virion production. PMID:27604950

  8. Role of CtBP2 in the Apoptosis of Retinal Ganglion Cells.

    PubMed

    Wang, Wenwen; Zhang, Guowei; Gu, Hui; Liu, Ye; Lao, Jifeng; Li, Kuifang; Guan, Huaijin

    2015-07-01

    Glaucoma damages the optic nerve and is a leading cause of irreversible blindness, and its pathogenesis remains unclear. C-terminal-binding protein 2 (CtBP2) is a transcriptional repressor which plays an important role in central nervous system injury and repair. Using the glaucoma model of DBA/2J mouse whose retina ganglion cells (RGCs) were degenerating with the process of glaucoma, we demonstrated for the first time the special relationship between CtBP2 protein and RGCs. Our research indicated that the expression of CtBP2 was gradually decreased with aging by the means of Western blotting. The CtBP2 immunoreactivity-positive cells were present in the various retinal layers, and CtBP2-positive cells were dramatically decreased in ganglion cell layer. Our research also found ectopic expression of CtBP2 can protect the apoptosis of primary mouse RGC cells induced by L-glutamate. These results suggest that CtBP2 may have a potential therapeutic effect in protecting RGC.

  9. Divergent homologs of the predicted small RNA BpCand697 in Burkholderia spp.

    NASA Astrophysics Data System (ADS)

    Damiri, Nadzirah; Mohd-Padil, Hirzahida; Firdaus-Raih, Mohd

    2015-09-01

    The small RNA (sRNA) gene candidate, BpCand697 was previously reported to be unique to Burkholderia spp. and is encoded at 3' non-coding region of a putative AraC family transcription regulator gene. This study demonstrates the conservation of BpCand697 sequence across 32 Burkholderia spp. including B. pseudomallei, B. mallei, B. thailandensis and Burkholderia sp. by integrating both sequence homology and secondary structural analyses of BpCand697 within the dataset. The divergent sequence of BpCand697 was also used as a discriminatory power in clustering the dataset according to the potential virulence of Burkholderia spp., showing that B. thailandensis was clearly secluded from the virulent cluster of B. pseudomallei and B. mallei. Finally, the differential co-transcript expression of BpCand697 and its flanking gene, bpsl2391 was detected in Burkholderia pseudomallei D286 after grown under two different culture conditions using nutrient-rich and minimal media. It is hypothesized that the differential expression of BpCand697-bpsl2391 co-transcript between the two standard prepared media might correlate with nutrient availability in the culture media, suggesting that the physical co-localization of BpCand697 in B. pseudomallei D286 might be directly or indirectly involved with the transcript regulation of bpsl2391 under the selected in vitro culture conditions.

  10. Establishing a Dynamic Self-Adaptation Learning Algorithm of the BP Neural Network and Its Applications

    NASA Astrophysics Data System (ADS)

    Li, Xiaofeng; Xiang, Suying; Zhu, Pengfei; Wu, Min

    2015-12-01

    In order to avoid the inherent deficiencies of the traditional BP neural network, such as slow convergence speed, that easily leading to local minima, poor generalization ability and difficulty in determining the network structure, the dynamic self-adaptive learning algorithm of the BP neural network is put forward to improve the function of the BP neural network. The new algorithm combines the merit of principal component analysis, particle swarm optimization, correlation analysis and self-adaptive model, hence can effectively solve the problems of selecting structural parameters, initial connection weights and thresholds and learning rates of the BP neural network. This new algorithm not only reduces the human intervention, optimizes the topological structures of BP neural networks and improves the network generalization ability, but also accelerates the convergence speed of a network, avoids trapping into local minima, and enhances network adaptation ability and prediction ability. The dynamic self-adaptive learning algorithm of the BP neural network is used to forecast the total retail sale of consumer goods of Sichuan Province, China. Empirical results indicate that the new algorithm is superior to the traditional BP network algorithm in predicting accuracy and time consumption, which shows the feasibility and effectiveness of the new algorithm.

  11. VprBP Has Intrinsic Kinase Activity Targeting Histone H2A and Represses Gene Transcription

    PubMed Central

    Kim, Kyunghwan; Kim, Jin-Man; Kim, Joong-Sun; Choi, Jongkyu; Lee, Yong Suk; Neamati, Nouri; Song, Jin Sook; Heo, Kyu; An, Woojin

    2013-01-01

    SUMMARY Histone modifications play important roles in the regulation of gene expression and chromatin organization. VprBP has been implicated in transcriptionally silent chromatin formation and cell cycle regulation, but the molecular basis underlying such effects remains unclear. Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. VprBP is localized to a large set of tumor suppressor genes and blocks their transcription, in a manner that is dependent on its kinase activity toward H2AT120. The functional significance of VprBP-mediated H2AT120p is further underscored by the fact that RNAi knockdown and small-molecule inhibition of VprBP reactivate growth regulatory genes and impede tumor growth. Our findings establish VprBP as a major kinase responsible for H2AT120p in cancer cells and suggest that VprBP inhibition could be a new strategy for the development of anticancer therapeutics. PMID:24140421

  12. Southwest Scandinavia, 40-15 kyr BP: palaeogeography and environmental change

    NASA Astrophysics Data System (ADS)

    Houmark-Nielsen, Michael; Kjær, Kurt Henrik

    2003-12-01

    Twelve palaeogeographical reconstructions illustrate environmental changes at the southwest rim of the Scandinavian Ice Sheet 40-15 kyr BP. Synchronised land, sea and glacier configurations are based on the lithostratigraphy of tills and intertill sediments. Dating is provided by optically stimulated luminescence and calibrated accelerator mass spectrometry radiocarbon.An interstadial sequence ca. 40-30 kyr BP with boreo-arctic proglacial fjords and subarctic flora and occasional glaciation in the Baltic was succeeded by a Last Glacial Maximum sequence ca. 30-20 kyr BP, with the closure of fjords and subsequent ice streams in glacial lake basins in Kattegat and the Baltic. Steadily flowing ice from Sweden bordered the Norwegian Channel Ice Stream. A deglaciation sequence ca. 20-15 kyr BP indicates the transgression of arctic waters, retreat of the Swedish ice and advance of Baltic ice streams succeeded by a return to interstadial conditions.When ameliorated ice-free conditions prevailed in maritime regions, glaciers advanced through the Baltic and when interstadial regimes dominated the Baltic, glaciers expanded off the Norwegian coast. The largest glacier extent was reached in the North Sea around 29 kyr BP, about 22 kyr BP in Denmark and ca. 18 kyr BP in the Baltic. Our model provides new data for future numerical and qualitative landform-based models. Copyright

  13. Stress Granule Components G3BP1 and G3BP2 Play a Proviral Role Early in Chikungunya Virus Replication

    PubMed Central

    Scholte, Florine E. M.; Tas, Ali; Albulescu, Irina C.; Žusinaite, Eva; Merits, Andres; Snijder, Eric J.

