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Sample records for adequate bp control

  1. 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- ...

  2. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... production performance, or biased observation. One or more adequate and well-controlled studies are required... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Adequate and well-controlled studies. 514.117... Applications § 514.117 Adequate and well-controlled studies. (a) Purpose. The primary purpose of...

  3. 21 CFR 514.117 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... production performance, or biased observation. One or more adequate and well-controlled studies are required... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Adequate and well-controlled studies. 514.117... Applications § 514.117 Adequate and well-controlled studies. (a) Purpose. The primary purpose of...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... production performance, or biased observation. One or more adequate and well-controlled studies are required... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Adequate and well-controlled studies. 514.117... Applications § 514.117 Adequate and well-controlled studies. (a) Purpose. The primary purpose of...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... production performance, or biased observation. One or more adequate and well-controlled studies are required... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adequate and well-controlled studies. 514.117... Applications § 514.117 Adequate and well-controlled studies. (a) Purpose. The primary purpose of...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... production performance, or biased observation. One or more adequate and well-controlled studies are required... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Adequate and well-controlled studies. 514.117... Applications § 514.117 Adequate and well-controlled studies. (a) Purpose. The primary purpose of...

  7. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-evident (general anesthetics, drug metabolism). (3) The method of selection of subjects provides adequate... respect to pertinent variables such as age, sex, severity of disease, duration of disease, and use of... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Adequate and well-controlled studies....

  8. Efficacy and Tolerability of Telmisartan Plus Amlodipine in Asian Patients Not Adequately Controlled on Either Monotherapy or on Low-Dose Combination Therapy

    PubMed Central

    Zhu, Dingliang; Gao, Pingjin; Yagi, Nobutaka

    2014-01-01

    Objective. To evaluate the efficacy and safety of the telmisartan plus amlodipine (T/A) single-pill combination (SPC) in Asian patients with hypertension whose blood pressure (BP) was not adequately controlled on either monotherapy or on low-dose combination therapy. Patients and Methods. Data are presented from five Boehringer Ingelheim-sponsored phase 3, double-blind, 8-week, studies: two studies in nonresponders to amlodipine (data pooled for amlodipine), two studies on nonresponders to telmisartan (pooled data), and one on nonresponders to low-dose T/A SPC. Results. After 8 weeks' treatment, mean reductions from the reference baseline in diastolic BP (DBP; primary endpoint), systolic BP (SBP), and SBP, DBP goal, and response rates were higher with the T/A SPC than respective monotherapies. The T80/A5 SPC resulted in greater reductions in DBP and SBP, and higher DBP goal and response rate than the low-dose T40/A5 SPC. Peripheral edema incidence was low (amlodipine 0.5%, telmisartan 0.0%, and T/A SPC 0.7%). Discussion and Conclusion. In Asian patients whose BP is not adequately controlled with telmisartan or amlodipine monotherapy, T/A SPC treatment results in greater BP reduction, and higher DBP and SBP goal and response rates. The safety and tolerability of the T/A SPC are comparable to those of the respective monotherapies and consistent with those reported in previous studies. PMID:24719757

  9. 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 ...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences... recognized by the scientific community as the essentials of an adequate and well-controlled clinical... randomization and blinding of patients or investigators, or both. If the intent of the trial is to...

  11. 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...

  12. 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...

  13. 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...

  14. 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

    ... 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...

  15. 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

    ... 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...

  16. Esmolol in a case of severe tetanus. Adequate haemodynamic control achieved despite markedly elevated catecholamine levels.

    PubMed

    Beards, S C; Lipman, J; Bothma, P A; Joynt, G M

    1994-03-01

    A patient with severe tetanus, who had a sympathetic crisis while sedated with 30 mg/h diazepam and 30 mg/h morphine, is described. Satisfactory control of the haemodynamic crisis was achieved with bolus doses of esmolol to a total of 180 mg. A disturbing finding was that although there was adequate control of the tachycardia and hypertension, arterial catecholamine levels remained markedly elevated. Adrenaline levels of 531 pg/ml (normal 10-110 pg/ml) and noradrenaline levels of 1,036 pg/ml (normal 100-500 pg/ml) were recorded when the patient had a systolic arterial pressure of 110 mmHg and a heart rate of 97/min. The implications of this finding are discussed. PMID:11218441

  17. 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.

  18. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., such as spontaneous change in the course of the disease, placebo effect, or biased observation. The... control are recognized: (i) Placebo concurrent control. The test drug is compared with an inactive preparation designed to resemble the test drug as far as possible. A placebo-controlled study may...

  19. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., such as spontaneous change in the course of the disease, placebo effect, or biased observation. The... control are recognized: (i) Placebo concurrent control. The test drug is compared with an inactive preparation designed to resemble the test drug as far as possible. A placebo-controlled study may...

  20. 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

  1. Glycemic penalty index for adequately assessing and comparing different blood glucose control algorithms

    PubMed Central

    Van Herpe, Tom; De Brabanter, Jos; Beullens, Martine; De Moor, Bart; Van den Berghe, Greet

    2008-01-01

    Introduction Blood glucose (BG) control performed by intensive care unit (ICU) nurses is becoming standard practice for critically ill patients. New (semi-automated) 'BG control' algorithms (or 'insulin titration' algorithms) are under development, but these require stringent validation before they can replace the currently used algorithms. Existing methods for objectively comparing different insulin titration algorithms show weaknesses. In the current study, a new approach for appropriately assessing the adequacy of different algorithms is proposed. Methods Two ICU patient populations (with different baseline characteristics) were studied, both treated with a similar 'nurse-driven' insulin titration algorithm targeting BG levels of 80 to 110 mg/dl. A new method for objectively evaluating BG deviations from normoglycemia was founded on a smooth penalty function. Next, the performance of this new evaluation tool was compared with the current standard assessment methods, on an individual as well as a population basis. Finally, the impact of four selected parameters (the average BG sampling frequency, the duration of algorithm application, the severity of disease, and the type of illness) on the performance of an insulin titration algorithm was determined by multiple regression analysis. Results The glycemic penalty index (GPI) was proposed as a tool for assessing the overall glycemic control behavior in ICU patients. The GPI of a patient is the average of all penalties that are individually assigned to each measured BG value based on the optimized smooth penalty function. The computation of this index returns a number between 0 (no penalty) and 100 (the highest penalty). For some patients, the assessment of the BG control behavior using the traditional standard evaluation methods was different from the evaluation with GPI. Two parameters were found to have a significant impact on GPI: the BG sampling frequency and the duration of algorithm application. A higher BG

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

    PubMed

    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

  3. 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

  4. Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide.

    PubMed

    Kulke, Matthew H; O'Dorisio, Thomas; Phan, Alexandria; Bergsland, Emily; Law, Linda; Banks, Phillip; Freiman, Joel; Frazier, Kenny; Jackson, Jessica; Yao, James C; Kvols, Larry; Lapuerta, Pablo; Zambrowicz, Brian; Fleming, Douglas; Sands, Arthur

    2014-10-01

    Serotonin produced by neuroendocrine tumors is believed to be a principal cause of the diarrhea in carcinoid syndrome. We assessed the safety and efficacy of telotristat etiprate, an oral serotonin synthesis inhibitor, in patients with diarrhea associated with carcinoid syndrome. In this prospective, randomized study, patients with evidence of carcinoid tumor and ≥4 bowel movements (BMs)/day despite stable-dose octreotide LAR depot therapy were enrolled in sequential, escalating, cohorts of four patients per cohort. In each cohort, one patient was randomly assigned to placebo and three patients to telotristat etiprate, at 150, 250, 350, or 500 mg three times a day (tid). In a subsequent cohort, one patient was assigned to placebo and six patients to telotristat etiprate 500 mg tid. Patients were assessed for safety, BM frequency (daily diary), 24 h urinary 5-hydroxyindoleacetic acid (u5-HIAA), and adequate relief of carcinoid gastrointestinal symptoms (using a weekly questionnaire). Twenty-three patients were treated: 18 received telotristat etiprate and five received placebo. Adverse events were generally mild. Among evaluable telotristat etiprate-treated patients, 5/18 (28%) experienced a ≥30% reduction in BM frequency for ≥2 weeks, 9/16 (56%) experienced biochemical response (≥50% reduction or normalization in 24-h u5-HIAA) at week 2 or 4, and 10/18 (56%) reported adequate relief during at least 1 of the first 4 weeks of treatment. Similar activity was not observed in placebo-treated patients. Telotristat etiprate was well tolerated. Our observations suggest that telotristat etiprate has activity in controlling diarrhea associated with carcinoid syndrome. Further studies confirming these findings are warranted. PMID:25012985

  5. Telotristat Etiprate, a Novel Serotonin Synthesis Inhibitor, in Patients with Carcinoid Syndrome and Diarrhea Not Adequately Controlled by Octreotide

    PubMed Central

    Kulke, Matthew H.; O’Dorisio, Thomas; Phan, Alexandria; Bergsland, Emily; Law, Linda; Banks, Phillip; Freiman, Joel; Frazier, Kenny; Jackson, Jessica; Yao, James C.; Kvols, Larry; Lapuerta, Pablo; Zambrowicz, Brian; Fleming, Douglas; Sands, Arthur

    2014-01-01

    Serotonin produced by neuroendocrine tumors is believed to be a principal cause of the diarrhea in carcinoid syndrome. We assessed the safety and efficacy of telotristat etiprate, an oral serotonin synthesis inhibitor, in patients with diarrhea associated with carcinoid syndrome. In this prospective, randomized study, patients with evidence of carcinoid tumor and ≥4 bowel movements (BMs)/day despite stable-dose octreotide LAR depot therapy were enrolled in sequential, escalating, cohorts of 4 patients/cohort. In each cohort, 1 patient was randomly assigned to placebo and 3 patients to telotristat etiprate, at 150, 250, 350, or 500 mg 3x/day (tid). In a subsequent cohort, 1 patient was assigned to placebo and 6 patients to telotristat etiprate 500 mg tid. Patients were assessed for safety, BM frequency (daily diary), 24-hour urinary 5-hydroxyindoleacetic acid (u5-HIAA), and adequate relief of carcinoid gastrointestinal symptoms (using a weekly questionnaire). Twenty-three patients were treated; 18 received telotristat etiprate and 5 received placebo. Adverse events were generally mild. Among evaluable telotristat etiprate-treated patients, 5/18 (28%) experienced a ≥30% reduction in BM frequency for ≥2 weeks, 9/16 (56%) experienced biochemical response (≥50% reduction or normalization in 24-hour u5-HIAA) at Week 2 or 4, and 10/18 (56%) reported adequate relief during at least 1 of the first 4 weeks of treatment. Similar activity was not observed in placebo-treated patients. Telotristat etiprate was well tolerated. Our observations suggest that telotristat etiprate has activity in controlling diarrhea associated with carcinoid syndrome. Further studies confirming these findings are warranted. PMID:25012985

  6. Combination and triple therapy in patients with stable angina pectoris not adequately controlled by optimal β-blocker therapy

    PubMed Central

    Kok, W.E.M.; Visser, F.C.; Visser, C.A.

    2002-01-01

    In 60 to 80% of patients with stable angina pectoris at low risk for future coronary events, monotherapy with a β-blocker is an effective treatment. When patients with stable angina pectoris and low risk for events do not respond adequately to optimal β-blocker monotherapy, combination therapy or even triple therapy is may be recommended, but little is known of the actual benefit of such a strategy. We reviewed the evidence from the literature on the effectiveness of combination and triple therapy. Combination therapy with a calcium antagonist or nitrate was found to be more effective than β-blocker monotherapy in the majority of studies, but only an estimated 30% of patients objectively benefit from these combination therapies. Direct comparison shows that combination therapy of a β-blocker with a calcium antagonist is more effective than the combination of a β-blocker with a nitrate. An inadequate response to β-blocker monotherapy is more effectively improved by addition of a calcium antagonist than by alternative use of a calcium antagonist. The use of triple therapy is controversial and not recommended in patients with mild angina pectoris, while for patients with severe angina pectoris not responding to combination therapy of a β-blocker with a nitrate, triple therapy may be of advantage, although the number of patients studied has been small. PMID:25696045

  7. T4-like phage Bp7, a potential antimicrobial agent for controlling drug-resistant Escherichia coli in chickens.

    PubMed

    Zhang, Can; Li, Wenli; Liu, Wenhua; Zou, Ling; Yan, Chen; Lu, Kai; Ren, Huiying

    2013-09-01

    Chicken-pathogenic Escherichia coli is severely endangering the poultry industry in China and worldwide, and antibiotic therapy is facing an increasing problem of antibiotic resistance. Bacteriophages can kill bacteria with no known activity in human or animal cells, making them an attractive alternative to antibiotics. In this study, we present the characteristics of a novel virulent bacteriophage, Bp7, specifically infecting pathogenic multidrug-resistant E. coli. Phage Bp7 was isolated from chicken feces. Bp7 belongs to the family Myoviridae, possessing an elongated icosahedral head and contractile sheathed tail. It has a 168-kb double-stranded DNA genome. For larger yields, its optimal multiplicity of infection (MOI) to infect E. coli was about 0.001. The latent period was 10 to 15 min, and the burst size was 90 PFU/infected cell. It was stable both at pH 5.0 to 10.0 and at 40°C or 50°C for at least 1 h. Bp7 could infect 46% of pathogenic clinical E. coli strains. Bp7 harbored 791 open reading frames (ORFs) and 263 possible genes. Among the 263 genes, 199 possessed amino acid sequence identities with ORFs of phage T4, 62 had identities with other T4-like phages, and only one lacked any database match. The genome of Bp7 manifested obvious division and rearrangement compared to phages T4, JS98, and IME08. Bp7 is a new member of the "T4-like" genus, family Myoviridae. Its wide host range, strong cell-killing activity, and high stability to pH make it an alternative to antimicrobials for controlling drug-resistant E. coli in chickens. PMID:23835183

  8. Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

    SciTech Connect

    Fietkau, Rainer . E-mail: rainer.fietkau@med.uni-rostock.de; Roedel, Claus; Hohenberger, Werner; Raab, Rudolf; Hess, Clemens; Liersch, Torsten; Becker, Heinz; Wittekind, Christian; Hutter, Matthias; Hager, Eva; Karstens, Johann; Ewald, Hermann; Christen, Norbert; Jagoditsch, Michael; Martus, Peter; Sauer, Rolf

    2007-03-15

    Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

  9. NFIL3/E4BP4 controls type 2 T helper cell cytokine expression.

    PubMed

    Kashiwada, Masaki; Cassel, Suzanne L; Colgan, John D; Rothman, Paul B

    2011-05-18

    Type 2 T helper (T(H)2) cells are critical for the development of allergic immune responses; however, the molecular mechanism controlling their effector function is still largely unclear. Here, we report that the transcription factor NFIL3/E4BP4 regulates cytokine production and effector function by T(H)2 cells. NFIL3 is highly expressed in T(H)2 cells but much less in T(H)1 cells. Production of interleukin (IL)-13 and IL-5 is significantly increased in Nfil3(-/-) T(H)2 cells and is decreased by expression of NFIL3 in wild-type T(H)2 cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL-4 production is decreased in Nfil3(-/-) T(H)2 cells. Increased IL-13 and IL-5 together with decreased IL-4 production by antigen-stimulated splenocytes from the immunized Nfil3(-/-) mice was also observed. The ability of NFIL3 to alter T(H)2 cytokine production is a T-cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of T(H)2 responses. PMID:21499227

  10. Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion.

    PubMed

    Sparks, Matthew A; Stegbauer, Johannes; Chen, Daian; Gomez, Jose A; Griffiths, Robert C; Azad, Hooman A; Herrera, Marcela; Gurley, Susan B; Coffman, Thomas M

    2015-12-01

    Inappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)-dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II-dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%-10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II-dependent vascular responses in the kidney to effect natriuresis and BP control. PMID:25855778

  11. Enhancement of Bacillus subtilis Lipopeptide Biosurfactants Production through Optimization of Medium Composition and Adequate Control of Aeration

    PubMed Central

    Ghribi, Dhouha; Ellouze-Chaabouni, Semia

    2011-01-01

    Interest in biosurfactants has increased considerably in recent years, as they are potentially used in many commercial applications in petroleum, pharmaceuticals, biomedical, and food processing industries. Since improvement of their production was of great importance to reduce the final coast, cultural conditions were analyzed to optimize biosurfactants production from Bacillus subtilis SPB1 strain. A high yield of biosurfactants was obtained from a culture of B. subtilis using carbohydrate substrate as a carbon source; among carbohydrates, glucose enhanced the best surfactin production. The optimum glucose concentration was 40 g/L. Higher amount of biosurfactants was obtained using 5 g/L of urea as organic nitrogen source and applying C/N ratio of 7 with ammonium chloride as inorganic nitrogen source. The highest amount of biosurfactants was recorded with the addition of 2% kerosene. Moreover, it was shown, using an automated full-controlled 2.6 L fermenter, that aeration of the medium, which affected strongly the growth regulated biosurfactants synthesis by the producing cell. So that, low or high aerations lead to a decrease of biosurfactants synthesis yields. It was found that when using dissolved oxygen saturation of the medium at 30%, biosurfactants production reached 4.92 g/L. PMID:21966596

  12. 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 to support the reasonable belief that a particular...