    2015-01-01

    ABSTRACT Stress granules (SGs) are protein-mRNA aggregates that are formed in response to environmental stresses, resulting in translational inhibition. SGs are generally believed to play an antiviral role and are manipulated by many viruses, including various alphaviruses. GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) is a key component and commonly used marker of SGs. Its homolog G3BP2 is a less extensively studied SG component. Here, we demonstrate that Chikungunya virus (CHIKV) infection induces cytoplasmic G3BP1- and G3BP2-containing granules that differ from bona fide SGs in terms of morphology, composition, and behavior. For several Old World alphaviruses it has been shown that nonstructural protein 3 (nsP3) interacts with G3BPs, presumably to inhibit SG formation, and we have confirmed this interaction in CHIKV-infected cells. Surprisingly, CHIKV also relied on G3BPs for efficient replication, as simultaneous depletion of G3BP1 and G3BP2 reduced viral RNA levels, CHIKV protein expression, and viral progeny titers. The G3BPs colocalized with CHIKV nsP2 and nsP3 in cytoplasmic foci, but no colocalization with nsP1, nsP4, or dsRNA was observed. Furthermore, G3BPs could not be detected in a cellular fraction enriched for CHIKV replication/transcription complexes, suggesting that they are not directly involved in CHIKV RNA synthesis. Depletion of G3BPs did not affect viral entry, translation of incoming genomes, or nonstructural polyprotein processing but resulted in severely reduced levels of negative-stranded (and consequently also positive-stranded) RNA. This suggests a role for the G3BPs in the switch from translation to genome amplification, although the exact mechanism by which they act remains to be explored. IMPORTANCE Chikungunya virus (CHIKV) causes a severe polyarthritis that has affected millions of people since its reemergence in 2004. The lack of approved vaccines or therapeutic options and the ongoing explosive outbreak in the

  14. Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation

    PubMed Central

    2012-01-01

    Background Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco’s modified Eagle’s medium) can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM) and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Results Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. Conclusions In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth. PMID:22889258

  15. Missing the target: Characterization of bullous pemphigoid patients who are negative using the BP180 enzyme-linked immunosorbant assay

    PubMed Central

    Fairley, Janet A.; Bream, Matthew; Fullenkamp, Colleen; Syrbu, Sergei; Chen, Mei; Messingham, Kelly N.

    2016-01-01

    Background Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoanti-bodies specific for the 180-kd BP antigen-2 (BP180) (also termed “type XVII collagen”) protein. The BP180 enzyme-linked immunosorbent assay (ELISA) is specific for the immunodominant NC16A domain of the protein. However, we and others have observed patients whose reactivity to BP180 is exclusive of the NC16A domain (referred to henceforth as non-NC16A BP). Objective We sought to determine the incidence of non-NC16A BP and identify regions of reactivity within the BP180 protein. Methods Sera from 51 patients who met the clinical and histologic criteria for BP were screened for NC16A reactivity by ELISA. Sera that were negative by ELISA were screened for IgG reactivity to an epidermal extract, recombinant BP180 protein, and subregions of BP180, by immunoblot. Demographic and clinical data were also collected on all patients. Results Four sera (7.8%) were negative using the BP180 ELISA but positive for IgG reactivity to the extracellular domain of BP180. Further mapping identified 4 regions outside of NC16A recognized by these sera: amino acid (AA) 1280 to 1315, AA 1080 to 1107, AA 1331 to 1404, and AA 1365 to 1413. One of these sera also had IgE specific for NC16A. One patient had an atypical presentation with lesions limited to the lower aspect of the legs and scarring of the nail beds. Limitations The small total number of patients with non-NC16A BP limits the identification of demographic or clinical correlates. Conclusion It is significant that 7.8% of sera from patients with new BP react to regions of BP180 exclusively outside of NC16A and, thus, would not be identified using the currently available BP180 ELISA. PMID:23083837

  16. Electronic Communications and Home Blood Pressure Monitoring (e-BP) study: Design, delivery, and evaluation framework

    PubMed Central

    Green, Beverly B.; Ralston, James D.; Fishman, Paul A.; Catz, Sheryl L.; Cook, Andrea; Carlson, Jim; Tyll, Lynda; Carrell, David; Thompson, Robert S.

    2009-01-01

    Background Randomized controlled trials have provided unequivocal evidence that treatment of hypertension decreases mortality and major disability from cardiovascular disease; however, blood pressure remains inadequately treated in most affected individuals. This large gap continues despite the facts that more than 90% of adults with hypertension have health insurance, and hypertension is the leading cause of visits to the doctor. New approaches are needed to improve hypertension care. Objectives The Electronic Communications and Home Blood Pressure Monitoring (e-BP) study is a three-arm randomized controlled trial designed to determine whether care based on the Chronic Care Model and delivered over the Internet improves hypertension care. The primary study outcomes are systolic, diastolic, and blood pressure control; secondary outcomes are medication adherence, patient self-efficacy, satisfaction and quality of life, and healthcare utilization and costs. Methods Hypertensive patients receiving care at Group Health medical centers are eligible if they have uncontrolled blood pressure on two screening visits and access to the Web and an e-mail address. Study participants are randomly assigned to three intervention groups: (a) usual care; (b) home blood pressure monitoring receipt and proficiency training on its use and the Group Health secure patient website (with secure e-mail access to their healthcare provider, access to a shared medical record, prescription refill and other services); or (c) this plus pharmacist care management (collaborative care management between the patient, the pharmacist, and the patient’s physician via a secure patient website and the electronic medical record). Conclusion We will determine whether a new model of patient-centered care that leverages Web communications, self-monitoring, and collaborative care management improves hypertension control. If this model proves successful and cost-effective, similar interventions could be used

  17. Seafood Contamination after the BP Gulf Oil Spill and Risks to Vulnerable Populations: A Critique of the FDA Risk Assessment

    PubMed Central

    Wong, Karen K.; Solomon, Gina M.

    2011-01-01

    Background: The BP oil spill of 2010 resulted in contamination of one of the most productive fisheries in the United States by polycyclic aromatic hydrocarbons (PAHs). PAHs, which can accumulate in seafood, are known carcinogens and developmental toxicants. In response to the oil spill, the U.S. Food and Drug Administration (FDA) developed risk criteria and established thresholds for allowable levels [levels of concern (LOCs)] of PAH contaminants in Gulf Coast seafood. Objectives: We evaluated the degree to which the FDA’s risk criteria adequately protect vulnerable Gulf Coast populations from cancer risk associated with PAHs in seafood. Discussion: The FDA LOCs significantly underestimate risk from seafood contaminants among sensitive Gulf Coast populations by failing to a) account for the increased vulnerability of the developing fetus and child; b) use appropriate seafood consumption rates; c) include all relevant health end points; and d) incorporate health-protective estimates of exposure duration and acceptable risk. For benzo[a]pyrene and naphthalene, revised LOCs are between two and four orders of magnitude below the level set by the FDA. Comparison of measured levels of PAHs in Gulf seafood with the revised LOCs revealed that up to 53% of Gulf shrimp samples were above LOCs for pregnant women who are high-end seafood consumers. Conclusions: FDA risk assessment methods should be updated to better reflect current risk assessment practices and to protect vulnerable populations such as pregnant women and children. PMID:21990339

  18. Biocompatible, smooth, plasma-treated nickel-titanium surface--an adequate platform for cell growth.

    PubMed

    Chrzanowski, W; Szade, J; Hart, A D; Knowles, J C; Dalby, M J

    2012-02-01

    High nickel content is believed to reduce the number of biomedical applications of nickel-titanium alloy due to the reported toxicity of nickel. The reduction in nickel release and minimized exposure of the cell to nickel can optimize the biocompatibility of the alloy and increase its use in the application where its shape memory effects and pseudoelasticity are particularly useful, e.g., spinal implants. Many treatments have been tried to improve the biocompatibility of Ni-Ti, and results suggest that a native, smooth surface could provide sufficient tolerance, biologically. We hypothesized that the native surface of nickel-titanium supports cell differentiation and insures good biocompatibility. Three types of surface modifications were investigated: thermal oxidation, alkali treatment, and plasma sputtering, and compared with smooth, ground surface. Thermal oxidation caused a drop in surface nickel content, while negligible chemistry changes were observed for plasma-modified samples when compared with control ground samples. In contrast, alkali treatment caused significant increase in surface nickel concentration and accelerated nickel release. Nickel release was also accelerated in thermally oxidized samples at 600 °C, while in other samples it remained at low level. Both thermal oxidation and alkali treatment increased the roughness of the surface, but mean roughness R(a) was significantly greater for the alkali-treated ones. Ground and plasma-modified samples had 'smooth' surfaces with R(a)=4 nm. Deformability tests showed that the adhesion of the surface layers on samples oxidized at 600 °C and alkali treatment samples was not sufficient; the layer delaminated upon deformation. It was observed that the cell cytoskeletons on the samples with a high nickel content or release were less developed, suggesting some negative effects of nickel on cell growth. These effects were observed primarily during initial cell contact with the surface. The most favorable