  13. 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

  14. A 750 bp sensory integration region directs global control of the Escherichia coli GadE acid resistance regulator.

    PubMed

    Sayed, Atef K; Foster, John W

    2009-03-01

    Escherichia coli survives pH 2 environments through an acid resistance (AR) system regulated by the transcriptional activator GadE. Numerous proteins control gadE at an upstream, conserved, 798 bp intergenic region. We show this region produces three transcripts starting at -124 (T1), -324/-317 (T2) and -566 (T3) bp from the gadE start codon. Transcriptional lacZ fusions to gadE promoter regions revealed P1 and P3 were active while P2 alone was not. However, pairing P3 with P2 activated P2 and increased expression 20-fold above P3 alone. The fusions were transferred to Salmonella, which lacks this AR system, and plasmid-borne E. coli-specific regulators EvgA, YdeO, GadE and GadX were introduced. Data revealed that YdeO and GadX activate P3, P2 and P3P2, while GadE autoactivates P1 and represses P3 and P3P2. The developing model indicates that different signals activate YdeO, GadX, or an MnmE-dependent regulator, which stimulate gadE transcription from the P3 and P2 promoters. Once made, GadE activates P1 and represses P3 and P2. The P1 region also enables efficient downstream transcription and translation of the P3 or P2 transcripts. Evidence indicates the entire 750 bp sensory integration locus is necessary for a versatile response. PMID:19220752

  15. 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

  16. 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

  17. Negative control of circadian clock regulator E4BP4 by casein kinase Iepsilon-mediated phosphorylation.

    PubMed

    Doi, Masao; Okano, Toshiyuki; Yujnovsky, Irene; Sassone-Corsi, Paolo; Fukada, Yoshitaka

    2004-06-01

    Light-dependent transcriptional regulation of clock genes is a crucial step in the entrainment of the circadian clock. E4bp4 is a light-inducible gene in the chick pineal gland, and it encodes a bZIP protein that represses transcription of cPer2, a chick pineal clock gene. Here, we demonstrate that prolonged light period-dependent accumulation of E4BP4 protein is temporally coordinated with a delay of the rising phase of cPer2 in the morning. E4BP4 was phosphorylated progressively and then disappeared in parallel with induced cPer2 expression. Characterization of E4BP4 revealed Ser182, a phosphoacceptor site located at the amino-terminal border of the Ser/Thr cluster, which forms the phosphorylation motifs for casein kinase 1epsilon (CK1epsilon). CK1epsilon physically associated with E4BP4 and phosphorylated it. CK1epsilon-catalyzed phosphorylation of E4BP4 resulted in proteasomal proteolysis-dependent decrease of E4BP4 levels, while E4BP4 nuclear accumulation was attenuated by CK1epsilon in a kinase activity-independent manner. CK1epsilon-mediated posttranslational regulation was accompanied by reduction of the transcriptional repression executed by E4BP4. These results not only demonstrate a phosphorylation-dependent regulatory mechanism for E4BP4 function but also highlight the role of CK1epsilon as a negative regulator for E4BP4-mediated repression of cPer2. PMID:15182670

  18. 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

  19. 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.

  20. 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

  1. Development of electronic potential and current transducers suitable for gas insulated switchgear and adequate for application to substation digital control systems

    SciTech Connect

    Tokoro, K.; Harumoto, Y.; Ida, Y.; Mukae, H.; Ohno, Y.; Shimada, M.; Yamamoto, H.; Yoshida, Y.

    1982-10-01

    Substation Digital Control System (SDCS) had been developed for the future system controlling the large scale power system. For application of SDCS to Gas Insulated Switchgear (GIS), electronic potential and current transducers fit for GIS have been developed. This equipment is composed of a capacitive dividing type potential transducer, a low burden current transformer, an analogue-to-digital conversion unit and an optical fiber signal transmit system. Good performance is confirmed by the application tests simulating the field circumstances.

  2. Mitochondrial DNA control region sequence variation suggests an independent origin of an {open_quotes}Asian-specific{close_quotes} 9-bp deletion in Africans

    SciTech Connect

    Soodyall, H.; Redd, A.; Vigilant

    1994-09-01

    The intergenic noncoding region between the cytochrome oxidase II and lysyl tRNA genes of human mitochondrial DNA (mtDNA) is associated with two tandemly arranged copies of a 9-bp sequence. A deletion of one of these repeats has been found at varying frequencies in populations of Asian descent, and is commonly referred to as an {open_quotes}Asian-specific{close_quotes} marker. We report here that the 9-bp deletion is also found at a frequency of 10.2% (66/649) in some indigenous African populations, with frequencies of 28.6% (20/70) in Pygmies, 26.6% (12/45) in Malawians and 15.4% (31/199) in southeastern Bantu-speaking populations. The deletion was not found in 123 Khoisan individuals nor in 209 western Bantu-speaking individuals, with the exception of 3 individuals from one group that was admixed with Pygmies. Sequence analysis of the two hypervariable segments of the mtDNA control region reveals that the types associated with the African 9-bp deletion are different from those found in Asian-derived populations with the deletion. Phylogenetic analysis separates the {open_quotes}African{close_quotes} and {open_quotes}Asian{close_quotes} 9-bp deletion types into two different clusters which are statistically supported. Mismatch distributions based on the number of differences between pairs of mtDNA types are consistent with this separation. These findings strongly support the view that the 9-bp deletion originated independently in Africa and in Asia.

  3. 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

  4. Cell type-specific control of protein synthesis and proliferation by FGF-dependent signaling to the translation repressor 4E-BP.

    PubMed

    Ruoff, Rachel; Katsara, Olga; Kolupaeva, Victoria

    2016-07-01

    Regulation of protein synthesis plays a vital role in posttranscriptional modulation of gene expression. Translational control most commonly targets the initiation of protein synthesis: loading 40S ribosome complexes onto mRNA and AUG start codon recognition. This step is initiated by eukaryotic initiation factor 4E (eIF4E) (the m7GTP cap-binding protein), whose binding to eIF4G (a scaffolding subunit) and eIF4A (an ATP-dependent RNA helicase) leads to assembly of active eIF4F complex. The ability of eIF4E to recognize the cap is prevented by its binding to eIF4E binding protein (4E-BP), which thereby inhibits cap-dependent translation by sequestering eIF4E. The 4E-BP activity is, in turn, inhibited by mTORC1 [mTOR (the mechanistic target of rapamycin) complex 1] mediated phosphorylation. Here, we define a previously unidentified mechanism of mTOR-independent 4E-BP1 regulation that is used by chondrocytes upon FGF signaling. Chondrocytes are responsible for the formation of the skeleton long bones. Unlike the majority of cell types where FGF signaling triggers proliferation, chondrocytes respond to FGF with inhibition. We establish that FGF specifically suppresses protein synthesis in chondrocytes, but not in any other cells of mesenchymal origin. Furthermore, 4E-BP1 repressor activity is necessary not only for suppression of protein synthesis, but also for FGF-induced cell-cycle arrest. Importantly, FGF-induced changes in the 4E-BP1 activity observed in cell culture are likewise detected in vivo and reflect the action of FGF signaling on downstream targets during bone development. Thus, our findings demonstrate that FGF signaling differentially impacts protein synthesis through either stimulation or repression, in a cell-type-dependent manner, with 4E-BP1 being a key player. PMID:27313212

  5. Climate controls on savanna C3 and C4 expansion in Southern Africa during the last 36 kyr BP

    NASA Astrophysics Data System (ADS)

    Wang, Y. V.; Larsen, T.; Andersen, N.; Blanz, T.; Schneider, R. R.

    2010-12-01

    Savannahs contain a mixture of C3 and C4 vegetation, accounting for more than a quarter of global primary production and are the second most important biome on the continents. However, our understanding on how savannahs will respond to rising CO2 concentration and temperatures or the IPCC estimated decrease in rainfall is not yet clear in spite of potential far reaching socio-economic consequences. In this study, we used the δD and δ13C of sedimentary long-chain n-alkanes (n-C27,29,31,33 ) in concert with reconstructions for sea surface temperatures and fluvial discharge from a marine sediment core (GIK16160-3, 18°14.47’S, 37°52.27’W, 1334m water depth), collected near the Zambezi river mouth to examine savannah responses under different hydrological and climate conditions in Southern Africa during the last 36 kyr BP. Our data show large variability in both δD and δ13C records of the four n-alkanes, with isotopic differences between individual n-alkanes being far more pronounced during the Glacial than during the Deglacial and Holocene. These large differences may be explained by proportionally higher contributions of C4 grasses over C3 trees to the n-C33,31, which seems to be opposite for n-C29. A strong anticorrelation between δD and δ13C from 36 to 16 kyr BP for n-C31 (R2=0.55) and n-C33 (R2=0.70) suggests that δD of these n-alkanes is strongly influenced by changes in vegetation types as well as physiological effects, rather than being directly related to evaporation/ precipitation balance. In contrast, no apparent relationship (R2=0.32) exists between δD and δ13C of n-C29, suggesting that n-C29 is the most promising hydrological proxy due to less variable vegetation type contributions to n-C29 throughout the core. The C4 plant contribution, which was estimated by taking into account the four n-alkanes δ13C signals and their abundance, implies dominance of C4 grass between 36 and 20 kyr BP, and more evenly distributed C3 and C4 vegetation from

  6. 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

  7. 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 716.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.25 Adequate file search. The scope of...

  8. 29 CFR 98.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Adequate evidence. 98.900 Section 98.900 Labor Office of the Secretary of Labor GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 98.900 Adequate evidence. Adequate evidence means information sufficient to support the reasonable belief that a...

  9. The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression.

    PubMed

    Male, Victoria; Nisoli, Ilaria; Kostrzewski, Tomasz; Allan, David S J; Carlyle, James R; Lord, Graham M; Wack, Andreas; Brady, Hugh J M

    2014-04-01

    The transcription factor E4bp4 (Nfil3) is essential for natural killer (NK) cell production. Here, we show that E4bp4 is required at the NK lineage commitment point when NK progenitors develop from common lymphoid progenitors (CLPs) and that E4bp4 must be expressed at the CLP stage for differentiation toward the NK lineage to occur. To elucidate the mechanism by which E4bp4 promotes NK development, we identified a central core of transcription factors that can rescue NK production from E4bp4(-/-) progenitors, suggesting that they act downstream of E4bp4. Among these were Eomes and Id2, which are expressed later in development than E4bp4. E4bp4 binds directly to the regulatory regions of both Eomes and Id2, promoting their transcription. We propose that E4bp4 is required for commitment to the NK lineage and promotes NK development by directly regulating the expression of the downstream transcription factors Eomes and Id2. PMID:24663216

  10. Elevated BP after AKI.

    PubMed

    Hsu, Chi-Yuan; Hsu, Raymond K; Yang, Jingrong; Ordonez, Juan D; Zheng, Sijie; Go, Alan S

    2016-03-01

    The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP-defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit-during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization. PMID:26134154

  11. [Dynamic behavior of the adaptive control system, hypothalamus--anterior pituitary--adrenal cortex. Animal experimental study of the adequate system dynamics of the direct and indirect parameters of the adaptive control system].

    PubMed

    Zintzsch, I; Seidel, H; Lantzsch, C; Lantzsch, M

    1979-01-01

    The dynamic response of the adaptive closed-loop control system hypothalamus-anterior pituitary-adrenal cortex after application of short-time disturb pulses were examined experimentally in the pig. Blood sampling was performed biologically non-reactive by chronically implanted vascular catheters in the upper vena cava. A circadian biphase periodical dynamics characterizes the distrubance response of the adaptive control system, respectively, its direct and indirect parameters. After distrubance variables induced initial excess the plasma corticosteriods undershoot the basic level over a long period. Conversely, the dynamics of the eosinophils is determined through an initial eosinopenic phase and a subsequent typical overshoot. Periodical dynamic is absent in the steady state. The controller of the adaptive system does not show any spontaneous activity in the steady state without stress. The absence of an endogenic periodicity of the dependent parameters likewise gives evidence of an active oscillator. On the other hand, the controlling unit of the adaptive system constitutes a control response of circadian periodicty after activation by disturbance variables in pulse shape. The high damping of the control system terminates the transient state within 24 hours, and the corticosteriods and the eosinophils reach the steady state level. This control quality of the adaptive control system gains a high importance in the origination of the spontaneous circadian periodicity by corticosteriods and eosinophils and for the biological compensation of exogenous distrubance variables. PMID:233184

  12. 34 CFR 85.900 - Adequate evidence.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) Definitions § 85.900 Adequate evidence. Adequate evidence means information sufficient to support the reasonable belief that a particular act or omission has occurred. Authority: E.O. 12549 (3 CFR, 1986 Comp., p. 189); E.O 12689 (3 CFR, 1989 Comp., p. 235); 20 U.S.C. 1082, 1094, 1221e-3 and 3474; and Sec....

  13. 29 CFR 452.110 - Adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Adequate safeguards. 452.110 Section 452.110 Labor... DISCLOSURE ACT OF 1959 Election Procedures; Rights of Members § 452.110 Adequate safeguards. (a) In addition to the election safeguards discussed in this part, the Act contains a general mandate in section...

  14. 29 CFR 452.110 - Adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 2 2011-07-01 2011-07-01 false Adequate safeguards. 452.110 Section 452.110 Labor... DISCLOSURE ACT OF 1959 Election Procedures; Rights of Members § 452.110 Adequate safeguards. (a) In addition to the election safeguards discussed in this part, the Act contains a general mandate in section...

  15. 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.

  16. Association analysis of IGF2BP2, KCNJ11, and CDKAL1 polymorphisms with type 2 diabetes mellitus in a Moroccan population: a case-control study and meta-analysis.

    PubMed

    Benrahma, Houda; Charoute, Hicham; Lasram, Khaled; Boulouiz, Redouane; Atig, Rym Kefi-Ben; Fakiri, Malika; Rouba, Hassan; Abdelhak, Sonia; Barakat, Abdelhamid

    2014-10-01

    Associations with type 2 diabetes mellitus have been identified for variants CDKAL1 rs7756992, KCNJ11 rs5219, and IGF2BP2 rs4402960 in different populations. In a case-control study of 250 unrelated Moroccan diabetic patients and 250 healthy controls, we used TaqMan allelic discrimination assays to genotype the three SNPs and meta-analysis to investigate the association between the polymorphisms and diabetes in Arab populations. The results showed a significant diabetes association only with the variant rs4402960 of the IGF2BP2 gene under additive 2 (GG vs. TT; p = 0.009) and recessive (TT vs. GG+GT; p = 0.003) models. Meta-analysis indicated significant association between the IGF2BP2 rs4402960 and CDKAL1 rs7756992 polymorphisms and increased risk of diabetes in Arab populations. According to our results, the case-control study and meta-analysis revealed a significant association between the IGF2BP2 rs4402960 variant and type 2 diabetes in Moroccan and Arab populations. PMID:24898818

  17. 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...

  18. Americans Getting Adequate Water Daily, CDC Finds

    MedlinePlus

    ... medlineplus/news/fullstory_158510.html Americans Getting Adequate Water Daily, CDC Finds Men take in an average ... new government report finds most are getting enough water each day. The data, from the U.S. National ...

  19. Americans Getting Adequate Water Daily, CDC Finds

    MedlinePlus

    ... gov/news/fullstory_158510.html Americans Getting Adequate Water Daily, CDC Finds Men take in an average ... new government report finds most are getting enough water each day. The data, from the U.S. National ...

  20. Blood pressure (BP) assessment-from BP level to BP variability.

    PubMed

    Feber, Janusz; Litwin, Mieczyslaw

    2016-07-01

    The assessment of blood pressure (BP) can be challenging in children, especially in very young individuals, due to their variable body size and lack of cooperation. In the absence of data relating BP with cardiovascular outcomes in children, there is a need to convert absolute BP values (in mmHg) into age-, gender- and height appropriate BP percentiles or Z-scores in order to compare a patient's BP with the BP of healthy children of the same age, but also of children of different ages. Traditionally, the interpretation of BP has been based mainly on the assessment of the BP level obtained by office, home or 24-h BP monitoring. Recent studies suggest that it is not only BP level (i.e. average BP) but also BP variability that is clinically important for the development of target organ damage, including the progression of chronic kidney disease. In this review we describe current methods to evaluate of BP level, outline available methods for BP variability assessment and discuss the clinical consequences of BP variability, including its potential role in the management of hypertension. PMID:26201477

  1. Adequate supervision for children and adolescents.

    PubMed

    Anderst, James; Moffatt, Mary

    2014-11-01

    Primary care providers (PCPs) have the opportunity to improve child health and well-being by addressing supervision issues before an injury or exposure has occurred and/or after an injury or exposure has occurred. Appropriate anticipatory guidance on supervision at well-child visits can improve supervision of children, and may prevent future harm. Adequate supervision varies based on the child's development and maturity, and the risks in the child's environment. Consideration should be given to issues as wide ranging as swimming pools, falls, dating violence, and social media. By considering the likelihood of harm and the severity of the potential harm, caregivers may provide adequate supervision by minimizing risks to the child while still allowing the child to take "small" risks as needed for healthy development. Caregivers should initially focus on direct (visual, auditory, and proximity) supervision of the young child. Gradually, supervision needs to be adjusted as the child develops, emphasizing a safe environment and safe social interactions, with graduated independence. PCPs may foster adequate supervision by providing concrete guidance to caregivers. In addition to preventing injury, supervision includes fostering a safe, stable, and nurturing relationship with every child. PCPs should be familiar with age/developmentally based supervision risks, adequate supervision based on those risks, characteristics of neglectful supervision based on age/development, and ways to encourage appropriate supervision throughout childhood. PMID:25369578

  2. 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…

  3. 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…

  4. Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

    PubMed Central

    Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

    2013-01-01

    In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

  5. Noninvasive ambulatory blood pressure control in normotensive pregnant women.

    PubMed

    Margulies, M; Zin, C; Margulies, N D; Voto, L S

    1989-12-01

    Twenty-four hour noninvasive, automatic and ambulatory control of blood pressure (BP) was carried out on 11 normotensive pregnant women in the third trimester of pregnancy with a Del Mar Avionics Model 1978 Pressurometer III System at 7.5 min intervals during 24 h. The patients kept a detailed record of their activities during those 24 h. BP increased from 9 AM to a peak between 7 and 10 PM. Mean (+/- SD) waking and sleeping values were 110.56 +/- 6.68 mm Hg and 96.5 +/- 10.01 mm Hg, respectively, for systolic BP, and 71.41 +/- 5.35 mm Hg and 62.82 +/- 5.47 mm Hg, respectively, for diastolic BP. There was a significant difference in systolic and diastolic BP between sleeping hours and waking hours. We believe that 24-h control of BP behavior in normotensive pregnant women allows us to adequately diagnose hypertensive disease in pregnancy. PMID:2610998

  6. The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review

    PubMed Central

    Cox, Devin M.; Butler, Merlin G.