  19. MR Scanner Systems Should Be Adequately Characterized in Diffusion-MRI of the Breast

    PubMed Central

    Giannelli, Marco; Sghedoni, Roberto; Iacconi, Chiara; Iori, Mauro; Traino, Antonio Claudio; Guerrisi, Maria; Mascalchi, Mario; Toschi, Nicola; Diciotti, Stefano

    2014-01-01

    Breast imaging represents a relatively recent and promising field of application of quantitative diffusion-MRI techniques. In view of the importance of guaranteeing and assessing its reliability in clinical as well as research settings, the aim of this study was to specifically characterize how the main MR scanner system-related factors affect quantitative measurements in diffusion-MRI of the breast. In particular, phantom acquisitions were performed on three 1.5 T MR scanner systems by different manufacturers, all equipped with a dedicated multi-channel breast coil as well as acquisition sequences for diffusion-MRI of the breast. We assessed the accuracy, inter-scan and inter-scanner reproducibility of the mean apparent diffusion coefficient measured along the main orthogonal directions () as well as of diffusion-tensor imaging (DTI)-derived mean diffusivity (MD) measurements. Additionally, we estimated spatial non-uniformity of (NU) and MD (NUMD) maps. We showed that the signal-to-noise ratio as well as overall calibration of high strength diffusion gradients system in typical acquisition sequences for diffusion-MRI of the breast varied across MR scanner systems, introducing systematic bias in the measurements of diffusion indices. While and MD values were not appreciably different from each other, they substantially varied across MR scanner systems. The mean of the accuracies of measured and MD was in the range [−2.3%,11.9%], and the mean of the coefficients of variation for and MD measurements across MR scanner systems was 6.8%. The coefficient of variation for repeated measurements of both and MD was < 1%, while NU and NUMD values were <4%. Our results highlight that MR scanner system-related factors can substantially affect quantitative diffusion-MRI of the breast. Therefore, a specific quality control program for assessing and monitoring the performance of MR scanner systems for diffusion-MRI of the breast is

  20. Cultural and environmental barriers to adequate iron intake among northern Kenyan schoolchildren.

    PubMed

    Shell-Duncan, Bettina; McDade, Thomas

    2005-03-01

    ," including meat, blood, and beans. Consequently, in households economically able to purchase iron-rich foods, these foods are being preferentially fed to boys. Economic development may result in improved iron status for boys, but it will be unlikely to benefit girls in the absence of a dietary modification intervention. A modification of culturally acceptable "soft foods" to include iron-rich foods may provide a sustainable approach to controlling and preventing iron deficiency in this population.

  1. Geoarchaeological evidence from Peru for a 5000 years B.P. onset of El Nino

    SciTech Connect

    Sandweiss, D.H.; Richardson, J.B. III; Rollins, H.B.

    1996-09-13

    For the tropical west coast of South America, where El Nino/Southern Oscillation (ENSO) is most pronounced, archaeological and associated paleontological deposits in northern Peru revealed a major climate change at about 5000 years before the present (yr B.P.). The data implied the presence of stable, warm tropical water as far south as 10{degrees}S during the early mid-Holocene (about 8000 to 5000 yr B.P.). These data suggest that ENSO did not occur for some millennia preceding 5000 yr B.P., when global and regional climate was warmer than today. 36 refs., 1 fig., 3 tabs.

  2. Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease.

    PubMed

    Soncini, C; Berdo, I; Draetta, G

    2001-06-28

    Degradation of cellular proteins through ubiquitination is a fundamental strategy for regulating biological pathways. De-ubiquitination, i.e. the removal of ubiquitin from proteins and peptides to which ubiquitin is attached, is catalyzed by processing proteases known as de-ubiquitinating enzymes. We are studying the biology of a family of de-ubiquitinating enzymes, the mammalian ubiquitin-specific proteases (USPs), some of which appear to play a role in growth control. Given the fact that the modes of regulation of USPs and of their substrate specificity are poorly understood, we decided to attempt the identification of USP interacting proteins. Using the yeast two-hybrid system (2HS), we have isolated a cDNA clone whose product specifically interacts with USP10 but not with other USP baits tested. The isolated clone encodes a protein known to interact with the Ras-GTPase activating protein (G3BP). This interaction was further confirmed by performing a 2HS with G3BP, which led to the isolation of USP10 encoding cDNAs. We validated the interaction between the two proteins by performing in vitro binding assays and immunoprecipitations in human cells. G3BP does not appear to be a substrate of USP10; it rather inhibits the ability of USP10 to disassemble ubiquitin chains. The USP10/G3BP complex appears to co-immunoprecipitate with ubiquitinated species that could be substrates of USP10.

  3. Cognitive Attributes, Attention, and Self-Efficacy of Adequate and Inadequate Responders in a Fourth Grade Reading Intervention

    PubMed Central

    Cho, Eunsoo; Roberts, Garrett J.; Capin, Philip; Roberts, Greg; Miciak, Jeremy; Vaughn, Sharon

    2015-01-01

    We examined cognitive attributes, attention, and self-efficacy of fourth grade struggling readers who were identified as adequate responders (n = 27), inadequate responders with comprehension only deficits (n = 46), and inadequate responders with comprehension and word reading deficits (n = 52) after receiving a multicomponent reading intervention. We also included typical readers (n = 40). These four groups were compared on measures of nonverbal reasoning, working memory, verbal knowledge, listening comprehension, phonological awareness, and rapid naming as well as on teacher ratings of attention problems and self-reported self-efficacy. The two inadequate responder groups demonstrated difficulties primarily with verbal knowledge and listening comprehension compared to typical readers and adequate responders. Phonological awareness and rapid naming differentiated the two inadequate responder groups. In addition, both inadequate responder groups showed more attention problems and low self-efficacy compared to typical readers. PMID:26997755

  4. Electrographic correlates of adequate and erroneous responses evoked by conditioned signals of different functional signs during operant learning in dogs.

    PubMed

    Dumenko, V N; Kozlov, M K

    2006-01-01

    Power spectra over the frequency range 1-225 Hz in short-term (less than 1 sec) EEG reactions arising in different areas of the cerebral cortex in response to presentation of differential signals were investigated in dogs during operant feeding behavior in conditions of both adequate and erroneous responses. The energy levels of these reactions decreased several-fold as compared with responses to positive signals, mainly because of frequencies in the high-frequency range (90-225 Hz), where power was greater than not only the traditional range of 1-30 Hz, but also the gamma range of 30-80 Hz. The frequency composition of EEG reactions in adequate responses was determined by a series of discrete frequency subgroups belonging predominantly to the high-frequency band. In erroneous reactions, the discrete structure of the corresponding EEG reactions was lost.

  5. Misarticulation caused by abnormal lingual-palatal contact in patients with cleft palate with adequate velopharyngeal function.