    2015-01-01

    Patients with the 15q11.2 BP1–BP2 microdeletion can present with developmental and language delay, neurobehavioral disturbances and psychiatric problems. Autism, seizures, schizophrenia and mild dysmorphic features are less commonly seen. The 15q11.2 BP1–BP2 microdeletion involving four genes (i.e., TUBGCP5, CYFIP1, NIPA1, NIPA2) is emerging as a recognized syndrome with a prevalence ranging from 0.57%–1.27% of patients presenting for microarray analysis which is a two to four fold increase compared with controls. Review of clinical features from about 200 individuals were grouped into five categories and included developmental (73%) and speech (67%) delays; dysmorphic ears (46%) and palatal anomalies (46%); writing (60%) and reading (57%) difficulties, memory problems (60%) and verbal IQ scores ≤75 (50%); general behavioral problems, unspecified (55%) and abnormal brain imaging (43%). Other clinical features noted but not considered as common were seizures/epilepsy (26%), autism spectrum disorder (27%), attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD) (35%), schizophrenia/paranoid psychosis (20%) and motor delay (42%). Not all individuals with the deletion are clinically affected, yet the collection of findings appear to share biological pathways and presumed genetic mechanisms. Neuropsychiatric and behavior disturbances and mild dysmorphic features are associated with genomic imbalances of the 15q11.2 BP1–BP2 region, including microdeletions, but with an apparent incomplete penetrance and variable expressivity. PMID:25689425

  7. 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. PMID:9670174

  8. 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

  9. Transcriptional Regulation of CRD-BP by c-myc

    PubMed Central

    Noubissi, Felicite K.; Nikiforov, Mikhail A.; Colburn, Nancy; Spiegelman, Vladimir S.

    2010-01-01

    The coding region determinant binding protein, CRD-BP, is a multifunctional RNA binding protein involved in different processes such as mRNA turnover, translation control, and localization. It is mostly expressed in fetal and neonatal tissues, where it regulates many transcripts essential for normal embryonic development. CRD-BP is scarce or absent in normal adult tissues but reactivated and/or overexpressed in various neoplastic and preneoplastic tumors and in most cell lines. Its expression has been associated with the most aggressive form of some cancers. CRD-BP is an important regulator of different genes including a variety of oncogenes or proto-oncogenes (c-myc, β-TrCP1, GLI1, etc.). Regulation of CRD-BP expression is critical for proper control of its targets as its overexpression may play an important role in abnormal cell proliferation, suppression of apoptosis, invasion, and metastasis. Molecular bases of the regulatory mechanisms governing CRD-BP expression are still not completely elucidated. In this article, we have identified c-myc as a novel transcriptional regulator of CRD-BP. We show that c-myc binds to CRD-BP promoter and induces its transcription. This induction of CRD-BP expression contributes to the role of c-myc in the regulation of translation, increase in cell size, and acceleration of cell cycle progression via a mechanism involving upregulation of β-TrCP1 levels and activities and accelerated degradation of PDCD4. PMID:21779431

  10. 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...

  11. 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...

  12. 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...) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use. Adequate directions for use means directions under which the layman can use a drug safely and for the purposes...

  13. 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...) DRUGS: GENERAL LABELING General Labeling Provisions § 201.5 Drugs; adequate directions for use. Adequate directions for use means directions under which the layman can use a drug safely and for the purposes...

  14. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Responsibility for maintaining adequate safeguards. 200.14 Section 200.14 Accounts RECOVERY ACCOUNTABILITY AND TRANSPARENCY BOARD PRIVACY ACT OF 1974 § 200.14 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining adequate technical, physical, and...

  15. 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 adequate technical, physical, and security...

  16. 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 adequate technical, physical, and security...

  17. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 4 Accounts 1 2011-01-01 2011-01-01 false Responsibility for maintaining adequate safeguards. 200....14 Responsibility for maintaining adequate safeguards. The Board has the responsibility for maintaining adequate technical, physical, and security safeguards to prevent unauthorized disclosure...

  18. BP details new recycling process

    SciTech Connect

    Chynoweth, E.

    1992-04-22

    BP Chemicals (London) is developing a preprocessing thermal cracker for recycling mixed plastics waste as an add-on to existing petrochemicals or refinery complexes. The company is currently discussing the technology with other plastic producers to {open_quotes}move forward together,{close_quotes} say Serge Huybrechts, branch R&D manager at BP Chemicals at Grangemouth. He says the unit would be able to deliver an intermediate feed of similar composition to chemical naphtha for chemical or refinery processes including steam cracking, catalytic cracking, coking, gasification, and hydrocracking. In comparison, pyrolysis gives a range of products, from light gas to heavy aromatics, that are difficult to integrate into existing equipment.

  19. 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

  20. Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial

    PubMed Central

    McManus, Richard J; Roalfe, Andrea; Fletcher, Kate; Taylor, Clare J; Martin, Una; Virdee, Satnam; Greenfield, Sheila; Hobbs, F D Richard

    2016-01-01

    Objective To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. Design Open label randomised controlled trial. Setting 99 general practices in England, with participants recruited in 2009-11. Participants People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. Interventions Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. Main outcome measure Change in systolic blood pressure between baseline and 12 months. Results 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). Conclusions Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure. Trial registration Current Controlled Trials ISRCTN29062286. PMID:26919870

  1. Two Self-management Interventions to Improve Hypertension Control: A Randomized Trial

    PubMed Central

    Bosworth, Hayden B.; Olsen, Maren K.; Grubber, Janet M.; Neary, Alice M.; Orr, Melinda M.; Powers, Benjamin J.; Adams, Martha B.; Svetkey, Laura P.; Reed, Shelby D.; Li, Yanhong; Dolor, Rowena J.; Oddone, Eugene Z.

    2010-01-01

    Background Less than 40% of Americans with hypertension have adequate blood pressure (BP) control. Objectives To compare two self-management interventions for improving BP control among hypertensive patients. Design A 2 by 2 randomized trial stratified by enrollment site and patient literacy status with two-year follow-up (5/2004-1/2008). Setting Two university-affiliated primary care clinics. Patients 636 patients were randomized (31% recruitment rate) among the 2060 eligible hypertensive patients. Interventions Research assistants randomized eligible patients via a centralized blinded and stratified randomization algorithm to receive either: 1) usual care; 2) bi-monthly tailored nurse-administered telephone intervention targeting hypertension-related behaviors; 3) BP monitoring consisting of measuring BP three times per week, or; 4) a combination of the two interventions. Measurements The primary outcome was BP control evaluated at six-month intervals over 24 months. 475 (75%) completed the 24-month BP follow-up. Results Improvements in proportion of BP control for the intervention groups relative to the usual care group at 24 months were: behavioral group, 4.3% (95% CI: −4.5%, 12.9); home BP monitoring group, 7.6% (95% CI: −1.9%, 17.0%); and, combined interventions, 11.0% (95% CI: 1.9%, 19.8%). For systolic BP, relative to usual care, the 24 month difference was, +0.6 mmHg (95% CI: −2.2, 3.4) for the behavioral intervention group, −0.6 mmHg (95% CI: −3.6, 2.3) for the home monitoring group, and −3.9 mmHg (95% CI: −6.9, −0.9) for the combined interventions. Similar patterns were observed for diastolic BP at 24 months. Limitations Changes in medication use and diet were only monitored in intervention participants; 25% lacked 24 month outcome data; 73% had adequate BP control at baseline; the study setting was an academic health center, all factors that potentially limit generalizability. Conclusion Combined home BP monitoring and tailored

  2. Prevalence of the 4977-bp and 4408-bp mitochondrial DNA deletions in mesenteric arteries from patients with colorectal cancer.

    PubMed

    Li, Tao; Chen, Gui-Lan; Lan, Huan; Mao, Liang; Zeng, Bo

    2016-09-01

    Mitochondrial DNA (mtDNA) deletions are found in many diseased tissues and lead to impairment of mitochondrial functions. In this study, we found wide presence of the common 4977-bp and a novel 4408-bp deletion in the mtDNA of mesenteric arteries from patients with colorectal cancer. These two deletions were also detected in samples from healthy individuals. The content of mtDNA with the 4977-bp deletion was significantly lower in healthy controls than cancer-associated samples, and there was no significant difference for the 4408-bp deletion between the two groups. These results suggest that mtDNA in blood vessels around cancer cells may be strongly affected by oxidative stress and tend to accumulate more large-scale variations. PMID:26332461

  3. 7 CFR 4290.200 - Adequate capital for RBICs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 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...

  4. 13 CFR 107.200 - Adequate capital for Licensees.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Adequate capital for Licensees... INVESTMENT COMPANIES Qualifying for an SBIC License Capitalizing An Sbic § 107.200 Adequate capital for... Licensee, and to receive Leverage. (a) You must have enough Regulatory Capital to provide...

  5. 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... INVESTMENT COMPANIES Qualifying for an SBIC License Capitalizing An Sbic § 107.200 Adequate capital for... Licensee, and to receive Leverage. (a) You must have enough Regulatory Capital to provide...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 10 CFR 503.35 - Inability to obtain adequate capital.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Inability to obtain adequate capital. 503.35 Section 503.35 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS NEW FACILITIES Permanent Exemptions for New Facilities § 503.35 Inability to obtain adequate capital. (a) Eligibility. Section 212(a)(1)(D)...

  19. 10 CFR 503.35 - Inability to obtain adequate capital.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Inability to obtain adequate capital. 503.35 Section 503.35 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS NEW FACILITIES Permanent Exemptions for New Facilities § 503.35 Inability to obtain adequate capital. (a) Eligibility. Section 212(a)(1)(D)...

  20. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must find... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Adequate exploration plan....

  1. 15 CFR 970.404 - Adequate exploration plan.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Certification of Applications § 970.404 Adequate exploration plan. Before he may certify an application, the Administrator must find... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Adequate exploration plan....

  2. "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…

  3. 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

  4. 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

  5. Arabidopsis: An Adequate Model for Dicot Root Systems?

    PubMed

    Zobel, Richard W

    2016-01-01

    The Arabidopsis root system is frequently considered to have only three classes of root: primary, lateral, and adventitious. Research with other plant species has suggested up to eight different developmental/functional classes of root for a given plant root system. If Arabidopsis has only three classes of root, it may not be an adequate model for eudicot plant root systems. Recent research, however, can be interpreted to suggest that pre-flowering Arabidopsis does have at least five (5) of these classes of root. This then suggests that Arabidopsis root research can be considered an adequate model for dicot plant root systems. PMID:26904040

  6. Is the Marketing Concept Adequate for Continuing Education?

    ERIC Educational Resources Information Center

    Rittenburg, Terri L.

    1984-01-01

    Because educators have a social responsibility to those they teach, the marketing concept may not be adequate as a philosophy for continuing education. In attempting to broaden the audience for continuing education, educators should consider a societal marketing concept to meet the needs of the educationally disadvantaged. (SK)

  7. 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…

  8. 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 AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY INSPECTION AND CERTIFICATION...

  9. 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.…

  10. 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…

  11. 34 CFR 200.13 - Adequate yearly progress in general.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 1 2011-07-01 2011-07-01 false Adequate yearly progress in general. 200.13 Section 200.13 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE...

  12. 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 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF EDUCATION TITLE I-IMPROVING THE ACADEMIC ACHIEVEMENT OF THE DISADVANTAGED...

  13. 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…

  14. 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

  15. 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. PMID:26454118

  16. 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.

  17. Maintaining adequate hydration and nutrition in adult enteral tube feeding.

    PubMed

    Dunn, Sasha

    2015-01-01

    Predicting the nutritional and fluid requirements of enterally-fed patients can be challenging and the practicalities of ensuring adequate delivery must be taken into consideration. Patients who are enterally fed can be more reliant on clinicians, family members and carers to meet their nutrition and hydration needs and identify any deficiencies, excesses or problems with delivery. Estimating a patient's requirements can be challenging due to the limitations of using predictive equations in the clinical setting. Close monitoring by all those involved in the patient's care, as well as regular review by a dietitian, is therefore required to balance the delivery of adequate feed and fluids to meet each patient's individual needs and prevent the complications of malnutrition and dehydration. Increasing the awareness of the signs of malnutrition and dehydration in patients receiving enteral tube feeding among those involved in a patient's care will help any deficiencies to be detected early on and rectified before complications occur. PMID:26087203

  18. Assessing juvenile sex offenders to determine adequate levels of supervision.

    PubMed

    Gerdes, K E; Gourley, M M; Cash, M C

    1995-08-01

    The present study analyzed the internal consistency of four inventories currently being used by probation officers in the state of Utah to determine adequate and efficacious supervision levels and placement for juvenile sex offenders. The internal consistency or reliability of the inventories ranged from moderate to good. Factor analysis was utilized to significantly increase the reliability of the four inventories by collapsing them into the following three factors: (a) Custodian's and Juvenile's Attitude Toward Intervention; (b) Offense Characteristics; and (c) Historical Risk Factors. These three inventories/factors explained 41.2% of the variance in the combined inventories' scores. Suggestions are made regarding the creation of an additional inventory. "Characteristics of the Victim" to account for more of the variance. In addition, suggestions as to how these inventories can be used by probation officers to make objective and consistent decisions about adequate supervision levels and placement for juvenile sex offenders are discussed. PMID:7583754

  19. 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.

  20. Adequation of mini satellites to oceanic altimetry missions

    NASA Astrophysics Data System (ADS)

    Bellaieche, G.; Aguttes, J. P.

    1993-01-01

    Association of the mini satellite concept and oceanic altimetry missions is discussed. Mission definition and most constraining requirements (mesoscale for example) demonstrate mini satellites to be quite adequate for such missions. Progress in altimeter characteristics, orbit determination, and position reporting allow consideration of oceanic altimetry missions using low Earth orbit satellites. Satellite constellation, trace keeping and orbital period, and required payload characteristics are exposed. The mission requirements covering Sun synchronous orbit, service area, ground system, and launcher characteristics as well as constellation maintenance strategy are specified. Two options for the satellite, orbital mechanics, propulsion, onboard power and stabilizing subsystems, onboard management, satellite ground linkings, mechanical and thermal subsystems, budgets, and planning are discussed.

  1. 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

  2. TopBP1 deficiency impairs V(D)J recombination during lymphocyte development

    PubMed Central

    Kim, Jieun; Kyu Lee, Sung; Jeon, Yoon; Kim, Yehyun; Lee, Changjin; Ho Jeon, Sung; Shim, Jaegal; Kim, In-Hoo; Hong, Seokmann; Kim, Nayoung; Lee, Ho; Seong, Rho Hyun

    2014-01-01

    TopBP1 was initially identified as a topoisomerase II-β-binding protein and it plays roles in DNA replication and repair. We found that TopBP1 is expressed at high levels in lymphoid tissues and is essential for early lymphocyte development. Specific abrogation of TopBP1 expression resulted in transitional blocks during early lymphocyte development. These defects were, in major part, due to aberrant V(D)J rearrangements in pro-B cells, double-negative and double-positive thymocytes. We also show that TopBP1 was located at sites of V(D)J rearrangement. In TopBP1-deficient cells, γ-H2AX foci were found to be increased. In addition, greater amount of γ-H2AX product was precipitated from the regions where TopBP1 was localized than from controls, indicating that TopBP1 deficiency results in inefficient DNA double-strand break repair. The developmental defects were rescued by introducing functional TCR αβ transgenes. Our data demonstrate a novel role for TopBP1 as a crucial factor in V(D)J rearrangement during the development of B, T and iNKT cells. PMID:24442639

  3. 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.

  4. Purchasing a cycle helmet: are retailers providing adequate advice?

    PubMed Central

    Plumridge, E.; McCool, J.; Chetwynd, J.; Langley, J. D.