    PubMed

    Yamashita, Y; Michi, K

    1991-10-01

    Misarticulations produced by three patients with cleft palate (2 isolated cleft palate; 1 unilateral cleft lip, alveolus, and palate) who attained adequate velopharyngeal function and normal palatal vault by early surgical repairs were examined using electropalatography (EPG) and sound spectrography (SG). Common characteristics of lingual-palatal contact in which the contact area was broader and/or was more posterior than normal were observed. These misarticulations can be divided into three types based on the direction of the breath emission: palatalized misarticulation (in which air passes along the midline of the palate), lateral misarticulation (in which air flows laterally through the occluded dental arch), and nasopharyngeal misarticulation (in which air flows out the nose). These three are considered to be similar to intractable posterior pattern of articulation in cleft palate patients previously reported. However, these types of misarticulations can be produced by cleft patients who have achieved adequate velopharyngeal function and normal palatal vault.

  6. The Leap of a Provincial SME into the Global Market Using E-commerce: The Success of Adequate Planning

    NASA Astrophysics Data System (ADS)

    Sainz de Abajo, Beatriz; García Salcines, Enrique; Burón Fernández, F. Javier; López Coronado, Miguel; de Castro Lozano, Carlos

    The leap into the global market is not easy when it involves a provincial family business. This article demonstrates how adequate planning is fundamental in a small and medium-sized enterprise (SME) with the tight budget they have available to them, in order to be able to differentiate themselves in a highly competitive market, taking into accounts the benefits and risks involved. The Information Technology (IT) tools put in place will give the necessary support and allow for the possibility of increasing and improving the infrastructure as the company requires. An adequate strategy for the future to increases sales would be e-marketing techniques as well as the current promotions which contribute to diffusing the brand.

  7. Thermodynamic study and modelling of iron-based melts for adequate prediction of modern ladle metallurgy processes

    NASA Astrophysics Data System (ADS)

    Zaitsev, A. I.; Rodionova, I. G.; Shaposhnikov, N. G.; Zemlyanko, O. A.; Karamisheva, N. A.

    2008-02-01

    The representation of iron-based melts as associated liquids have been developed basing on the detail experimental investigation and analysis of available data on their thermodynamic properties and phase equilibria. It has allowed, for the first time, to interpret adequately the reactivity of the earth metals in the iron-based melts and to predict with high precision the reactions of metal refinement and non-metallic inclusions modifying in modern ladle metallurgy.

  8. Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

    SciTech Connect

    Boeckner, L.S.; Kies, C.

    1986-03-05

    The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10/sup -6/ was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study.

  9. Characterization of highly and moderately repetitive 500 bp Eco RI fragments from Xenopus laevis DNA.

    PubMed Central

    Hummel, S; Meyerhof, W; Korge, E; Knöchel, W

    1984-01-01

    Three different types of repetitive Eco RI fragments, which comigrate within a visible band of approximately 500 bp at gel electrophoresis of Xenopus laevis DNA Eco RI digests have been cloned and sequenced. These sequences are designated as Repetitive Eco RI Monomers: REM 1, REM 2 and REM 3. The sequences contain direct repeats, inverted repeats and palindromic elements. Genomic organization of the most abundant sequence (REM 1; 0.4% of total DNA) is that of an interspersed sequence. REM 2 (0.08%) is partly organized as an interspersed element and partly found in tandem arrangement, whereas REM 3 (0.02%) represents the tandemly repeated monomeric unit of a satellite DNA. In situ hybridization has shown that REM 1 and REM 2 sequences are found on most chromosomes, REM 1 being preferentially located on specific chromosomal loci. REM 3 is located near the centromere region of only one chromosome pair (presumably number 1). Hybridization of Northern blots from RNAs of different developmental stages revealed that REM 1, REM 2 and REM 3 sequences are transcribed and that transcription is under developmental control. Images PMID:6330690

  10. Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22.

    PubMed

    de Moura, Patricia Ribeiro; Watanabe, Leandra; Bleicher, Lucas; Colau, Didier; Dumoutier, Laure; Lemaire, Muriel M; Renauld, Jean-Christophe; Polikarpov, Igor

    2009-04-01

    Interleukin-22 (IL-22) plays an important role in the regulation of immune and inflammatory responses in mammals. The IL-22 binding protein (IL-22BP), a soluble receptor that specifically binds IL-22, prevents the IL-22/interleukin-22 receptor 1 (IL-22R1)/interleukin-10 receptor 2 (IL-10R2) complex assembly and blocks IL-22 biological activity. Here we present the crystal structure of the IL-22/IL-22BP complex at 2.75 A resolution. The structure reveals IL-22BP residues critical for IL-22 binding, which were confirmed by site-directed mutagenesis and functional studies. Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein.

  11. WS-BP: An efficient wolf search based back-propagation algorithm

    NASA Astrophysics Data System (ADS)

    Nawi, Nazri Mohd; Rehman, M. Z.; Khan, Abdullah

    2015-05-01

    Wolf Search (WS) is a heuristic based optimization algorithm. Inspired by the preying and survival capabilities of the wolves, this algorithm is highly capable to search large spaces in the candidate solutions. This paper investigates the use of WS algorithm in combination with back-propagation neural network (BPNN) algorithm to overcome the local minima problem and to improve convergence in gradient descent. The performance of the proposed Wolf Search based Back-Propagation (WS-BP) algorithm is compared with Artificial Bee Colony Back-Propagation (ABC-BP), Bat Based Back-Propagation (Bat-BP), and conventional BPNN algorithms. Specifically, OR and XOR datasets are used for training the network. The simulation results show that the WS-BP algorithm effectively avoids the local minima and converge to global minima.

  12. DLC/BP ultra durable LWIR protective coatings for ZnS windows

    NASA Astrophysics Data System (ADS)

    Li, Qiantao; Liu, Shijun; Xiong, Changxin

    2007-12-01

    DLC/BP ultra durable LWIR (long wave infrared) protective coatings have been designed and prepared on ZnS (Zinc Sulphide) windows successfully. Both of BP and DLC coatings are deposited by RF-PECVD (radio frequency enhanced plasma chemical vapor deposition) process, but in different chamber. The transmittance, micro-hardness and durability of DLC/BP coatings have been investigated, which are measured by FTIR spectroscopy, micro-hardness tester and simulative harsh environmental test system. The ZnS window outer face coated with DLC/BP coatings and inner face coated with high efficient antireflection coatings is also fabricated. In the band of 8~11.5μm, the measured maximum transmittance is above 93% and the average transmittance is about 89%. The coated ZnS windows meet with the demands of LWIR electro-optics systems workable in battlefield environment.

  13. Prediction of BP reactivity to talking using hybrid soft computing approaches.

    PubMed

    Kaur, Gurmanik; Arora, Ajat Shatru; Jain, Vijender Kumar

    2014-01-01

    High blood pressure (BP) is associated with an increased risk of cardiovascular diseases. Therefore, optimal precision in measurement of BP is appropriate in clinical and research studies. In this work, anthropometric characteristics including age, height, weight, body mass index (BMI), and arm circumference (AC) were used as independent predictor variables for the prediction of BP reactivity to talking. Principal component analysis (PCA) was fused with artificial neural network (ANN), adaptive neurofuzzy inference system (ANFIS), and least square-support vector machine (LS-SVM) model to remove the multicollinearity effect among anthropometric predictor variables. The statistical tests in terms of coefficient of determination (R (2)), root mean square error (RMSE), and mean absolute percentage error (MAPE) revealed that PCA based LS-SVM (PCA-LS-SVM) model produced a more efficient prediction of BP reactivity as compared to other models. This assessment presents the importance and advantages posed by PCA fused prediction models for prediction of biological variables. PMID:25328536

  14. 1. ENVIRONMENT, FROM NORTHWEST, SHOWING B&P INTERLOCKING TOWER AND POWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. ENVIRONMENT, FROM NORTHWEST, SHOWING B&P INTERLOCKING TOWER AND POWER SUBSTATIONS - Baltimore & Potomac Interlocking Tower, Adjacent to AMTRAK railroad tracks in block bounded by Howard Street, Jones Falls Expressway, Maryland Avenue & Falls Road, Baltimore, Independent City, MD

  15. 78 FR 53137 - Flint Hills Resources Alaska, LLC, BP Pipelines (Alaska) Inc., ConocoPhillips Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ...Phillips Transportation Alaska, Inc., ExxonMobil Pipeline Company; Notice of Complaint Take notice that on... formal complaint against BP Pipelines (Alaska) Inc., ConocoPhillips Transportation Alaska, Inc.,...

  16. Environmental Conditions in northern Gulf of Mexico Estuaries: before and after the BP Oil Spill

    EPA Science Inventory

    This presentation provides a summary of ecological condition and sediment chemistry data for northern Gulf of Mexico estuaries that were exposed to oil and oil-related contaminants from the BP Oil Spill.

  17. Prediction of BP Reactivity to Talking Using Hybrid Soft Computing Approaches

    PubMed Central

    Arora, Ajat Shatru; Jain, Vijender Kumar

    2014-01-01

    High blood pressure (BP) is associated with an increased risk of cardiovascular diseases. Therefore, optimal precision in measurement of BP is appropriate in clinical and research studies. In this work, anthropometric characteristics including age, height, weight, body mass index (BMI), and arm circumference (AC) were used as independent predictor variables for the prediction of BP reactivity to talking. Principal component analysis (PCA) was fused with artificial neural network (ANN), adaptive neurofuzzy inference system (ANFIS), and least square-support vector machine (LS-SVM) model to remove the multicollinearity effect among anthropometric predictor variables. The statistical tests in terms of coefficient of determination (R 2), root mean square error (RMSE), and mean absolute percentage error (MAPE) revealed that PCA based LS-SVM (PCA-LS-SVM) model produced a more efficient prediction of BP reactivity as compared to other models. This assessment presents the importance and advantages posed by PCA fused prediction models for prediction of biological variables. PMID:25328536

  18. The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial Mediterranean fever.

    PubMed

    Yigit, Serbülent; Tural, Sengul; Tekcan, Akın; Tasliyurt, Turker; Inanir, Ahmet; Uzunkaya, Süheyla; Kismali, Gorkem

    2014-05-01

    Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.

  19. Heterostructured hBN-BP-hBN Nanodetectors at Terahertz Frequencies.

    PubMed

    Viti, Leonardo; Hu, Jin; Coquillat, Dominique; Politano, Antonio; Consejo, Christophe; Knap, Wojciech; Vitiello, Miriam S

    2016-09-01

    By reassembling thin isolated atomic planes of hexagonal borum nitride (hBN) with a few layer phosphorene black phosphorus (BP), hBN/BP/hBN heterostructures are mechanically stacked to devise high-efficiency THz photodetectors operating in the 0.3-0.65 THz range, from 4 K to 300 K, with a record signal-to-noise ratio of 20 000.

  20. Discrete Sampling Test Plan for the 200-BP-5 Operable Unit

    SciTech Connect

    Sweeney, Mark D.

    2010-02-04

    The Discrete Groundwater Sampling Project is conducted by the Pacific Northwest National Laboratory (PNNL) on behalf of CH2M HILL Plateau Remediation Company. The project is focused on delivering groundwater samples from proscribed horizons within select groundwater wells residing in the 200-BP-5 Operable Unit (200-BP-5 OU) on the Hanford Site. This document provides the scope, schedule, methodology, and other details of the PNNL discrete sampling effort.

  1. Study on the identifying of meat's visible spectrum based on BP artificial neural network

    NASA Astrophysics Data System (ADS)

    Li, Xiaotian; Zhang, Tieqiang; Li, Bo; Jiang, Yongheng; Liu, Binghui; Li, Zhaokai

    2006-01-01

    A method to identify different meat by the visible and reflected spectra of meat with BP artificial neural net (BP-ANN) was introduced in this paper. The visible and reflected spectra (from 420 to 535nm) of different meat (beef and pork) were measured with fiber sensor spectrometer. A kind of ANN with a double-hidden layer was created to identify the different meat automatically. Its right ratio reaches 92.71%.

  2. Improving enantioselectivity towards tertiary alcohols using mutants of Bacillus sp. BP-7 esterase EstBP7 holding a rare GGG(X)-oxyanion hole.

    PubMed

    Fillat, Amanda; Romea, Pedro; Urpí, Fèlix; Pastor, F I Javier; Diaz, Pilar

    2014-05-01

    Lipases and esterases are important biocatalysts for synthetic organic fine chemistry. An esterase from Bacillus sp. BP-7 (EstBP7) bears in its amino acid sequence a rare GGG(A)X oxyanion hole motif, where an uncommon threonine (T) is found at the third position. Detection of this pattern motivated evaluation of the ability of EstBP7 for conversion of tertiary alcohols. The enzyme was engineered in order to optimize its performance to provide important chiral building blocks: five variants with mutations in the oxyanion hole motif were created to investigate the influence on activity and enantioselectivity in the kinetic resolution of eight acetates of tertiary alcohols. Wild-type enzyme converted all esters of tertiary alcohols assayed with low enantioselectivity, whereas some of the mutants displayed significantly increased E-values. One of the mutants (EstBP7-AGA; Mut 5) showed an E >100 towards a complex tertiary alcohol acetate (2-(4-pyridyl)but-3-yn-2-yl acetate) at low reaction temperature (4 °C). Therefore, the catalytic toolbox was expanded for biocatalysis of optically pure tertiary alcohols valuable for the pharmaceutical industry. PMID:24407449

  3. A randomized controlled trial of an automated telephone intervention to improve blood pressure control.

    PubMed

    Harrison, Teresa N; Ho, Timothy S; Handler, Joel; Kanter, Michael H; Goldberg, Ruthie A; Reynolds, Kristi

    2013-09-01

    The objective of this study was to evaluate the effectiveness of a telephonic outreach program to improve blood pressure (BP) control among patients with hypertension. The authors identified adults 18 years and older with uncontrolled BP within the previous 12 months. Patients received either an automated telephone call advising them to have a walk-in BP check (n=31,619) or usual care (n=33,154). The primary outcome was BP control at 4 weeks. Significantly more patients who received the intervention achieved BP control compared with the usual care group (32.5% vs 23.7%; P<.0001). Patients in the intervention arm with cardiovascular disease, chronic kidney disease, or diabetes mellitus achieved better BP control. Older age, female sex, and having a household income above the median were associated with BP control. When designing quality-improvement interventions to increase BP control rates, health care organizations should consider utilizing an automated telephone outreach campaign. PMID:24034658

  4. [How I treat a diabetes type 2 patient: the DREAM project for better general practitioner-specialist collaboration. Diabetes Reinforcement of Adequate Management].

    PubMed

    Scheen, A J

    1998-02-01

    Type 2 diabetes is an important public health problem because of its high prevalence and morbidity rate which both are associated with a considerable social and human cost. The general practitioner should play a central role in the management of patients with type 2 diabetes and try to meet the therapeutic objectives. Main goals include reinforcement of early diagnosis, by a better screening of individuals at risk for type 2 diabetes, achievement of a good glycaemic control, through an optimized antidiabetic treatment, correction of associated risk factors as well as detection and treatment of disease complications. DREAM ("Diabetes Reinforcement of Adequate Management") is a pilot project which started in Liege area end 1997 for at least 2 years. It aims at improving the management of type 2 diabetic patients through a better free collaboration between general practitioners and diabetologists and the adhesion to an optimized therapeutic strategy. This ambitious project benefits from the valuable support of three pharmaceutical companies.