    1996-01-01

    OBJECTIVES: The aim of this study was to examine the selling of cycle helmets in retail stores with particular reference to the adequacy of advice offered about the fit and securing of helmets. METHODS: All 55 retail outlets selling cycle helmets in Christchurch, New Zealand were studied by participant observation. A research entered each store as a prospective customer and requested assistance to purchase a helmet. She took detailed field notes of the ensuing encounter and these were subsequently transcribed, coded, and analysed. RESULTS: Adequate advice for helmet purchase was given in less than half of the stores. In general the sales assistants in specialist cycle shops were better informed and gave more adequate advice than those in department stores. Those who have good advice also tended to be more good advice also tended to be more active in helping with fitting the helmet. Knowledge about safety standards was apparent in one third of sales assistants. Few stores displayed information for customers about the correct fit of cycle helmets. CONCLUSIONS: These findings suggest that the advice and assistance being given to ensure that cycle helmets fit properly is often inadequate and thus the helmets may fail to fulfil their purpose in preventing injury. Consultation between retailers and policy makers is a necessary first step to improving this situation. PMID:9346053

  5. Adequate drainage system design for heap leaching structures.

    PubMed

    Majdi, Abbas; Amini, Mehdi; Nasab, Saeed Karimi

    2007-08-17

    The paper describes an optimum design of a drainage system for a heap leaching structure which has positive impacts on both mine environment and mine economics. In order to properly design a drainage system the causes of an increase in the acid level of the heap which in turn produces severe problems in the hydrometallurgy processes must be evaluated. One of the most significant negative impacts induced by an increase in the acid level within a heap structure is the increase of pore acid pressure which in turn increases the potential of a heap-slide that may endanger the mine environment. In this paper, initially the thickness of gravelly drainage layer is determined via existing empirical equations. Then by assuming that the calculated thickness is constant throughout the heap structure, an approach has been proposed to calculate the required internal diameter of the slotted polyethylene pipes which are used for auxiliary drainage purposes. In order to adequately design this diameter, the pipe's cross-sectional deformation due to stepped heap structure overburden pressure is taken into account. Finally, a design of an adequate drainage system for the heap structure 2 at Sarcheshmeh copper mine is presented and the results are compared with those calculated by exiting equations. PMID:17321044

  6. Constitutive expression of transgenes encoding derivatives of the synthetic antimicrobial peptide BP100: impact on rice host plant fitness

    PubMed Central

    2012-01-01

    example, BP100 based on inverted repeats, have adequate agronomic performance and resistant phenotypes as a result of a complex equilibrium between bp100der toxicity to plant cells, antimicrobial activity and transgene-derived plant stress response. It is likely that these results can be extended to other peptides with similar characteristics. PMID:22947243

  7. Are PPS payments adequate? Issues for updating and assessing rates

    PubMed Central

    Sheingold, Steven H.; Richter, Elizabeth

    1992-01-01

    Declining operating margins under Medicare's prospective payment system (PPS) have focused attention on the adequacy of payment rates. The question of whether annual updates to the rates have been too low or cost increases too high has become important. In this article we discuss issues relevant to updating PPS rates and judging their adequacy. We describe a modification to the current framework for recommending annual update factors. This framework is then used to retrospectively assess PPS payment and cost growth since 1985. The preliminary results suggest that current rates are more than adequate to support the cost of efficient care. Also discussed are why using financial margins to evaluate rates is problematic and alternative methods that might be employed. PMID:10127450

  8. The adaptor 3BP2 is required for KIT receptor expression and human mast cell survival

    PubMed Central

    Ainsua-Enrich, Erola; Serrano-Candelas, Eva; Álvarez-Errico, Damiana; Picado, César; Sayós, Joan; Rivera, Juan; Martín, Margarita

    2015-01-01

    3BP2 is a cytoplasmic adaptor protein that acts as a positive regulator in mast cell FcεRI-dependent signaling. The KIT receptor whose ligand is the stem cell factor (SCF) is necessary for mast cell development, proliferation and survival as well as for optimal IgE-dependent signal. Activating mutations in KIT have been associated with several diseases including mastocytosis. In the present work, we found that 3BP2 silencing impairs KIT signaling pathways, thus affecting PI3K and MAP kinase pathways in human mast cells from HMC-1, LAD2 (human mast cell lines) and CD34+-derived mast cells. Unexpectedly, silencing of 3BP2 reduces KIT expression in normal human mast cells as well as in HMC-1 cells where KIT is mutated, thus increasing cellular apoptosis and caspase 3/7 activity. 3BP2 silencing reduces KIT transcription expression levels. Interestingly, 3BP2 silencing decreased MITF expression, a transcription factor involved in KIT expression. Reconstitution of 3BP2 in knockdown cells leads to reversal of KIT expression as well as survival phenotype. Accordingly MITF reconstitution enhances KIT expression levels in 3BP2 silenced cells. Moreover, downregulation of KIT expression by miRNA221 overexpression or the proteasome inhibitor bortezomib also reduced 3BP2 and MITF expression. Furthermore, KIT tyrosine activity inhibition reduced 3BP2 and MITF expression, demonstrating again a tight and reciprocal relationship between these molecules. Taken together, our results show that 3BP2 regulates human mast cell survival and participates in KIT-mediated signal transduction by directly controlling KIT receptor expression, suggesting its potential as a therapeutic target in mast cell-mediated inflammatory diseases and deregulated KIT disorders. PMID:25810396

  9. 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

  10. 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.

  11. 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.

  12. Adequate peritoneal dialysis: theoretical model and patient treatment.

    PubMed

    Tast, C

    1998-01-01

    The objective of this study was to evaluate the relationship between adequate PD with sufficient weekly Kt/V (2.0) and Creatinine clearance (CCR) (60l) and necessary daily dialysate volume. This recommended parameter was the result of a recent multi-centre study (CANUSA). For this there were 40 patients in our hospital examined and compared in 1996, who carried out PD for at least 8 weeks and up to 6 years. These goals (CANUSA) are easily attainable in the early treatment of many individuals with a low body surface area (BSA). With higher BSA or missing RRF (Residual Renal Function) the daily dose of dialysis must be adjusted. We found it difficult to obtain the recommended parameters and tried to find a solution to this problem. The simplest method is to increase the volume or exchange rate. The most expensive method is to change from CAPD to APD with the possibility of higher volume or exchange rates. Selection of therapy must take into consideration: 1. patient preference, 2. body mass, 3. peritoneal transport rates, 4. ability to perform therapy, 5. cost of therapy and 6. risk of peritonitis. With this information in mind, an individual prescription can be formulated and matched to the appropriate modality of PD. PMID:10392062

  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. 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

  15. 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

  16. A Role for Anti-BP180 Autoantibodies in Chronic Rhinosinusitis

    PubMed Central

    Jeffe, Jill S.; Seshadri, Sudarshan; Hamill, Kevin J.; Huang, Julia He; Carter, Roderick; Suh, Lydia; Hulse, Kathryn; Norton, James; Conley, David B.; Chandra, Rakesh K.; Kern, Robert C.; Jones, Jonathan C.R.; Schleimer, Robert P.; Tan, Bruce K.

    2013-01-01

    Objectives CRS is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS. Study Design Case-control experimental study Methods The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time PCR, Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera. Results BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluoresence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (p<0.05). Conclusions BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS. PMID:24167818

  17. E4BP4 overexpression: a protective mechanism in CD4+ T cells from SLE patients.

    PubMed

    Zhao, Ming; Liu, Qian; Liang, Gongping; Wang, Litao; Luo, Shuangyan; Tang, Qian; Zhao, Hongjun; Su, Yuwen; Yung, Susan; Chan, Tak Mao; Lu, Qianjin

    2013-03-01

    Systemic lupus erythematosus (SLE) is a prototype autoimmune disease characterized by various immunological abnormalities, including dysregulated activation of T and B lymphocytes, which trigger autoantibody production and immune-complex deposition. E4BP4, also known as NFIL3, has emerged as a major transcription factor that regulates the development and function of immune cells in a number of lineages. E4BP4 has been shown to regulate cytokines expression, and its synthesis is in turn controlled by various cytokines. To date, the roles of E4BP4 in immune dysregulation and autoimmune disorders are unclear. In this study, we demonstrated that E4BP4 expression is increased in CD4(+) T cells isolated from patients with active systemic lupus erythematosus (SLE), especially in patients treated with glucocorticoid (GC). Increased expression of E4BP4 inhibited the activation and self-reactivity of T cells stimulated by anti-CD3/CD28 antibodies. In contrast, the self-reactivity was enhanced in CD4(+) T cells from SLE patients following E4BP4 gene silencing and the production of autoantibody was increased in autologous B cells. We further demonstrated that E4BP4 directly regulated CD40L expression by binding to the promoter region and altering histone acetylation and methylation of the CD40L loci. Taken together, our data provide evidence that E4BP4 can inhibit CD40L expression through epigenetic modifications in the promoter region of CD40L, thus negatively regulating self-reactivity of SLE CD4(+) T cells. Furthermore, our data demonstrate that overexpression of E4BP4 initiates a protective mechanism in SLE CD4(+) T cells, which may be a promising target in the therapy for SLE. PMID:23340290

  18. 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

  19. Asian-specific mitochondrial genome polymorphism (9-bp deletion) in Hungarian patients with mitochondrial disease.

    PubMed

    Pentelenyi, Klara; Remenyi, Viktoria; Gal, Aniko; Milley, Gyorgy Mate; Csosz, Aranka; Mende, Balazs Gusztav; Molnar, Maria Judit

    2016-05-01

    A 9-bp deletion of the mtDNA is known as an anthropological marker of people with East-Asian origin. This 9-bp mtDNA deletion was analyzed in 1073 Hungarians with suspected mitochondrial disease and in 468 healthy control individuals. Fourteen cases with the 9-bp deletion were found in the cohort of mitochondrial patients, and one individual from 468 controls. In six cases the 9-bp deletion was present together with pathogenic major deletions in the mitochondrial genome. In one patient we found a frame shift mutation in the D-loop region, and in another family a pathogenic m.8322 A > G mutation in the tRNA(Lys) gene. Although the 9-bp deletion is common in the populations of the Pacific region and Asia, it is present in the Hungarian population as well. This 9-bp deletion may induce instability of the mtDNA and may provoke the introduction of other pathogenic mutations. PMID:25242187

  20. 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

  1. 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.

  2. 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

  3. Genetic and morphological features of human iPSC-derived neurons with chromosome 15q11.2 (BP1-BP2) deletions

    PubMed Central

    Das, DK; Tapias, V; D’Aiuto, L; Chowdari, KV; Francis, L; Zhi, Y; Ghosh, Bhattacharjee A; Surti, U; Tischfield, J; Sheldon, M; Moore, JC; Fish, K; Nimgaonkar, V

    2015-01-01

    Background Copy number variation on chromosome 15q11.2 (BP1-BP2) causes deletion of CYFIP1, NIPA1, NIPA2 and TUBGCP5; it also affects brain structure and elevates risk for several neurodevelopmental disorders that are associated with dendritic spine abnormalities. In rodents, altered cyfip1 expression changes dendritic spine morphology, motivating analyses of human neuronal cells derived from iPSCs (iPSC-neurons). Methods iPSCs were generated from a mother and her offspring, both carrying the 15q11.2 (BP1-BP2) deletion, and a non-deletion control. Gene expression in the deletion region was estimated using quantitative real-time PCR assays. Neural progenitor cells (NPCs) and iPSC-neurons were characterized using immunocytochemistry. Results CYFIP1, NIPA1, NIPA2 and TUBGCP5 gene expression was lower in iPSCs, NPCs and iPSC-neurons from the mother and her offspring in relation to control cells. CYFIP1 and PSD95 protein levels were lower in iPSC-neurons derived from the CNV bearing individuals using Western blot analysis. At 10 weeks post-differentiation, iPSC-neurons appeared to show dendritic spines and qualitative analysis suggested that dendritic morphology was altered in 15q11.2 deletion subjects compared with control cells. Conclusions The 15q11.2 (BP1-BP2) deletion is associated with reduced expression of four genes in iPSC-derived neuronal cells; it may also be associated altered iPSC-neuron dendritic morphology. PMID:26528485

  4. 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).

  5. 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

  6. 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…

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries.

    PubMed

    Taniguchi, Ryosuke; Miura, Yutaka; Koyama, Hiroyuki; Chida, Tsukasa; Anraku, Yasutaka; Kishimura, Akihiro; Shigematsu, Kunihiro; Kataoka, Kazunori; Watanabe, Toshiaki

    2016-06-01

    In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis. PMID:27183493

  16. 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...

  17. 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... (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...

  18. 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... (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...

  19. 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... (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...

  20. 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... (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...

  1. 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...

  2. 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...

  3. 36 CFR 13.960 - Who determines when there is adequate snow cover?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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

  8. The CES-2-related transcription factor E4BP4 is an intrinsic regulator of motoneuron growth and survival.

    PubMed

    Junghans, Dirk; Chauvet, Sophie; Buhler, Emmanuelle; Dudley, Keith; Sykes, Toby; Henderson, Christopher E

    2004-09-01

    The regulation of neuronal growth and survival during development requires interplay between extrinsic and intrinsic factors. Among the latter, transcription factors play a key role. In the nematode, the transcription factor CES-2 predisposes neurosecretory motoneurons to death, whereas E4BP4 (NFIL3), one of its vertebrate homologs, regulates survival of pro-B lymphocytes. We show that E4BP4 is expressed by embryonic rat and chicken motoneurons in vivo, with levels being highest in neurons that survive the period of naturally occurring cell death. Overexpression of E4BP4 by electroporation of purified motoneurons in culture protected them almost completely against cell death triggered by removal of neurotrophic factors or activation of death receptors. Moreover, E4BP4 strongly enhanced neuronal cell size and axonal growth. Axons of motoneurons transfected with E4BP4 were 3.5-fold longer than control neurons grown on laminin; this effect required the activity of PI3 kinase. In vivo, overexpression of E4BP4 in chicken embryos reduced the number of dying motoneurons by 45%. Our results define E4BP4 as a novel intrinsic regulator of motoneuron growth and survival. Pathways regulated by E4BP4 are of potential interest both for understanding neuromuscular development and for promoting neuronal survival and regeneration in pathological situations. PMID:15306565

  9. The transcription factor E4BP4 is not required for extramedullary pathways of NK cell development.

    PubMed

    Crotta, Stefania; Gkioka, Annita; Male, Victoria; Duarte, João H; Davidson, Sophia; Nisoli, Ilaria; Brady, Hugh J M; Wack, Andreas

    2014-03-15

    NK cells contribute to antitumor and antiviral immunosurveillance. Their development in the bone marrow (BM) requires the transcription factor E4BP4/NFIL3, but requirements in other organs are less well defined. In this study, we show that CD3(-)NK1.1(+)NKp46(+)CD122(+) NK cells of immature phenotype and expressing low eomesodermin levels are found in thymus, spleen, and liver of E4BP4-deficient mice, whereas numbers of mature, eomesodermin(high) conventional NK cells are drastically reduced. E4BP4-deficient CD44(+)CD25(-) double-negative 1 thymocytes efficiently develop in vitro into NK cells with kinetics, phenotype, and functionality similar to wild-type controls, whereas no NK cells develop from E4BP4-deficient BM precursors. In E4BP4/Rag-1 double-deficient (DKO) mice, NK cells resembling those in Rag-1-deficient controls are found in similar numbers in the thymus and liver. However, NK precursors are reduced in DKO BM, and no NK cells develop from DKO BM progenitors in vitro. DKO thymocyte precursors readily develop into NK cells, but DKO BM transfers into nude recipients and NK cells in E4BP4/Rag-1/IL-7 triple-KO mice indicated thymus-independent NK cell development. In the presence of T cells or E4BP4-sufficient NK cells, DKO NK cells have a selective disadvantage, and thymic and hepatic DKO NK cells show reduced survival when adoptively transferred into lymphopenic hosts. This correlates with higher apoptosis rates and lower responsiveness to IL-15 in vitro. In conclusion, we demonstrate E4BP4-independent development of NK cells of immature phenotype, reduced fitness, short t1/2, and potential extramedullary origin. Our data identify E4BP4-independent NK cell developmental pathways and a role for E4BP4 in NK cell homeostasis. PMID:24534532

  10. 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

  11. Overcome of Carbon Catabolite Repression of Bioinsecticides Production by Sporeless Bacillus thuringiensis through Adequate Fermentation Technology.

    PubMed

    Ben Khedher, Saoussen; Jaoua, Samir; Zouari, Nabil

    2014-01-01

    The overcoming of catabolite repression, in bioinsecticides production by sporeless Bacillus thuringiensis strain S22 was investigated into fully controlled 3 L fermenter, using glucose based medium. When applying adequate oxygen profile throughout the fermentation period (75% oxygen saturation), it was possible to partially overcome the catabolite repression, normally occurring at high initial glucose concentrations (30 and 40 g/L glucose). Moreover, toxin production yield by sporeless strain S22 was markedly improved by the adoption of the fed-batch intermittent cultures technology. With 22.5 g/L glucose used into culture medium, toxin production was improved by about 36% when applying fed-batch culture compared to one batch. Consequently, the proposed fed-batch strategy was efficient for the overcome of the carbon catabolite repression. So, it was possible to overproduce insecticidal crystal proteins into highly concentrated medium. PMID:25309756

  12. 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

  13. 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.

  14. BpMADS4 has a central role in inflorescence initiation in silver birch (Betula pendula).

    PubMed

    Elo, Annakaisa; Lemmetyinen, Juha; Novak, Anu; Keinonen, Kaija; Porali, Ilkka; Hassinen, Minna; Sopanen, Tuomas

    2007-09-01

    Acceleration of flowering would be beneficial for breeding trees with a long juvenile phase; conversely, inhibition of flowering would prevent the spread of transgenes from the genetically modified trees. We have previously isolated and characterized several MADS genes from silver birch (Betula pendula Roth). In this study, we investigated the more detailed function of one of them, BpMADS4, a member of the APETALA1/FRUITFULL group of MADS genes. The expression of BpMADS4 starts at very early stage of the male and female inflorescence development and the activity is high in the apex of the developing inflorescence. Later, some expression is detected in the bracts and in the flower initials. Ectopic expression of BpMADS4 accelerates flowering dramatically in normally flowering clones and also in the early-flowering birch clone, in which the earliest line flowered about 11 days after rooting, when the saplings were only 3 cm high. The birches transformed with the BpMADS4 antisense construct showed remarkable delay in flowering and the number of flowering individuals was reduced. Two of the transformed lines did not show any signs of flower development during our 2-year study, whereas all the control plants formed inflorescences within 107 days. Our results show that BpMADS4 has a critical role in the initiation of birch inflorescence development and that BpMADS4 seems to be involved in the transition from vegetative to reproductive development. Therefore, BpMADS4 provides a promising tool for the genetic enhancement of forest trees. PMID:18251933

  15. Mitochondrial intergenic COII/tRNA(Lys) 9-bp deletion, a biomarker for hepatocellular carcinoma?

    PubMed

    Ren, Weihua; Li, Yawei; Li, Rui; Feng, Hongbo; Wu, Shuangting; Mao, Yuhui; Huang, Lei

    2016-07-01

    The COII/tRNA(Lys) intergenic 9-bp deletion is one of the most commonly studied human mitochondrial DNA (mtDNA) polymorphisms. It consists of the loss of one of two tandemly repeated copies of the sequence CCCCCTCTA from a non-coding region located between cytochrome oxidase II (COII) and tRNA(Lys) gene. Most recently, case-control studies have shown a positive association between this deletion with hepatocellular cancer. In this study, we first performed a detailed analysis between this deletion and clinical diseases; moreover, we took the phylogenetic approach to examine the pathogenicity status of 9-bp deletion. PMID:26017042

  16. 21 CFR 314.126 - Adequate and well-controlled studies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications..., such as spontaneous change in the course of the disease, placebo effect, or biased observation. The... evidence” to support the claims of effectiveness for new drugs. Therefore, the study report should...

  17. 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

  18. IGF2BP2 promotes colorectal cancer cell proliferation and survival through interfering with RAF-1 degradation by miR-195.

    PubMed

    Ye, Song; Song, Wei; Xu, Xiaogang; Zhao, Xinyi; Yang, Liu

    2016-06-01

    Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a post-transcriptional regulatory factor implicated in mRNA localization, stability, and translational control. However, the role of IGF2BP2 regulation in colorectal cancer (CRC) and its underlying mechanism remain elusive. In this study, we found that IGF2BP2 expression is markedly increased in CRC tissues. Notably, IGF2BP2 overexpression strikingly enhanced the proliferation and survival of CRC cells in vitro, whereas its shRNA-mediated silencing resulted in the opposite. Molecular function analyses revealed that IGF2BP2 regulates RAF1 expression through blocking its degradation by miR-195. These results identify IGF2BP2 as a post-transcriptional regulatory mRNA-binding factor that contributes to CRC carcinogenesis. PMID:27153315

  19. 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

  20. 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

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

    PubMed

    Thomas, Jean-Luc; Moncollin, Vincent; Ravel-Chapuis, Aymeric; Valente, Carmen; Corda, Daniela; Méjat, Alexandre; Schaeffer, Laurent

    2015-12-01

    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

  2. Palmitoylation regulates plasma membrane–nuclear shuttling of R7BP, a novel membrane anchor for the RGS7 family

    PubMed Central

    Drenan, Ryan M.; Doupnik, Craig A.; Boyle, Maureen P.; Muglia, Louis J.; Huettner, James E.; Linder, Maurine E.; Blumer, Kendall J.

    2005-01-01

    The RGS7 (R7) family of RGS proteins bound to the divergent Gβ subunit Gβ5 is a crucial regulator of G protein–coupled receptor (GPCR) signaling in the visual and nervous systems. Here, we identify R7BP, a novel neuronally expressed protein that binds R7–Gβ5 complexes and shuttles them between the plasma membrane and nucleus. Regional expression of R7BP, Gβ5, and R7 isoforms in brain is highly coincident. R7BP is palmitoylated near its COOH terminus, which targets the protein to the plasma membrane. Depalmitoylation of R7BP translocates R7BP–R7–Gβ5 complexes from the plasma membrane to the nucleus. Compared with nonpalmitoylated R7BP, palmitoylated R7BP greatly augments the ability of RGS7 to attenuate GPCR-mediated G protein–regulated inward rectifying potassium channel activation. Thus, by controlling plasma membrane nuclear–shuttling of R7BP–R7–Gβ5 complexes, reversible palmitoylation of R7BP provides a novel mechanism that regulates GPCR signaling and potentially transduces signals directly from the plasma membrane to the nucleus. PMID:15897264

  3. Tax1BP1 interacts with papillomavirus E2 and regulates E2-dependent transcription and stability.

    PubMed

    Wang, Xiaoyu; Naidu, Samisubbu R; Sverdrup, Francis; Androphy, Elliot J

    2009-03-01

    The papillomavirus E2 proteins regulate viral replication, gene transcription, and genome maintenance by interacting with other viral and host proteins. From a yeast two-hybrid screen, we identified the cellular protein Tax1BP1 as a novel binding partner of human papillomavirus type 18 (HPV18) E2. Tax1BP1 also interacts with the HPV16 and bovine papillomavirus type 1 (BPV1) E2 proteins, with the C-terminal region of Tax1BP1 interacting with the N-terminal transactivation domain of BPV1 E2. Tax1BP1 complexes with p300 and acts synergistically as a coactivator with p300 to enhance E2-dependent transcription. Using chromatin immunoprecipitation assays, we show that Tax1BP1 and E2 localize to the long control region on the BPV1 genome. Tax1BP1 was recently reported to bind ubiquitin and to function as an essential component of an A20 ubiquitin-editing complex. We demonstrate that Tax1BP1 plays a role in the regulation of the steady-state level of E2 by preventing its proteasomal degradation. These studies provide new insights into the regulation of E2 functions. PMID:19109394

  4. 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...

  5. 40 CFR 152.20 - Exemptions for pesticides adequately regulated by another Federal agency.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 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...

  6. 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:…

  7. 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 and adequate veterinary care. (a)...

  8. 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 Veterinarian and Adequate Veterinary Care §...

  9. 75 FR 69648 - Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... SAFETY BOARD Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers... TO THE SECRETARY OF ENERGY Safety Analysis Requirements for Defining Adequate Protection for the... safety analysis, or DSA, is to be prepared for every DOE nuclear facility. This DSA, once approved by...

  10. 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...

  11. 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...

  12. 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...

  13. 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

  14. Bovine hemoglobin as the sole source of dietary iron does not support adequate iron status in copper-adequate or copper-deficient rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This experiment was designed to determine whether hemoglobin as the sole source of dietary iron (Fe) could sustain normal Fe status in growing rats. Because adequate copper (Cu) status is required for efficient Fe absorption in the rat, we also determined the effects of Cu deficiency on Fe status of...

  15. A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination.

    PubMed

    Rocha, Pedro P; Raviram, Ramya; Fu, Yi; Kim, JungHyun; Luo, Vincent M; Aljoufi, Arafat; Swanzey, Emily; Pasquarella, Alessandra; Balestrini, Alessia; Miraldi, Emily R; Bonneau, Richard; Petrini, John; Schotta, Gunnar; Skok, Jane A

    2016-06-28

    During class switch recombination (CSR), B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH), altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs) in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR. PMID:27320916

  16. 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.

  17. 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...

  18. 53BP1 mediates the fusion of mammalian telomeres rendered dysfunctional by DNA-PKcs loss or inhibition.

    PubMed

    Rybanska-Spaeder, Ivana; Ghosh, Rajib; Franco, Sonia

    2014-01-01

    Telomere dysfunction promotes genomic instability and carcinogenesis via inappropriate end-to-end chromosomal rearrangements, or telomere fusions. Previous work indicates that the DNA Damage Response (DDR) factor 53BP1 promotes the fusion of telomeres rendered dysfunctional by loss of TRF2, but is dispensable for the fusion of telomeres lacking Pot1 or critically shortened (in telomerase-deficient mice). Here, we examine a role for 53BP1 at telomeres rendered dysfunctional by loss or catalytic inhibition of DNA-PKcs. Using mouse embryonic fibroblasts lacking 53BP1 and/or DNA-PKcs, we show that 53BP1 deficiency suppresses G1-generated telomere fusions that normally accumulate in DNA-PKcs-deficient fibroblasts with passage. Likewise, we find that 53BP1 promotes telomere fusions during the replicative phases of the cell cycle in cells treated with the specific DNA-PKcs inhibitor NU7026. However, telomere fusions are not fully abrogated in DNA-PKcs-inhibited 53BP1-deficient cells, but occur with a frequency approximately 10-fold lower than in control 53BP1-proficient cells. Treatment with PARP inhibitors or PARP1 depletion abrogates residual fusions, while Ligase IV depletion has no measurable effect, suggesting that PARP1-dependent alternative end-joining operates at low efficiency at 53BP1-deficient, DNA-PKcs-inhibited telomeres. Finally, we have also examined the requirement for DDR factors ATM, MDC1 or H2AX in this context. We find that ATM loss or inhibition has no measurable effect on the frequency of NU7026-induced fusions in wild-type MEFs. Moreover, analysis of MEFs lacking both ATM and 53BP1 indicates that ATM is also dispensable for telomere fusions via PARP-dependent end-joining. In contrast, loss of either MDC1 or H2AX abrogates telomere fusions in response to DNA-PKcs inhibition, suggesting that these factors operate upstream of both 53BP1-dependent and -independent telomere rejoining. Together, these experiments define a novel requirement for 53BP1 in

  19. 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. PMID:27462807

  20. Anti-BP180-type mucous membrane pemphigoid immunoglobulin G shows heterogeneity of internalization of BP180/collagen XVII into keratinocyte cytoplasm.

    PubMed

    Imanishi, Akiko; Imanishi, Hisayoshi; Hiroyasu, Sho; Ozawa, Toshiyuki; Koga, Hiroshi; Ishii, Norito; Kitajima, Yasuo; Hashimoto, Takashi; Tsuruta, Daisuke

    2016-06-01

    Anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is a rare autoimmune subepidermal blistering disease that targets the C terminus of BP180/collagen XVII. Currently, the pathomechanism of BP180-MMP is not well understood. We reported previously that immunoglobulin G (IgG) from patients with bullous pemphigoid (BP) can induce internalization of BP180 via a macropinocytic pathway, which depletes BP180 and weakens epidermal cell-matrix integrity. The purpose of the present study was to elucidate the pathomechanism of BP180-MMP. Immunohistochemistry of biopsy specimens from two patients with BP180-MMP revealed that one patient had BP180 internalization, but the other did not. In live-cell imaging using IgG from patients with BP180-MMP on several keratinocyte cell lines, IgG from only three out of the seven patients was associated with BP180 internalization into the cytoplasm. Our results suggest that IgG from patients with BP180-MMP shows heterogeneity of internalization of BP180. This variability in BP180 internalization in patients with BP or BP180-MMP may lead to differences in clinical presentation. PMID:26658728

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

    PubMed Central

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

    2015-01-01

    Separate mixed model analyses of variance (ANOVA) 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 = 1203). Multiple regressions examined whether accuracy in text consistency judgments uniquely accounted for variance in comprehension. Results suggest that there is considerable growth across the middle and high school years, particularly for adequate comprehenders in those text integration processes that maintain local coherence. Accuracy in text consistency judgments accounted for significant unique variance for passage-level, but not sentence-level comprehension, particularly for adequate comprehenders. PMID:26166946

  2. Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex

    PubMed Central

    Elbediwy, Ahmed; Zihni, Ceniz; Terry, Stephen J.; Clark, Peter

    2012-01-01

    Epithelial cell–cell adhesion and morphogenesis require dynamic control of actin-driven membrane remodeling. The Rho guanosine triphosphatase (GTPase) Cdc42 regulates sequential molecular processes during cell–cell junction formation; hence, mechanisms must exist that inactivate Cdc42 in a temporally and spatially controlled manner. In this paper, we identify SH3BP1, a GTPase-activating protein for Cdc42 and Rac, as a regulator of junction assembly and epithelial morphogenesis using a functional small interfering ribonucleic acid screen. Depletion of SH3BP1 resulted in loss of spatial control of Cdc42 activity, stalled membrane remodeling, and enhanced growth of filopodia. SH3BP1 formed a complex with JACOP/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein; both were required for normal Cdc42 signaling and junction formation. The filamentous actin–capping protein CapZ also associated with the SH3BP1 complex and was required for control of actin remodeling. Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics. PMID:22891260

  3. 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

  4. Possible enhancement of BP180 autoantibody production by herpes zoster.

    PubMed

    Kamiya, Koji; Aoyama, Yumi; Suzuki, Takahiro; Niwa, Haruo; Horio, Ai; Nishio, Eiichi; Tokura, Yoshiki

    2016-02-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies against type XVII collagen/BP180 (BP180). Although the mechanisms of autoantibody production remain to be elucidated, herpes virus infections have been identified as a possible triggering factor for pemphigus. We report a case of herpes zoster (HZ) having anti-BP180 serum antibodies. The patient developed sudden-onset, tense blisters and edematous erythema on the right anterior chest, shoulder and upper back. Histopathology showed remarkable degeneration of keratinocytes, acantholysis and blister formation with ballooning cells, indicating herpes virus infection. A polymerase chain reaction analysis of varicella zoster virus (VZV) was positive in crusts and effusions from the skin lesions, confirming the definitive diagnosis of HZ. Notably, we found that the patient had anti-BP180 serum antibodies in association with the occurrence of HZ. After successful treatment with valacyclovir hydrochloride for 7 days, the serum levels of anti-BP180 antibodies decreased in accordance with the improvement of skin lesions. These findings suggest that the production of anti-BP180 antibodies could be triggered by the reactivation of VZV. PMID:26212492

  5. CoCo trial: Color-coded blood pressure Control, a randomized controlled study

    PubMed Central

    Chmiel, Corinne; Senn, Oliver; Rosemann, Thomas; Del Prete, Valerio; Steurer-Stey, Claudia

    2014-01-01

    Background Inadequate blood pressure (BP) control is a frequent challenge in general practice. The objective of this study was to determine whether a color-coded BP booklet using a traffic light scheme (red, >180 mmHg systolic BP and/or >110 mmHg diastolic BP; yellow, >140–180 mmHg systolic BP or >90–110 mmHg diastolic BP; green, ≤140 mmHg systolic BP and ≤90 mmHg diastolic BP) improves BP control and adherence with home BP measurement. Methods In this two-group, randomized controlled trial, general practitioners recruited adult patients with a BP >140 mmHg systolic and/or >90 mmHg diastolic. Patients in the control group received a standard BP booklet and the intervention group used a color-coded booklet for daily home BP measurement. The main outcomes were changes in BP, BP control (treatment goal <140/90 mmHg), and adherence with home BP measurement after 6 months. Results One hundred and twenty-one of 137 included patients qualified for analysis. After 6 months, a significant decrease in systolic and diastolic BP was achieved in both groups, with no significant difference between the groups (16.1/7.9 mmHg in the intervention group versus 13.1/8.6 mmHg in the control group, P=0.3/0.7). BP control (treatment target <140/90 mmHg) was achieved significantly more often in the intervention group (43% versus 25%; P=0.037; number needed to treat of 5). Adherence with home BP measurement overall was high, with a trend in favor of the intervention group (98.6% versus 96.2%; P=0.1) Conclusion Color-coded BP self-monitoring significantly improved BP control (number needed to treat of 5, meaning that every fifth patient utilizing color-coded self-monitoring achieved better BP control after 6 months), but no significant between-group difference was observed in BP change. A markedly higher percentage of patients achieved BP values in the normal range. This simple, inexpensive approach of color-coded BP self-monitoring is user-friendly and applicable in primary care

  6. IGF2BP2 Alternative Variants Associated with Glutamic Acid Decarboxylase Antibodies Negative Diabetes in Malaysian Subjects

    PubMed Central

    Salem, Sameer D.; Saif-Ali, Riyadh; Ismail, Ikram S.; Al-Hamodi, Zaid; Poh, Rozaida; Muniandy, Sekaran

    2012-01-01

    Background The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects. Methods/Principal Findings IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively). Conclusions/Significance IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject. PMID:23029108

  7. 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

  8. Quantitative analysis of the interplay between hsc70 and its co-chaperone HspBP1

    PubMed Central

    Mahboubi, Hicham

    2015-01-01

    Background. Chaperones and their co-factors are components of a cellular network; they collaborate to maintain proteostasis under normal and harmful conditions. In particular, hsp70 family members and their co-chaperones are essential to repair damaged proteins. Co-chaperones are present in different subcellular compartments, where they modulate chaperone activities. Methods and Results. Our studies assessed the relationship between hsc70 and its co-factor HspBP1 in human cancer cells. HspBP1 promotes nucleotide exchange on hsc70, but has also chaperone-independent functions. We characterized the interplay between hsc70 and HspBP1 by quantitative confocal microscopy combined with automated image analyses and statistical evaluation. Stress and the recovery from insult changed significantly the subcellular distribution of hsc70, but had little effect on HspBP1. Single-cell measurements and regression analysis revealed that the links between the chaperone and its co-factor relied on (i) the physiological state of the cell and (ii) the subcellular compartment. As such, we identified a linear relationship and strong correlation between hsc70 and HspBP1 distribution in control and heat-shocked cells; this correlation changed in a compartment-specific fashion during the recovery from stress. Furthermore, we uncovered significant stress-induced changes in the colocalization between hsc70 and HspBP1 in the nucleus and cytoplasm. Discussion. Our quantitative approach defined novel properties of the co-chaperone HspBP1 as they relate to its interplay with hsc70. We propose that changes in cell physiology promote chaperone redistribution and thereby stimulate chaperone-independent functions of HspBP1. PMID:26713263

  9. 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

  10. 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.