  5. Regulation of B cell differentiation by the ubiquitin-binding protein TAX1BP1

    PubMed Central

    Matsushita, Nobuko; Suzuki, Midori; Ikebe, Emi; Nagashima, Shun; Inatome, Ryoko; Asano, Kenichi; Tanaka, Masato; Matsushita, Masayuki; Kondo, Eisaku; Iha, Hidekatsu; Yanagi, Shigeru

    2016-01-01

    Tax1-binding protein 1 (TAX1BP1) is a ubiquitin-binding protein that restricts nuclear factor-κB (NF-κB) activation and facilitates the termination of aberrant inflammation. However, its roles in B-cell activation and differentiation are poorly understood. To evaluate the function of TAX1BP1 in B cells, we established TAX1BP1-deficient DT40 B cells that are hyper-responsive to CD40-induced extracellular signal-regulated kinase (ERK) activation signaling, exhibit prolonged and exaggerated ERK phosphorylation and show enhanced B lymphocyte-induced maturation protein 1 (Blimp-1; a transcription factor inducing plasma cell differentiation) expression that is ERK-dependent. Furthermore, TAX1BP1-deficient cells exhibit significantly decreased surface IgM expression and increased IgM secretion. Moreover, TAX1BP1-deficient mice display reduced germinal center formation and antigen-specific antibody production. These findings show that TAX1BP1 restricts ERK activation and Blimp-1 expression and regulates germinal center formation. PMID:27515252

  6. HP1BP3, a Chromatin Retention Factor for Co-transcriptional MicroRNA Processing.

    PubMed

    Liu, Haoming; Liang, Chunyang; Kollipara, Rahul K; Matsui, Masayuki; Ke, Xiong; Jeong, Byung-Cheon; Wang, Zhiqiang; Yoo, Kyoung Shin; Yadav, Gaya P; Kinch, Lisa N; Grishin, Nicholas V; Nam, Yunsun; Corey, David R; Kittler, Ralf; Liu, Qinghua

    2016-08-01

    Recent studies suggest that the microprocessor (Drosha-DGCR8) complex can be recruited to chromatin to catalyze co-transcriptional processing of primary microRNAs (pri-miRNAs) in mammalian cells. However, the molecular mechanism of co-transcriptional miRNA processing is poorly understood. Here we find that HP1BP3, a histone H1-like chromatin protein, specifically associates with the microprocessor and promotes global miRNA biogenesis in human cells. Chromatin immunoprecipitation (ChIP) studies reveal genome-wide co-localization of HP1BP3 and Drosha and HP1BP3-dependent Drosha binding to actively transcribed miRNA loci. Moreover, HP1BP3 specifically binds endogenous pri-miRNAs and facilitates the Drosha/pri-miRNA association in vivo. Knockdown of HP1BP3 compromises pri-miRNA processing by causing premature release of pri-miRNAs from the chromatin. Taken together, these studies suggest that HP1BP3 promotes co-transcriptional miRNA processing via chromatin retention of nascent pri-miRNA transcripts. This work significantly expands the functional repertoire of the H1 family of proteins and suggests the existence of chromatin retention factors for widespread co-transcriptional miRNA processing.

  7. CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.

    PubMed

    De Luca, Paola; Dalton, Guillermo N; Scalise, Georgina D; Moiola, Cristian P; Porretti, Juliana; Massillo, Cintia; Kordon, Edith; Gardner, Kevin; Zalazar, Florencia; Flumian, Carolina; Todaro, Laura; Vazquez, Elba S; Meiss, Roberto; De Siervi, Adriana

    2016-04-01

    Metabolic syndrome (MeS) has been identified as a risk factor for breast cancer. C-terminal binding protein 1 (CtBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. High fat diet (HFD) increases intracellular NADH. We investigated the effect of CtBP1 hyperactivation by HFD intake on mouse breast carcinogenesis. We generated a MeS-like disease in female mice by chronically feeding animals with HFD. MeS increased postnatal mammary gland development and generated prominent duct patterns with markedly increased CtBP1 and Cyclin D1 expression. CtBP1 induced breast cancer cells proliferation. Serum from animals with MeS enriched the stem-like/progenitor cell population from breast cancer cells. CtBP1 increased breast tumor growth in MeS mice modulating multiple genes and miRNA expression implicated in cell proliferation, progenitor cells phenotype, epithelial to mesenchymal transition, mammary development and cell communication in the xenografts. These results define a novel function for CtBP1 in breast carcinogenesis.

  8. Lysine methylation-dependent binding of 53BP1 to the pRb tumor suppressor.

    PubMed

    Carr, Simon M; Munro, Shonagh; Zalmas, Lykourgos-Panagiotis; Fedorov, Oleg; Johansson, Catrine; Krojer, Tobias; Sagum, Cari A; Bedford, Mark T; Oppermann, Udo; La Thangue, Nicholas B

    2014-08-01

    The retinoblastoma tumor suppressor protein pRb is a key regulator of cell cycle progression and mediator of the DNA damage response. Lysine methylation at K810, which occurs within a critical Cdk phosphorylation motif, holds pRb in the hypophosphorylated growth-suppressing state. We show here that methyl K810 is read by the tandem tudor domain containing tumor protein p53 binding protein 1 (53BP1). Structural elucidation of 53BP1 in complex with a methylated K810 pRb peptide emphasized the role of the 53BP1 tandem tudor domain in recognition of the methylated lysine and surrounding residues. Significantly, binding of 53BP1 to methyl K810 occurs on E2 promoter binding factor target genes and allows pRb activity to be effectively integrated with the DNA damage response. Our results widen the repertoire of cellular targets for 53BP1 and suggest a previously unidentified role for 53BP1 in regulating pRb tumor suppressor activity.

  9. CacyBP/SIP binds ERK1/2 and affects transcriptional activity of Elk-1

    SciTech Connect

    Kilanczyk, Ewa; Filipek, Slawomir; Jastrzebska, Beata; Filipek, Anna

    2009-02-27

    In this work we showed for the first time that mouse CacyBP/SIP interacts with extracellular signal regulated kinases 1 and 2 (ERK1/2). We also established that a calcium binding protein, S100A6, competes for this interaction. Moreover, the E217K mutant of CacyBP/SIP does not bind significantly to ERK1/2 although it retains the ability to interact with S100A6. Molecular modeling shows that the E217K mutation in the 189-219 CacyBP/SIP fragment markedly changes its electrostatic potential, suggesting that the binding with ERK1/2 might have an electrostatic character. We also demonstrate that CacyBP/SIP-ERK1/2 interaction inhibits phosphorylation of the Elk-1 transcription factor in vitro and in the nuclear fraction of NB2a cells. Altogether, our data suggest that the binding of CacyBP/SIP with ERK1/2 might regulate Elk-1 phosphorylation/transcriptional activity and that S100A6 might further modulate this effect via Ca{sup 2+}-dependent interaction with CacyBP/SIP and competition with ERK1/2.

  10. CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs

    PubMed Central

    De Luca, Paola; Dalton, Guillermo N.; Scalise, Georgina D.; Moiola, Cristian P.; Porretti, Juliana; Massillo, Cintia; Kordon, Edith; Gardner, Kevin; Zalazar, Florencia; Flumian, Carolina; Todaro, Laura; Vazquez, Elba S.; Meiss, Roberto; De Siervi, Adriana

    2016-01-01

    Metabolic syndrome (MeS) has been identified as a risk factor for breast cancer. C-terminal binding protein 1 (CtBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD+/NADH ratio. High fat diet (HFD) increases intracellular NADH. We investigated the effect of CtBP1 hyperactivation by HFD intake on mouse breast carcinogenesis. We generated a MeS-like disease in female mice by chronically feeding animals with HFD. MeS increased postnatal mammary gland development and generated prominent duct patterns with markedly increased CtBP1 and Cyclin D1 expression. CtBP1 induced breast cancer cells proliferation. Serum from animals with MeS enriched the stem-like/progenitor cell population from breast cancer cells. CtBP1 increased breast tumor growth in MeS mice modulating multiple genes and miRNA expression implicated in cell proliferation, progenitor cells phenotype, epithelial to mesenchymal transition, mammary development and cell communication in the xenografts. These results define a novel function for CtBP1 in breast carcinogenesis. PMID:26933806

  11. The preparation of BP single crystals by high pressure flux method

    NASA Technical Reports Server (NTRS)

    Kumashiro, Y.; Misawa, S.; Gonda, S.

    1984-01-01

    Single crystals of BP, a III-V compound semiconductor, were obtained by the high pressure flux method. Cu3P and Ni12P5 powders were used as the flux, and mixed with BP powder. Two kinds of mixtures were prepared: (1) 1.8g (BP) + 35 G (Cu3P) and (2) 1.7 g (BP) + 25 g (Ni12P5). They were compressed into pellets, heated at 1300 C for 24 h in an induction furnace under a pressure of 1 MPa using Ar-P2 gas, and slowly cooled to room temperature. In case (1), BP single crystals grew along the (III) plane, and in case (2) they grew as an aggregate of crystallites. The cathodoluminescence spectra of the synthetic BP crystals showed peaks near 680 nm (1.82 eV) for case (1), and 500 nm (2.47 eV) for case (2). By using the high pressure flux method conventional sized crystals were obtained in a relatively short time.

  12. 15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: a series of 52 patients.

    PubMed

    Vanlerberghe, Clémence; Petit, Florence; Malan, Valérie; Vincent-Delorme, Catherine; Bouquillon, Sonia; Boute, Odile; Holder-Espinasse, Muriel; Delobel, Bruno; Duban, Bénédicte; Vallee, Louis; Cuisset, Jean-Marie; Lemaitre, Marie-Pierre; Vantyghem, Marie-Christine; Pigeyre, Marie; Lanco-Dosen, Sandrine; Plessis, Ghislaine; Gerard, Marion; Decamp, Matthieu; Mathieu, Michèle; Morin, Gilles; Jedraszak, Guillaume; Bilan, Frédéric; Gilbert-Dussardier, Brigitte; Fauvert, Delphine; Roume, Joëlle; Cormier-Daire, Valérie; Caumes, Roseline; Puechberty, Jacques; Genevieve, David; Sarda, Pierre; Pinson, Lucie; Blanchet, Patricia; Lemeur, Nathalie; Sheth, Frenny; Manouvrier-Hanu, Sylvie; Andrieux, Joris

    2015-03-01

    Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies.

  13. Occurrence of 4-tert-butylphenol (4-t-BP) biodegradation in an aquatic sample caused by the presence of Spirodela polyrrhiza and isolation of a 4-t-BP-utilizing bacterium.

    PubMed

    Ogata, Yuka; Toyama, Tadashi; Yu, Ning; Wang, Xuan; Sei, Kazunari; Ike, Michihiko

    2013-04-01

    Although 4-tert-butylphenol (4-t-BP) is a serious aquatic pollutant, its biodegradation in aquatic environments has not been well documented. In this study, 4-t-BP was obviously and repeatedly removed from water from four different environments in the presence of Spirodela polyrrhiza, giant duckweed, but 4-t-BP persisted in the environmental waters in the absence of S. polyrrhiza. Also, 4-t-BP was not removed from autoclaved pond water with sterilized S. polyrrhiza. These results suggest that the 4-t-BP removal from the environmental waters was caused by biodegradation stimulated by the presence of S. polyrrhiza rather than by uptake by the plant. Moreover, Sphingobium fuliginis OMI capable of utilizing 4-t-BP as a sole carbon and energy source was isolated from the S. polyrrhiza rhizosphere. Strain OMI degraded 4-t-BP via a meta-cleavage pathway, and also degraded a broad range of alkylphenols with linear or branched alkyl side chains containing two to nine carbon atoms. Root exudates of S. polyrrhiza stimulated 4-t-BP degradation and cell growth of strain OMI. Thus, the stimulating effects of S. polyrrhiza root exudates on 4-t-BP-degrading bacteria might have contributed to 4-t-BP removal in the environmental waters with S. polyrrhiza. These results demonstrate that the S. polyrrhiza-bacteria association may be applicable to the removal of highly persistent 4-t-BP from wastewaters or polluted aquatic environments.

  14. Severe neonatal marfan syndrome resulting from a De Novo 3-bp insertion into the fibrillin gene on chromosome 15

    SciTech Connect

    Milewicz, D.M.; Duvic, M. )

    1994-03-01

    Severe neonatal Marfan syndrome has features of the Marfan syndrome and congenital contractural arachnodactyly present at birth, along with unique features such as loose, redundant skin and pulmonary emphysema. Since the Marfan syndrome and congenital contractural arachnodactyly are due to mutations in different genes, it has been uncertain whether neonatal Marfan syndrome is due to mutations in the fibrillin gene on chromosome 15 or in another gene. The authors studied an infant with severe neonatal Marfan syndrome. Dermal fibroblasts were metabolically labeled and found to secrete fibrillin inefficiently when compared with control cells. Reverse transcription and amplification of the proband's fibroblast RNA was used to identify a 3-bp insertion between nucleotides 480-481 or 481-482 of the fibrillin cDNA. The insertion maintains the reading frame of the protein and inserts a cysteine between amino acids 160 and 161 in an epidermal growth-factor-like motif of fibrillin. This 3-bp insertion was not found in the fibrillin gene in 70 unrelated, unaffected individuals and 11 unrelated individuals with the Maran syndrome. The authors conclude that neonatal Marfan syndrome is the result of mutations in the fibrillin gene on chromosome 15 and is part of the Marfan syndrome spectrum. 32 refs., 3 figs.

  15. Solution structure of the THAP domain from Caenorhabditis elegans C-terminal binding protein (CtBP).

    PubMed

    Liew, Chu Kong; Crossley, Merlin; Mackay, Joel P; Nicholas, Hannah R

    2007-02-16

    The THAP (Thanatos-associated protein) domain is a recently discovered zinc-binding domain found in proteins involved in transcriptional regulation, cell-cycle control, apoptosis and chromatin modification. It contains a single zinc atom ligated by cysteine and histidine residues within a Cys-X(2-4)-Cys-X(35-53)-Cys-X(2)-His consensus. We have determined the NMR solution structure of the THAP domain from Caenorhabditis elegans C-terminal binding protein (CtBP) and show that it adopts a fold containing a treble clef motif, bearing similarity to the zinc finger-associated domain (ZAD) from Drosophila Grauzone. The CtBP THAP domain contains a large, positively charged surface patch and we demonstrate that this domain can bind to double-stranded DNA in an electrophoretic mobility-shift assay. These data, together with existing reports, indicate that THAP domains might exhibit a functional diversity similar to that observed for classical and GATA-type zinc fingers. PMID:17174978

  16. Uncoupling protein 2 gene (UCP2) 45-bp I/D polymorphism is associated with adiposity among Malaysian women.

    PubMed

    Say, Yee-How; Ban, Zi-Lian; Arumugam, Yogambigai; Kaur, Trishal; Tan, Mee-Lay; Chia, Phee-Phee; Fan, Sook-Ha