  11. Methanococcus vannielii selenium-binding protein (SeBP): Chemical reactivity of recombinant SeBP produced in Escherichia coli

    PubMed Central

    Patteson, Kemberly G.; Trivedi, Neel; Stadtman, Thressa C.

    2005-01-01

    A selenium-binding protein (SeBP) from Methanococcus vannielii was recently identified, and its gene was isolated and overexpressed in Escherichia coli [Self, W. T., Pierce, R. & Stadtman, T. C. (2004) IUBMB Life 56, 501–507]. SeBP and recombinant SeBP (rSeBP) migrated as ≈42-kDa species on native gels and as ≈33-kDa species on SDS gels. rSeBP consists of identical 8.8-kDa subunits, each containing a single cysteine residue. rSeBP isolated in the absence of reducing agents contained oxidized cysteine (89%) and very little bound selenium (0.05 eq or less per subunit). Complete reduction of the oxidized cysteine residues in rSeBP with Tris(2-carboxyethyl)phosphine required addition of a denaturant, such as 1 M guanidine-hydrochloride. With selenite as the selenium source and the isolated reduced protein as sole reductant, binding of one selenium per tetramer under anaerobic conditions required four cysteine thiol groups, one on each subunit. In the corresponding reaction, with reduced glutathione (GSH), equimolar amounts of selenodiglutathione (GSSeSG) and glutathione disulfide are formed from selenite and 4 GSH. At GSH-to-selenite ratios >4:1, conversion of GSSeSG to a perselenide derivative, GSSe–, occurs. However, with the reduced rSeBP as sole electron donor in the reaction with selenite, further conversion of the R-SSeS-R product apparently did not occur. Prior alkylation of the cysteine thiol groups in reduced rSeBP prevented selenite reduction and selenium binding under comparable conditions. PMID:16103372

  12. 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....

  13. 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. PMID:15602692

  14. 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

  15. 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

  16. 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

  17. Bp'S Baku-Tbilisi-Ceyhan pipeline: the new corporate colonialism.

    PubMed

    Marriott, James; Muttitt, Greg

    2006-01-01

    An international campaign was waged questioning the benefits of BP's Baku-Tbilisi-Ceyhan pipeline in an effort to avoid a "zone of sacrifice" there. This article is an offshoot of that effort and explains the contemporary struggle over the pipeline project. The authors describe the project's background and evaluate the actual and potential impacts of the project in which they consider eight areas. They also assess BP's capacity to confront resistance to the pipeline. PMID:16867890

  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. PMID:26584654

  19. Is serum or sputum eosinophil cationic protein level adequate for diagnosis of mild asthma?

    PubMed

    Khakzad, Mohammad Reza; Mirsadraee, Majid; Sankian, Mojtaba; Varasteh, Abdolreza; Meshkat, Mojtaba

    2009-09-01

    Spirometry has been used as a common diagnostic test in asthma. Most of the patients with a mild asthma have a FEV1 within normal range. Hence, other diagnostic methods are usually used. The aim of this study was to evaluate whether eosinophil Cationic Protein (ECP) could be an accurate diagnostic marker of mild asthma. In this study diagnosis of asthma was made according to internationally accepted criteria. Asthma severity was evaluated according to frequency of symptoms and FEV1.Adequate sputum samples were obtained in 50 untreated subjects. A control group of 12 normal subjects that showed PC20 more than 8 mg/dl was also examined. Sputum was induced by inhalation of hypertonic saline. Inflammatory cells in sputum smears were assessed semi-quantitatively. ECP and IgE concentrations, eosinophil (EO) percentage and ECP/EO ratio in serum and sputum were also determined. The results revealed that Cough and dyspnea were the most frequent clinical findings. Dyspnea and wheezing were the symptoms that correlated with staging of asthma. FEV1 was within normal range (more than 80% of predicted) in 22 (44%) subjects.Asthmatic patients showed significantly higher numbers of blood eosinophils (4.5+/- 3.1% vs. 1.2+/-0.2%, P=0.009), and higher levels of serum ECP than control group (3.1+/- 2.6 % and 22.6+/- 15.8 ng/ml, respectively). Sputum ECP level in asthmatics was significantly higher than non- asthmatics (55.3+/-29.8ng/mL vs. 25.0+/-24.7ng/mL, P=0.045). Regression analysis showed no significant correlation between spirometric parameters and biomarkers, the only exception was significant correlation between FEF(25-75) and serum ECP (r= 0.28, P 0.041). Regarding clinical symptoms, wheezing was significantly correlated with elevation of most of biomarkers. Since, serum and sputum ECP levels are elevated in untreated asthmatics, the ECP level could be used for accurate diagnosis of mild form of asthma in which spirometry is unremarkable. PMID:20124607

  20. A method for determining adequate resistance form of complete cast crown preparations.

    PubMed

    Weed, R M; Baez, R J

    1984-09-01

    A diagram with various degrees of occlusal convergence, which takes into consideration the length and diameter of complete crown preparations, was designed as a guide to assist the dentist to obtain adequate resistance form. To test the validity of the diagram, five groups of complete cast crown stainless steel dies were prepared (3.5 mm long, occlusal convergence 10, 13, 16, 19, and 22 degrees). Gold copings were cast for each of the 50 preparations. Displacement force was applied to the casting perpendicularly to a simulated 30-degree cuspal incline until the casting was displaced. Castings were deformed at margins except for the 22-degree group. Castings from this group were displaced without deformation, and it was concluded that there was a lack of adequate resistance form as predicted by the diagram. The hypothesis that the diagram could be used to predict adequate or inadequate resistance form was confirmed by this study. PMID:6384470

  1. Comparison of four standards for determining adequate water intake of nursing home residents.

    PubMed

    Gaspar, Phyllis M

    2011-01-01

    Adequate hydration for nursing home residents is problematic. The purpose of this study was to compare four standards used to determine a recommended water intake among nursing home residents. Inconsistencies in the amount of water intake recommended based on the standards compared were identified. The standard based on height and weight provides the most individualized recommendation. An individualized recommendation would facilitate goal setting for the care plan of each older person and assist in the prevention of dehydration. It is essential that a cost-effective and clinically feasible approach to determine adequate water intake be determined for this population to prevent the adverse outcomes associated with dehydration. PMID:21469538

  2. 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

  3. Mechanisms Directing the Nuclear Localization of the CtBP Family Proteins

    PubMed Central

    Verger, Alexis; Quinlan, Kate G. R.; Crofts, Linda A.; Spanò, Stefania; Corda, Daniela; Kable, Eleanor P. W.; Braet, Filip; Crossley, Merlin

    2006-01-01

    The C-terminal binding protein (CtBP) family includes four proteins (CtBP1 [CtBP1-L], CtBP3/BARS [CtBP1-S], CtBP2, and RIBEYE) which are implicated both in transcriptional repression and in intracellular trafficking. However, the precise mechanisms by which different CtBP proteins are targeted to different subcellular regions remains unknown. Here, we report that the nuclear import of the various CtBP proteins and splice isoforms is differentially regulated. We show that CtBP2 contains a unique nuclear localization signal (NLS) located within its N-terminal region, which contributes to its nuclear accumulation. Using heterokaryon assays, we show that CtBP2 is capable of shuttling between the nucleus and cytoplasm of the cell. Moreover, CtBP2 can heterodimerize with CtBP1-L and CtBP1-S and direct them to the nucleus. This effect strongly depends on the CtBP2 NLS. PXDLS motif-containing transcription factors, such as BKLF, that bind CtBP proteins can also direct them to the nucleus. We also report the identification of a splice isoform of CtBP2, CtBP2-S, that lacks the N-terminal NLS and localizes to the cytoplasm. Finally, we show that mutation of the CtBP NADH binding site impairs the ability of the proteins to dimerize and to associate with BKLF. This reduces the nuclear accumulation of CtBP1. Our results suggest a model in which the nuclear localization of CtBP proteins is influenced by the CtBP2 NLS, by binding to PXDLS motif partner proteins, and through the effect of NADH on CtBP dimerization. PMID:16782877

  4. 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…

  5. 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

  6. 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…

  7. 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…

  8. 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...

  9. 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...

  10. 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...

  11. 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…

  12. 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...

  13. 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...

  14. 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…

  15. A Model for Touch Technique and Computation of Adequate Cane Length.

    ERIC Educational Resources Information Center

    Plain-Switzer, Karen

    1993-01-01

    This article presents a model for the motion of a long-cane executing the touch technique and presents formulas for the projected length of a cane adequate to protect an individual with blindness against wall-type and pole-type hazards. The paper concludes that the long-cane should reach from the floor to the user's armpit. (JDD)

  16. 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…

  17. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... animal health, behavior, and well-being is conveyed to the attending veterinarian; (4) Guidance to... 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...

  18. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... on problems of animal health, behavior, and well-being is conveyed to the attending veterinarian; (4... 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...

  19. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... on problems of animal health, behavior, and well-being is conveyed to the attending veterinarian; (4... 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...

  20. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... on problems of animal health, behavior, and well-being is conveyed to the attending veterinarian; (4... 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...

  1. 9 CFR 2.33 - Attending veterinarian and adequate veterinary care.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... animal health, behavior, and well-being is conveyed to the attending veterinarian; (4) Guidance to... 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...

  2. 9 CFR 2.40 - Attending veterinarian and adequate veterinary care (dealers and exhibitors).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... on problems of animal health, behavior, and well-being is conveyed to the attending veterinarian; (4... 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...

  3. Special or Not so Special: Special Education Background Experiences of Principals and Adequate Yearly Progress

    ERIC Educational Resources Information Center

    Wilcox, Jennifer E.

    2011-01-01

    This mixed-methods study researched the special education background experience of principals and the effect on students in the subgroup of Students with Disabilities in making Adequate Yearly Progress (AYP). In the state of Ohio, schools and districts are expected to make AYP as a whole and additionally make AYP for each subgroup (various…

  4. 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…

  5. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... with the State's requirements for availability of services, as set forth in § 438.206. (e) CMS' right... HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Quality Assessment and Performance... 42 Public Health 4 2010-10-01 2010-10-01 false Assurances of adequate capacity and services....

  6. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... requirements: (1) Offers an appropriate range of preventive, primary care, and specialty services that is adequate for the anticipated number of enrollees for the service area. (2) Maintains a network of providers... enrollment in its service area in accordance with the State's standards for access to care under this...

  7. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... requirements: (1) Offers an appropriate range of preventive, primary care, and specialty services that is adequate for the anticipated number of enrollees for the service area. (2) Maintains a network of providers... enrollment in its service area in accordance with the State's standards for access to care under this...

  8. 42 CFR 438.207 - Assurances of adequate capacity and services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... requirements: (1) Offers an appropriate range of preventive, primary care, and specialty services that is adequate for the anticipated number of enrollees for the service area. (2) Maintains a network of providers... enrollment in its service area in accordance with the State's standards for access to care under this...

  9. 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.

  10. Final 2004 Report on Adequate Yearly Progress in the Montgomery County Public Schools

    ERIC Educational Resources Information Center

    Stevenson, Jose W.

    2005-01-01

    The vast majority of Montgomery County public schools made sufficient progress on state testing and accountability standards in 2004 to comply with the adequate yearly progress (AYP) requirements under the "No Child Left Behind (NCLB) Act of 2001." Information released by the Maryland State Department of Education (MSDE) in October 2004 shows that…

  11. 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...

  12. 42 CFR 417.568 - Adequate financial records, statistical data, and cost finding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 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...

  13. Estimates of Adequate School Spending by State Based on National Average Service Levels.

    ERIC Educational Resources Information Center

    Miner, Jerry

    1983-01-01

    Proposes a method for estimating expenditures per student needed to provide educational adequacy in each state. Illustrates the method using U.S., Arkansas, New York, Texas, and Washington State data, covering instruction, special needs, operations and maintenance, administration, and other costs. Estimates ratios of "adequate" to actual spending…

  14. Leadership Style and Adequate Yearly Progress: A Correlational Study of Effective Principal Leadership

    ERIC Educational Resources Information Center

    Leapley-Portscheller, Claudia Iris

    2008-01-01

    Principals are responsible for leading efforts to reach increasingly higher levels of student academic proficiency in schools associated with adequate yearly progress (AYP) requirements. The purpose of this quantitative, correlational study was to identify the degree to which perceptions of principal transformational, transactional, and…

  15. 42 CFR 413.24 - Adequate cost data and cost finding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Adequate cost data and cost finding. 413.24 Section 413.24 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM PRINCIPLES OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY...

  16. Principals' Perceptions of Effective Strategies in Meeting Adequate Yearly Progress in Special Education

    ERIC Educational Resources Information Center

    Meyer, Jadie K.

    2012-01-01

    The purpose of this study was to examine the perceptions of principals who have met Adequate Yearly Progress (AYP) with the special education subgroup. This was a qualitative study, utilizing interviews to answer the research questions. The first three research questions analyzed the areas of assessment, building-level leadership, and curriculum…

  17. 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 ...

  18. 75 FR 74022 - Safety Analysis Requirements for Defining Adequate Protection for the Public and the Workers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... November 15, 2010 (75 FR 69648). The corrected text of the recommendation approved by the Board is below... or telephone number (202) 694-7000. Correction: In the Federal Register of November 15, 2010 (75 FR... SAFETY BOARD Safety Analysis Requirements for Defining Adequate Protection for the Public and the...

  19. Evaluating Rural Progress in Mathematics Achievement: Threats to the Validity of "Adequate Yearly Progress"

    ERIC Educational Resources Information Center

    Lee, Jaekyung

    2003-01-01

    This article examines major threats to the validity of Adequate Yearly Progress (AYP) in the context of rural schools. Although rural students and their schools made significant academic progress in the past on national and state assessments, the current goal of AYP turns out to be highly unrealistic for them unless states set far lower…

  20. 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 regulated by another Federal agency. 152.20 Section 152.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Exemptions for pesticides adequately regulated by another Federal agency. 152.20 Section 152.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Exemptions for pesticides adequately regulated by another Federal agency. 152.20 Section 152.20 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE REGISTRATION AND CLASSIFICATION...

  3. 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…

  4. 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.

  5. 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.

  6. Intervention for control of hypertension in Catalonia, Spain (INCOTECA Project): results of a multicentric, non-randomised, quasi-experimental controlled intervention study

    PubMed Central

    Rodriguez-Blanco, Teresa; Mengual-Martínez, Lucas; Rosell-Murphy, Magdalena; Prieto-De Lamo, Gemma; Martínez-Frutos, Fina; Mimoso-Moreno, Sonia; Bellerino-Serrano, Eva; Àlvarez-Lázaro, Alícia; Franzi-Sisó, Alícia; Martínez-Vindel, Juan Carlos; Alonso-Ortega, Mª Socorro; Olmedo-Muñoz, Imma; Bonet-Simó, Josep Mª

    2012-01-01

    Objective The purpose of this study was to assess the effectiveness of a quality improvement (QI) plan aimed at primary healthcare teams (PHCTs) to optimise hypertension control and to compare it with standard clinical care. Methods Design Multicentric, non-randomised, quasi-experimental controlled intervention study. Setting 5 PHCTs in the intervention and 13 in the standard care group in the province of Barcelona, Catalonia, Spain. Participants This is a population-based study in which all patients over 18 years of age with a diagnosis of hypertension before 1 January 2006 were included (n=9877 in the intervention group and n=21 704 in the control group). Intervention A QI plan that targeted primary care professionals. The plan included training sessions, implementation of recommended clinical practice guidelines for the management of hypertensive patients and audit and feedback to health professionals. Main outcome measure Prevalence of hypertensive patients with an adequate blood pressure (BP) control. Results The adjusted difference between intervention and standard care groups in the odds of BP control was 1.3 (95% CI 1.1 to 1.6, p=0.003). Results of the mixed model on repeated measures showed that, on average, an individual in the intervention group had an increase of 92% in the odds of BP control (OR 1.9, 95% CI 1.7 to 2.1). Conclusions The implementation of a QI plan can improve BP control. This strategy is potentially feasible for up-scaling within the existing PHCTs. Trial registration ClinicalTrials.gov MS: 1998275938244441. PMID:22514242

  7. Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats

    PubMed Central

    Lozić, Maja; Greenwood, Michael; Šarenac, Olivera; Martin, Andrew; Hindmarch, Charles; Tasić, Tatjana; Paton, Julian; Murphy, David; Japundžić-Žigon, Nina

    2014-01-01

    Background and Purpose The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis. Experimental Approach Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively. Key Results Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress. Conclusions and Implications OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease. PMID:24834854

  8. 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

  9. 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

  10. 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

  11. Endothelin-1 and the kidney – beyond BP

    PubMed Central

    Dhaun, Neeraj; Webb, David J; Kluth, David C

    2012-01-01

    Since its discovery over 20 years ago endothelin-1 (ET-1) has been implicated in a number of physiological and pathophysiological processes. Its role in the development and progression of chronic kidney disease (CKD) is well established and is an area of ongoing intense research. There are now available a number of ET receptor antagonists many of which have been used in trials with CKD patients and shown to reduce BP and proteinuria. However, ET-1 has a number of BP-independent effects. Importantly, and in relation to the kidney, ET-1 has clear roles to play in cell proliferation, podocyte dysfunction, inflammation and fibrosis, and arguably, these actions of ET-1 may be more significant in the progression of CKD than its prohypertensive actions. This review will focus on the potential role of ET-1 in renal disease with an emphasis on its BP-independent actions. PMID:22670597

  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. Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid.

    PubMed

    Bing, Liu; Xiping, Zhou; Li, Li; Jun, Peng; Yi-Xia, Wang; Min, Yang; Qing, Liu; Qiu-Ning, Sun; Hong-Zhong, Jin; Ya-Gang, Zuo

    2015-11-01

    Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum (r = -0.077, p > 0.05) or in blister fluid (r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid (r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of

  14. 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.

  15. 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

  16. 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

  17. Major Autonomic Neuroregulatory Pathways Underlying Short- and Long-Term Control of Cardiovascular Function.

    PubMed

    Salman, Ibrahim M

    2016-03-01

    Short-term and long-term blood pressure (BP) regulation and its maintenance at levels adequate to perfuse tissue organs involve an integrated action of multiple neural, cardiovascular, renal, endocrine and local tissue control systems. In the recent year, there has been a growing interest in the understanding of neural pathways key to BP control. For instance, through major advances in studies using both anesthetized and conscious animals, our knowledge of the essential neural mechanisms that subserve the baroreceptor, cardiopulmonary and chemoreceptor reflexes, and those evoked by the activation of stress pathways has dramatically increased. While the importance of these neural pathways in the maintenance of cardiovascular homeostasis is well established, the recognition of the central processing nuclei that integrate various afferent inputs to produce synchronous adjustments of autonomic outflows is still progressively expanding. Based on the literature provided thus far, the present review provides an overview in relation to the important neural determinants of BP control and later offers a concise description of major neuronal pathways that control autonomic outflows to the cardiovascular system in the short and long term. PMID:26838031

  18. A novel strategy to overcome resistance in stent placement at lesion site after adequate predilatation.

    PubMed

    Jain, D; Tolg, R; Katus, H A; Richardt, G

    2000-12-01

    Resistance was encountered in passing a 3 x 18 mm stent across a lesion in the proximal left anterior descending coronary artery. Successive changes in stent with repeated balloon dilatations did not succeed. Finally, a 9 mm stent was passed across the lesion and deployed at the site of maximal resistance. The 18 mm stent was then placed through this stent. A novel strategy to overcome resistance in the stent passage through the lesion after an adequate balloon predilatation is reported. PMID:11103034

  19. 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…

  20. 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. PMID:23761295

  1. 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

  2. Self-esteem, social support, and satisfaction differences in women with adequate and inadequate prenatal care.

    PubMed

    Higgins, P; Murray, M L; Williams, E M

    1994-03-01

    This descriptive, retrospective study examined levels of self-esteem, social support, and satisfaction with prenatal care in 193 low-risk postpartal women who obtained adequate and inadequate care. The participants were drawn from a regional medical center and university teaching hospital in New Mexico. A demographic questionnaire, the Coopersmith self-esteem inventory, the personal resource questionnaire part 2, and the prenatal care satisfaction inventory were used for data collection. Significant differences were found in the level of education, income, insurance, and ethnicity between women who received adequate prenatal care and those who received inadequate care. Women who were likely to seek either adequate or inadequate prenatal care were those whose total family income was $10,000 to $19,999 per year and high school graduates. Statistically significant differences were found in self-esteem, social support, and satisfaction between the two groups of women. Strategies to enhance self-esteem and social support have to be developed to reach women at risk for receiving inadequate prenatal care. PMID:8155221

  3. Pilot-scale treatability test plan for the 200-BP-5 operable unit

    SciTech Connect

    Not Available

    1994-08-01

    This document presents the treatability test plan for pilot-scale pump and treat testing at the 200-BP-5 Operable Unit. This treatability test plan has been prepared in response to an agreement between the U.S. Department of Energy (DOE), the U.S. Environmental Protection Agency (EPA), and the State of Washington Department of Ecology (Ecology), as documented in Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement, Ecology et al. 1989a) Change Control Form M-13-93-03 (Ecology et al. 1994) and a recent 200 NPL Agreement Change Control Form (Appendix A). The agreement also requires that, following completion of the activities described in this test plan, a 200-BP-5 Operable Unit Interim Remedial Measure (IRM) Proposed Plan be developed for use in preparing an Interim Action Record of Decision (ROD). The IRM Proposed Plan will be supported by the results of this treatability test plan, as well as by other 200-BP-5 Operable Unit activities (e.g., development of a qualitative risk assessment). Once issued, the Interim Action ROD will specify the interim action(s) for groundwater contamination at the 200-BP-5 Operable Unit. The treatability test approach is to conduct a pilot-scale pump and treat test for each of the two contaminant plumes associated with the 200-BP-5 Operable Unit. Primary contaminants of concern are {sup 99}Tc and {sup 60}Co for underwater affected by past discharges to the 216-BY Cribs, and {sup 90}Sr, {sup 239/240}Pu, and Cs for groundwater affected by past discharges to the 216-B-5 Reverse Well. The purpose of the pilot-scale treatability testing presented in this testplan is to provide the data basis for preparing an IRM Proposed Plan. To achieve this objective, treatability testing must: Assess the performance of groundwater pumping with respect to the ability to extract a significant amount of the primary contaminant mass present in the two contaminant plumes.

  4. 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.

  5. Bp44mT: an orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacy

    PubMed Central

    Yu, Y; Rahmanto, Y Suryo; Richardson, DR

    2012-01-01

    BACKGROUND AND PURPOSE Our previous studies demonstrated that a thiosemicarbazone iron chelator (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone; Dp44mT) possesses potent and selective anti-cancer activity but led to cardiotoxicity at non-optimal doses. In this study, we examined the in vivo anti-tumour efficacy and tolerability of a new-generation 2-benzoylpyridine thiosemicarbazone iron chelator (2-benzoylpyridine-4,4-dimethyl-3-thiosemicarbazone; Bp44mT) administered via the oral or i.v. routes. EXPERIMENTAL APPROACH BpT chelators were tested in vitro against human lung cancer cells (DMS-53) and in vivo in DMS-53 tumour xenografts in mice. The toxicity of Bp44mT in vivo and its effects on the expression of iron-regulated molecules involved in growth and cell cycle control were investigated. KEY RESULTS Administration of Bp44mT by either route resulted in marked dose-dependent inhibition of tumour growth. When administered at 50 mg·kg−1 via oral gavage three times per week for 23 days, the net xenograft growth was inhibited by 75%, compared with vehicle-treated mice. Toxicological examination showed reversible alterations including slight reduction of RBC count, with a decrease of liver and splenic iron levels, which confirmed iron chelation in vivo. Importantly, in contrast to Dp44mT, the chelator-treated mice did not show cardiac histological abnormalities. There was also no significant weight loss in mice, suggesting oral administration of Bp44mT was well tolerated. CONCLUSIONS AND IMPLICATIONS This is the first study to show that Bp44mT can be given orally with potent anti-tumour efficacy. Oral administration of a novel and effective chemotherapeutic agent provides the benefits of convenience for chronic dosing regimens. PMID:21658021

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

    PubMed

    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

    2015-08-01

    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

  7. 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

  8. Small Molecule, NSC95397, Inhibits the CtBP1-Protein Partner Interaction and CtBP1-Mediated Transcriptional Repression.

    PubMed

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

    2015-06-01

    Carboxyl-terminal binding protein (CtBP) is a transcriptional corepressor that suppresses multiple proapoptotic 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 also increases apoptosis independent of p53 in cell culture. Therefore, targeting CtBP with small molecules that disrupt its interaction with transcription factor partners may be an effective cancer therapy. To elicit its corepressing 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, lactase dehydrogenase. 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

  9. Evaluation of ELISA testing for BP180 and BP230 as a diagnostic modality for bullous pemphigoid: a clinical experience.

    PubMed

    Keller, Jesse J; Kittridge, Ashley L; Debanne, Sara M; Korman, Neil J

    2016-05-01

    Bullous pemphigoid (BP) is a common autoimmune blistering disorder of the elderly. Several diagnostic modalities are available, including clinical impression, histopathology, direct and indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) detection of pathogenic antibodies. In this study, we aim to examine the utility of the newest test, ELISA, in comparison to the constellation of other tests. We describe our clinical experience in which 170 patients diagnosed with bullous pemphigoid had multiple tests performed. BP180 alone showed a sensitivity of 54 % and specificity of 94 %. The positive predictive value (PPV) is 95 % while the negative predictive value (NPV) is 52 %. BP230 alone yielded a sensitivity of 48 % and specificity of 94 %. The PPV is 94 % and the NPV is 49 %. Using both tests in combination yielded a sensitivity of 66 % and specificity of 89 %. The PPV of at least one of two tests returning positive is 92 % while the NPV of dual negative tests is 58 %. Use of ELISAs for suspected cases of BP are an inadequate standalone test, and are only helpful in making the diagnosis should they return positive. However, they would appear to miss about one-third of cases. PMID:26895534

  10. 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

  11. 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

  12. 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

  13. Family Structure Types and Adequate Utilization of Antenatal Care in Kenya.

    PubMed

    Owili, Patrick Opiyo; Muga, Miriam Adoyo; Chou, Yiing-Jenq; Hsu, Yi-Hsin Elsa; Huang, Nicole; Chien, Li-Yin

    2016-01-01

    Features of the health care delivery system may not be the only expounding factors of adequate utilization of antenatal care among women. Other social factors such as the family structure and its environment contribute toward pregnant women's utilization of antenatal care. An understanding of how women in different family structure types and social groups use basic maternal health services is important toward developing and implementing maternal health care policy in the post-Millennium Development Goal era, especially in the sub-Saharan Africa where maternal mortality still remains high. PMID:27214674

  14. Working group on the “adequate minimum” V=volcanic observatory

    USGS Publications Warehouse

    Tilling, R.I.

    1982-01-01

    A working group consisting of R. I. Tilling (United States, Chairman), M. Espendola (Mexico), E. Malavassi (Costa Rica), L. Villari (Italy), and J.P Viode (France) met on the island of Guadeloupe on February 20, 1981, to discuss informally the requirements for a "Minimum" volcano observatory, one which would have the essential monitoring equipment and staff to provide reliable information on the state of an active volcno. Given the premise that any monitoring of a volcano is better than none at all, the owrking group then proceeded to consider the concept of an "adequate minimum" observatory. 

  15. Prevalence of Optimal Treatment Regimens in Patients with Apparent Treatment Resistant Hypertension Based on Office BP in a Community-Based Practice Network

    PubMed Central

    Egan, Brent M.; Zhao, Yumin; Li, Jiexiang; Brzezinski, W. Adam; Todoran, Thomas M.; Brook, Robert D.; Calhoun, David A.

    2013-01-01

    Hypertensive patients with clinic blood pressure (BP) uncontrolled on ≥3 antihypertensive medications, i.e., apparent treatment resistant hypertension (aTRH) comprise ~28%–30% of all uncontrolled patients in the U.S. However, the proportion receiving these medications in optimal doses is unknown; aTRH is used, since treatment adherence, BP measurement artifacts, and optimal therapy were not available in electronic record data from our >200 community-based clinics Outpatient QUuality Improvement Network (OQUIN). This study sought to define the proportion of uncontrolled hypertensives with aTRH on optimal regimens and clinical factors associated with optimal therapy. During 2007–2010, 468,877 hypertensive patients met inclusion criteria. BP <140/<90 defined control. Multivariable logistic regression was used to assess variables independently associated with ‘optimal therapy’ (prescription of diuretic and ≥2 other BP medications at ≥50% of maximum recommended hypertension doses). Among 468,877 hypertensives, 147,635 (31.5%) were uncontrolled; among uncontrolled hypertensives, 44,684 were prescribed ≥3 BP medications (30.3%) of which 22,189 (15.0%) were prescribed ‘optimal’ therapy. Clinical factors independently associated with optimal BP therapy included black race (OR 1.40 [95% CI 1.32–1.49]), chronic kidney disease (1.31 [1.25–1.38]) diabetes (1.30 [1.24–1.37]), and coronary heart disease risk equivalent status (1.29 [1.14–1.46]). Clinicians more often prescribe optimal therapy for aTRH when cardiovascular risk is greater and treatment goals lower. Approximately one in seven of all uncontrolled hypertensives and one in two with uncontrolled aTRH are prescribed ≥3 BP medications in optimal regimens. Prescribing more optimal pharmacotherapy, for uncontrolled hypertensives including aTRH, confirmed with out-of-office BP, could improve hypertension control. PMID:23918752

  16. Gate tunable WSe2-BP van der Waals heterojunction devices

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Zhang, Ting Ting; Zhang, Jing; Xiang, Jianyong; Yu, Hua; Wu, Shuang; Lu, Xiaobo; Wang, Guole; Wen, Fusheng; Liu, Zhongyuan; Yang, Rong; Shi, Dongxia; Zhang, Guangyu

    2016-02-01

    Due to the weak screening effect, the concentration and type of charge carriers in 2D semiconductor heterostructures can be effectively tuned by electrostatic gating, enabling us to realize different types of heterojunctions in a single device. Such `type tunable' properties are useful for designing novel electrical or optoelectrical devices. Here, we demonstrate a `type tunable' heterojunction device construct with two pieces of ambipolar 2D semiconductors: WSe2 and black phosphorus (BP). This heterojunction could be tuned to either the p-p junction or n-n junction by gate modulation. The p-p junction shows a large current rectification ratio while the n-n junction shows a negligible current rectification ratio, indicating a large valence band offset and a small conduction band offset at the WSe2/BP interface. In the optoelectrical measurements, we found the amplitude and even the polarity of photocurrent could be modulated by electrostatic gating. Our study could further enhance the understanding of designing devices based on these `type tunable' van der Waals heterojunctions. Moreover, the properties of the WSe2/BP interface were also experimentally identified through the electrical and optoelectrical measurements in our study.Due to the weak screening effect, the concentration and type of charge carriers in 2D semiconductor heterostructures can be effectively tuned by electrostatic gating, enabling us to realize different types of heterojunctions in a single device. Such `type tunable' properties are useful for designing novel electrical or optoelectrical devices. Here, we demonstrate a `type tunable' heterojunction device construct with two pieces of ambipolar 2D semiconductors: WSe2 and black phosphorus (BP). This heterojunction could be tuned to either the p-p junction or n-n junction by gate modulation. The p-p junction shows a large current rectification ratio while the n-n junction shows a negligible current rectification ratio, indicating a large valence

  17. Organizing person-centred care in paediatric diabetes: multidisciplinary teams, long-term relationships and adequate documentation

    PubMed Central

    2014-01-01

    Background Type 1 diabetes is one of the most frequent long-term endocrine childhood disorders and the Swedish National Diabetes Register for children states that adolescents (12–18 years) constitute the most vulnerable patient group in terms of metabolic control. The aim of this study was to examine how a multidisciplinary team functions when caring for adolescents with type 1 diabetes. Methods Qualitative interviews were performed with 17 health professionals at a Paediatric Diabetes Care Unit in a Swedish university hospital. The interviews were analysed to gain insight into a multidisciplinary care team’s experiences of various organizational processes and circumstances related to the provision of person-centred paediatric diabetes care. Results Building long-term relationships with adolescents, the establishment of a multidisciplinary care team and ensuring adequate documentation are vital for the delivery of person-centred care (PCC). Furthermore, a PCC process and/or practice requires more than the mere expression of person-centred values. The contribution of this study is that it highlights the necessity of facilitating and safeguarding the organization of PCC, for which three processes are central: 1. Facilitating long-term relationships with adolescents and their families; 2. Facilitating multi-professional teamwork; and 3. Ensuring adequate documentation. Conclusion Three processes emerged as important for the functioning of the multidisciplinary team when caring for adolescents with type 1 diabetes: building a long-term relationship, integrating knowledge by means of multidisciplinary team work and ensuring adequate documentation. This study demonstrates the importance of clearly defining and making use of the specific role of each team member in the paediatric diabetes care unit (PDCU). Team members should receive training in PCC and a PCC approach should form the foundation of all diabetes care. Every adolescent suffering from type 1 diabetes

  18. Temperature Control. Honeywell Planning Guide.

    ERIC Educational Resources Information Center

    Honeywell, Inc., Minneapolis, Minn.