    2014-12-01

    This study investigated the association of Uncoupling Protein 2 gene (UCP2) 45-bp I/D polymorphism with obesity and adiposity in 926 Malaysian subjects (416 males;265 obese; 102/672/152 Malays/Chinese/Indians). The overall minor allele frequency (MAF) was 0.14, while MAFs according to Malay/Chinese/Indian were 0.17/0.12/0.21. The polymorphism was associated with ethnicity, obesity and overall adiposity (total body fat percentage, TBF), but not gender and central adiposity (waist-hip ratio, WHR). Gender- and ethnicity-stratified analysis revealed that within males, the polymorphism was not associated with ethnicity and anthropometric classes. However, within females, significantly more Indians, obese and those with high TBF carried I allele. Logistic regression analysis among females further showed the polymorphism was associated with obesity and overall adiposity; however, when adjusted for age and ethnicity, this association was abolished for obesity but remained significant for overall adiposity [Odds Ratio (OR) for ID genotype = 2.02 (CI=1.18, 3.45; p=0.01); I allele =1.81 (CI=1.15, 2.84; p=0.01)]. Indeed, covariate analysis controlling for age and ethnicity also showed that those carrying ID genotype or I allele had significantly higher TBF than the rest. In conclusion, UCP2 45-bp I/D polymorphism is associated with overall adiposity among Malaysian women. PMID:25431415

  17. Identification and characterization of a novel calcyclin binding protein (CacyBP) gene from Apis cerana cerana.

    PubMed

    Yu, Xiaoli; Lu, Wenjing; Sun, Rujiang; Guo, Xingqi; Xu, Baohua

    2012-08-01

    Calcyclin binding protein (CacyBP), a homolog of Sgt1, was shown to interact with some S100 proteins, Skp1, tubulin, actin and ERK1/2 kinases. Studies have also shown that CacyBP is a neuronal protein in mammals. Limited information is available regarding the properties and functions of CacyBP in insects. Here, we cloned and characterized a novel CacyBP gene, named AccCacyBP, from honeybee (Apis cerana cerana). Bioinformatic analysis indicated that AccCacyBP was highly conserved and closely related to the CacyBP of other insects. Promoter analysis revealed a number of putative tissue, development and stress-related transcription factor-binding sites. RT-qPCR demonstrated that AccCacyBP was expressed at all of the stages of development, especially in the brains of honeybees. Moreover, immunohistochemistry analysis showed the presence of AccCacyBP in the brain. The transcript levels of AccCacyBP in the brains of honeybees were developmentally induced and upregulated by exposure to oxidative stresses, including UV-light, acetamiprid and HgCl(2). This study demonstrates that the CacyBP gene in honeybees may be a neuronal protein involved in the developmental regulation and the stress-response of the brain of honeybees. PMID:22539186

  18. Association of HLA-G promoter and 14-bp insertion-deletion variants with acute allograft rejection and end-stage renal disease.

    PubMed

    Misra, M K; Prakash, S; Kapoor, R; Pandey, S K; Sharma, R K; Agrawal, S

    2013-11-01

    The aim of this study was to investigate the HLA-G 14-bp insertion/deletion (I/D) polymorphism among end-stage renal disease (ESRD) patients. Cytomegalovirus (CMV) infection, acute allograft rejection (AR) and overall survival after renal transplantation was investigated in 300 ESRD patients and 302 age, sex and ethnicity-matched controls. Sequencing was performed to evaluate the impact of HLA-G promoter region single-nucleotide polymorphisms (SNPs) whereas semi-quantitative PCR method was used to determine the probable HLA-G expression pattern among ESRD and AR cases. Further, soluble human leukocyte antigen (HLA)-G (sHLA-G) expression levels were compared in AR vs non-AR cases in the light of HLA-G 14-bp I/D polymorphism. Increased risk was found for 14-bp D/D (deletion-DD) genotype and 14-bp D allele [DD: odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.03-2.06, P value = 0.0358; D: OR = 1.29, 95% CI = 1.03-1.62, P value = 0.0277], respectively for ESRD and CMV infection (DD: OR = 2.70, 95% CI = 1.45-5.05, P value = 0.0021; D: OR = 1.94, 95% CI = 1.22-3.08, P value = 0.0052). Nearly fourfold (OR = 3.62, 95%CI = 1.61-8.14, p = 0.0039) risk was observed for 14-bp I/I (insertion-II) genotype for AR. Survival analysis showed increased overall survival (OS) (AR or death) for 14-bp D/D genotype. HLA-G promoter region sequencing was carried out among 60 ESRD patients and 100 normal controls which showed increased risk for -964 G>A, -725 C>G/T and -486 A>C SNPs. -964 G>A and -725 C>G/T SNPs showed risk association for AR patients. High level of HLA-G transcripts was observed among non-AR patients. Further soluble HLA-G (sHLA-G) showed increased levels in ESRD patients (mean ± SEM; 62.16 ± 2.43 U/ml) as compared to controls (mean ± SEM; 21.06 ± 3.89 U/ml) (P = <0.0001). The 14-bp I/I, 14-bp I/D and 14-bp D/D genotypes showed significantly higher levels of sHLA-G among non-AR as

  19. Challenges and coping strategies of orphaned children in Tanzania who are not adequately cared for by adults.

    PubMed

    Daniel, Marguerite; Mathias, Angela

    2012-10-01

    Orphaned children in poor rural communities sometimes have no adult who is able to care for them or else the adult caregiver is not able to provide adequate care. Tanzania remains one of the poorest countries in the world, and poverty frequently constrains foster care. Although HIV prevalence is declining, AIDS is still a major cause of orphaning. This article explores the challenges and coping strategies accompanying two possible life trajectories for orphaned children without adequate adult care: 1) that they remain in rural areas in child-headed households, or 2) that they are trafficked to an urban area. Antonovsky's salutogenic model is used as the theoretical framework. The data come from two separate phenomenological studies with vulnerable children. In the first study, in-depth interviews were held with 12 orphaned children in a poor rural area; data concerning three child heads of households are included here. In the second study, 15 girls who were trafficked from rural areas to Dar es Salaam gave extended life-history narrations; data are included for nine of the girls who were orphaned. Loss of parents, a lack of cash, and the need to balance school attendance with food production were chronic stressors for the children heading households, while resources included income-generation strategies and the ability to negotiate with teachers for time to cultivate. For the trafficked girls chronic stressors included exploitation, long working hours, little or no pay, isolation and rape. Resources for them, although limited, included faith networks and neighbours; escape from the exploitative situation frequently involved external help. We conclude that given physical and social assets the child-headed households were able to cope with the challenges of caring for themselves and a younger child, but isolation and dependency on employers made it difficult for the trafficked girls to cope with this exploitation. The salutogenic model proved a useful tool in

  20. Receptor-level interrelationships of amino acids and the adequate amino acid type hormones in Tetrahymena: a receptor evolution model.

    PubMed

    Csaba, G; Darvas, Z

    1986-01-01

    Histidine stimulates the phagocytosis of Tetrahymena to the same extent as histamine, and also stimulates its division, which histamine does not. Tyrosine and diiodotyrosine equally stimulate the growth of the Tetrahymena. Both amino acids inhibit the characteristic influence of the adequate amino acid hormone when added to Tetrahymena culture 72 h in advance of it. Primary interaction with diiodotyrosine and tyrosine notably increases the cellular growth rate. Histamine has a similar, although less notable effect than histidine. In the light of these experimental observations there is reason to postulate that the receptors of the amino acid hormones have developed from amino acid receptors.