    Presents planning considerations in selecting proper temperature control systems. Various aspects are discussed including--(1) adequate environmental control, (2) adequate control area, (3) control system design, (4) operators rate their systems, (5) type of control components, (6) basic control system, (7) automatic control systems, and (8)…

  19. 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.

  20. Adequate Systemic Perfusion Maintained by a CentriMag during Acute Heart Failure

    PubMed Central

    Favaloro, Roberto R.; Bertolotti, Alejandro; Diez, Mirta; Favaloro, Liliana; Gomez, Carmen; Peradejordi, Margarita; Trentadue, Julio; Hellman, Lorena; Arzani, Yanina; Otero, Pilar Varela

    2008-01-01

    Mechanical circulatory support during severe acute heart failure presents options for myocardial recovery or cardiac replacement. Short-term circulatory support with the newest generation of magnetically levitated centrifugal-flow pumps affords several potential advantages. Herein, we present our experience with such a pump—the CentriMag® (Levitronix LLC; Waltham, Mass) centrifugal-flow ventricular assist device—in 4 critically ill patients who were in cardiogenic shock. From November 2007 through March 2008, 3 patients were supported after cardiac surgery, and 1 after chronic heart failure worsened. Two patients were bridged to heart transplantation, and 2 died during support. Perfusion during support was evaluated in terms of serum lactic acid levels and oxygenation values. In all of the patients, the CentriMag's pump flow was adequate, and continuous mechanical ventilation support was provided. Lactic acid levels substantially improved with CentriMag support and were maintained at near-normal levels throughout. At the same time, arterial pH, PO2, and carbon dioxide levels remained within acceptable ranges. No thromboembolic events or mechanical failures occurred. Our experience indicates that short-term use of the CentriMag ventricular assist device during acute heart failure can restore and adequately support circulation until recovery or until the application of definitive therapy. PMID:18941648

  1. 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.

  2. Spectropolarimetry of the classical T Tauri star BP Tauri

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Johns-Krull, Christopher

    2012-05-01

    We implement a least-squares deconvolution (LSD) code to study magnetic fields on cool stars. We first apply our code to high resolution (R ~ 60,000) optical echelle spectra of several solar-like stars as tests of the code and to measure the mean longitudinal magnetic field on the surface of these stars. Null results or weak fields are detected on the solar-like stars as is expected, demonstrating the functionality of the LSD code. We then apply our LSD code to 6 nights of data on the Classical T Tauri Star BP Tau. A maximum field of 330 +/- 80 G is detected from the photospheric lines on BP Tau. Measurements of several emission lines (He I 5876 A˚, Ca II 8498 A˚ and 8542 A˚) show the presence of strong magnetic fields in the line formation regions, which are believed to be the base of the accretion footpoints.

  3. 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.

  4. 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

  5. [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

  6. 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.

  7. 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).

  8. Identification of novel mutations in CD2BP1 gene in clinically proven rheumatoid arthritis patients of south India.

    PubMed

    Kumar, Bhattaram Siddhartha; Kumar, Pasupuleti Santhosh; Sowgandhi, Nannepaga; Prajwal, Bhattaram Manoj; Mohan, Alladi; Sarma, Kadainti Venkata Subbaraya; Sarma, Potukuchi Venkata Gurunadha Krishna

    2016-08-01

    Pyogenic Arthritis, Pyoderma gangrenosum, and Acne (PAPA syndrome) is a rare autosomal dominant, auto-inflammatory disease that affects joints and skin. The disease results due to mutations in the cluster of differentiation 2 binding protein 1 (CD2BP1) gene on chromosome 15q24.3. Rheumatoid arthritis (RA) is a common, genetically complex disease that affects the joints with occasional skin manifestations. Studies related to the pathophysiology of inflammation in these two disorders show a certain degree of overlap at genetic level. The present study was done to confirm the existence of such a genetic overlap between PAPA syndrome and RA in south Indian population. In the present study 100 patients who were clinically diagnosed rheumatoid arthritis and 100 apparently healthy controls were chosen and the 15 exons of CD2BP1 gene were PCR-amplified and sequenced. The sequence analysis showed that in exon 3 thirty eight patients revealed presence of novel heterozygous missense mutations p.Glu51Asp, p.Leu57Arg and p.Ala64Thr. In exons 6, 10 and 14 eight patients showed 44 novel missense mutations and two patients showed novel frame shift mutations p.(Met123_Leu416delinsThr) and p.(Thr337Profs*52) leading to truncated protein formation. Such mutations were not seen in controls. Further, the in silico analysis revealed the mutant CD2BP1 structure showed deletion of Cdc15 and SH3 domains when superimposed with the wild type CD2BP1 structure with variable RMSD values. Therefore, these structural variations in CD2BP1 gene due to the mutations could be one of the strongest reasons to demonstrate the involvement of these gene variations in the patients with rheumatoid arthritis. PMID:27184502

  9. Gate tunable WSe2-BP van der Waals heterojunction devices.

    PubMed

    Chen, Peng; Zhang, Ting Ting; zhang, Jing; Xiang, Jianyong; Yu, Hua; Wu, Shuang; Lu, Xiaobo; Wang, Guole; Wen, Fusheng; Liu, Zhongyuan; Yang, Rong; Shi, Dongxia; Zhang, Guangyu

    2016-02-14

    Due to the weak screening effect, the concentration and type of charge carriers in 2D semiconductor heterostructures can be effectively tuned by electrostatic gating, enabling us to realize different types of heterojunctions in a single device. Such 'type tunable' properties are useful for designing novel electrical or optoelectrical devices. Here, we demonstrate a 'type tunable' heterojunction device construct with two pieces of ambipolar 2D semiconductors: WSe2 and black phosphorus (BP). This heterojunction could be tuned to either the p-p junction or n-n junction by gate modulation. The p-p junction shows a large current rectification ratio while the n-n junction shows a negligible current rectification ratio, indicating a large valence band offset and a small conduction band offset at the WSe2/BP interface. In the optoelectrical measurements, we found the amplitude and even the polarity of photocurrent could be modulated by electrostatic gating. Our study could further enhance the understanding of designing devices based on these 'type tunable' van der Waals heterojunctions. Moreover, the properties of the WSe2/BP interface were also experimentally identified through the electrical and optoelectrical measurements in our study. PMID:26810387

  10. 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).

  11. An investigation into the association between HLA-G 14 bp insertion/deletion polymorphism and multiple sclerosis susceptibility.

    PubMed

    Mohammadi, Nabiallah; Adib, Minoo; Alsahebfosoul, Fereshteh; Kazemi, Mohammad; Etemadifar, Masoud

    2016-01-15

    Human Leukocyte Antigen G (HLA-G) gene polymorphism and expression rate have recently been suggested to have a potential role in susceptibility to Multiple Sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. The aim of this study was to investigate the association of the frequency of HLA-G gene 14 bp insertion/deletion polymorphism and its plasma level with MS susceptibility. In this study, the HLA-G gene from 212 patients and 210 healthy individuals was amplified using real time PCR and screened for the 14 bp insertion/deletion polymorphism. In addition, HLA-G plasma levels of the patients were measured and compared to normal controls by ELISA method. Our results revealed that 14 bp insertion in HLA-G could result in lower plasma HLA-G level of the subjects, regardless of their health status and vice versa. Additionally, significant correlation of HLA-G genotype and its plasma level with MS susceptibility was observed. In conclusion, not only HLA-G 14 bp insertion/deletion polymorphism could be associated with expression rate of the HLA-G gene and its plasma level, but also could be considered as a risk factor for susceptibility to MS in our study population. PMID:26711580

  12. Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn's disease.

    PubMed

    Zidi, Inès; Ben Yahia, Hamza; Bortolotti, Daria; Mouelhi, Leila; Laaribi, Ahmed Baligh; Ayadi, Shema; Zidi, Nour; Houissa, Fatma; Debbech, Radhouane; Boudabous, Abdellatif; Najjar, Taoufik; Di Luca, Dario; Rizzo, Roberta

    2015-06-01

    The aim of this study was to evaluate the association between the HLA-G 14-bp deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in patients with Crohn's disease (CD). We analyzed also the sHLA-G molecules by ELISA and western blot in plasma samples. Among unselected patients, the 14-bp Del/Ins polymorphism was not significantly associated with increased CD risk neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a significant association was reported between the 14-bp Del/Ins polymorphism and CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset CD patients. A significant association was reported concerning the genotype Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77). We observed also a significant increase in sHLA-G measured by ELISA in CD patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of subjects present dimers of HLA-G. The presence of dimers seems to be related to the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated with an increased risk of CD particularly in young-onset CD patients and controls sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages. The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8 of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G as a prognostic marker for progressive disease. PMID:25577194

  13. The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells.

    PubMed

    Motomura, Yasutaka; Kitamura, Hiroshi; Hijikata, Atsushi; Matsunaga, Yuko; Matsumoto, Koichiro; Inoue, Hiromasa; Atarashi, Koji; Hori, Shohei; Watarai, Hiroshi; Zhu, Jinfang; Taniguchi, Masaru; Kubo, Masato

    2011-05-01

    The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (T(H)2) cells but also by T(H)1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic T(H)1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3(-/-); called 'E4bp4(-/-)' here) T(H)1 cells, regulatory T cells (T(reg) cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional T(H)1 cells. E4bp4(-/-) T(H)2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in T(H)1 cells and IL-10 in T(H)1 cells, T(H)2 cells, T(reg) cells and NKT cells. PMID:21460847

  14. 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

  15. 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..

  16. Do measures commonly used in body image research perform adequately with African American college women?

    PubMed

    Kashubeck-West, Susan; Coker, Angela D; Awad, Germine H; Stinson, Rebecca D; Bledman, Rashanta; Mintz, Laurie

    2013-07-01

    This study examines reliability and validity estimates for 3 widely used measures in body image research in a sample of African American college women (N = 278). Internal consistency estimates were adequate (α coefficients above .70) for all measures, and evidence of convergent and discriminant validity was found. Confirmatory factor analyses failed to replicate the hypothesized factor structures of these measures. Exploratory factor analyses indicated that 4 factors found for the Sociocultural Attitudes Toward Appearance Questionnaire were similar to the hypothesized subscales, with fewer items. The factors found for the Multidimensional Body-Self Relations Questionnaire-Appearance Scales and the Body Dissatisfaction subscale of the Eating Disorders Inventory-3 were not similar to the subscales developed by the scale authors. Validity and reliability evidence is discussed for the new factors. PMID:23731233

  17. 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.

  18. 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

  19. 41 CFR 102-75.150 - What happens when GSA determines that the report of excess is adequate?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... determines that the report of excess is adequate? 102-75.150 Section 102-75.150 Public Contracts and Property... PROPERTY 75-REAL PROPERTY DISPOSAL Utilization of Excess Real Property Examination for Acceptability § 102-75.150 What happens when GSA determines that the report of excess is adequate? When GSA...

  20. 41 CFR 102-75.150 - What happens when GSA determines that the report of excess is adequate?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... determines that the report of excess is adequate? 102-75.150 Section 102-75.150 Public Contracts and Property... PROPERTY 75-REAL PROPERTY DISPOSAL Utilization of Excess Real Property Examination for Acceptability § 102-75.150 What happens when GSA determines that the report of excess is adequate? When GSA...

  1. 41 CFR 102-75.150 - What happens when GSA determines that the report of excess is adequate?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... determines that the report of excess is adequate? 102-75.150 Section 102-75.150 Public Contracts and Property... PROPERTY 75-REAL PROPERTY DISPOSAL Utilization of Excess Real Property Examination for Acceptability § 102-75.150 What happens when GSA determines that the report of excess is adequate? When GSA...

  2. 41 CFR 102-75.150 - What happens when GSA determines that the report of excess is adequate?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... determines that the report of excess is adequate? 102-75.150 Section 102-75.150 Public Contracts and Property... PROPERTY 75-REAL PROPERTY DISPOSAL Utilization of Excess Real Property Examination for Acceptability § 102-75.150 What happens when GSA determines that the report of excess is adequate? When GSA...

  3. 41 CFR 102-75.150 - What happens when GSA determines that the report of excess is adequate?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... determines that the report of excess is adequate? 102-75.150 Section 102-75.150 Public Contracts and Property... PROPERTY 75-REAL PROPERTY DISPOSAL Utilization of Excess Real Property Examination for Acceptability § 102-75.150 What happens when GSA determines that the report of excess is adequate? When GSA...

  4. 21 CFR 1.284 - What are the other consequences of failing to submit adequate prior notice or otherwise failing...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... submit adequate prior notice or otherwise failing to comply with this subpart? 1.284 Section 1.284 Food... failing to submit adequate prior notice or otherwise failing to comply with this subpart? (a) The importing or offering for import into the United States of an article of food in violation of...

  5. 21 CFR 1.284 - What are the other consequences of failing to submit adequate prior notice or otherwise failing...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... submit adequate prior notice or otherwise failing to comply with this subpart? 1.284 Section 1.284 Food... failing to submit adequate prior notice or otherwise failing to comply with this subpart? (a) The importing or offering for import into the United States of an article of food in violation of...

  6. 21 CFR 1.284 - What are the other consequences of failing to submit adequate prior notice or otherwise failing...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... submit adequate prior notice or otherwise failing to comply with this subpart? 1.284 Section 1.284 Food... failing to submit adequate prior notice or otherwise failing to comply with this subpart? (a) The importing or offering for import into the United States of an article of food in violation of...

  7. 21 CFR 1.284 - What are the other consequences of failing to submit adequate prior notice or otherwise failing...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... submit adequate prior notice or otherwise failing to comply with this subpart? 1.284 Section 1.284 Food... failing to submit adequate prior notice or otherwise failing to comply with this subpart? (a) The importing or offering for import into the United States of an article of food in violation of...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  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. RanBP2 Modulates Cox11 and Hexokinase I Activities and Haploinsufficiency of RanBP2 Causes Deficits in Glucose Metabolism

    PubMed Central

    Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A

    2006-01-01

    The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2−/− are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2+/− mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies. PMID:17069463

  17. 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}.

  18. Estimating smoothness term for BP stereo matching with sparse disparities

    NASA Astrophysics Data System (ADS)

    He, Junxue; Li, Zhanming

    2011-06-01

    The belief propagation stereo matching algorithm has high computational cost and varied parameters. To address these problems and perform stereo matching in practical applications, we implement BP algorithm on cuda and propose an approach to estimate parameters of smoothness term in the energy function automatically. We use Harris corner detector and Pyramidal KLT feature tracker algorithm to extract a sparse disparity map. The rate of increase in the discontinuity cost can be compute out approximately. Experiments demonstrate that our approach is feasible and the approximate parameters of discontinuity cost can be computed out quickly.

  19. 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

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

    PubMed Central

    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

  1. 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.

  2. The rat adequately reflects human responses to exercise in blood biochemical profile: a comparative study.

    PubMed

    Goutianos, Georgios; Tzioura, Aikaterini; Kyparos, Antonios; Paschalis, Vassilis; Margaritelis, Nikos V; Veskoukis, Aristidis S; Zafeiridis, Andreas; Dipla, Konstantina; Nikolaidis, Michalis G; Vrabas, Ioannis S

    2015-02-01

    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

  3. 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.

  4. [Rhythmic nuclear growth of adequately stimulated ganglia cells of acoustic nuclei (rat)].

    PubMed

    Köpf-Maier, P; Wüstenfeld, E

    1975-01-01

    Ganglia cells of the dorsal and ventral cochlear nuclei of white rats were irritated adequately for different periods or left untreated, respectively, and investigated karyometrically. The frequency distribution curves of the nuclear volumes were separated by means of an electronic curve resolver into the component curves, i.e. into groups of nuclei obeying exactly a Gaussian normal distribution and thus representing biologically uniform populations. The analysis of the mean values of the component curves led to the following results: 1. The mean values of the component curves can be arranged in 2 series having the pattern V1, V1 square root 2, V2, V2 square root 2, V4, V4 square root 2...2. The series V1, V1 square root 2, V2, V2 square root 2...is based on a geometrical series of the general formula an = k-qn. 3. It follows from these results that the nuclear volumes grow rhythmically by a factor of square root 2 and, consequently, that there is a periodical doubling in in the growth of the surface. PMID:1200386

  5. A test of the cerebellar hypothesis of dyslexia in adequate and inadequate responders to reading intervention

    PubMed Central

    Barth, Amy E.; Denton, Carolyn A.; Stuebing, Karla K.; Fletcher, Jack M.; Cirino, Paul T.; Francis, David J.; Vaughn, Sharon

    2013-01-01

    The cerebellar hypothesis of dyslexia posits that cerebellar deficits are associated with reading disabilities and may explain why some individuals with reading disabilities fail to respond to reading interventions. We tested these hypotheses in a sample of children who participated in a grade 1 reading intervention study (n = 174) and a group of typically achieving children (n = 62). At posttest, children were classified as adequately responding to the intervention (n = 82), inadequately responding with decoding and fluency deficits (n = 36), or inadequately responding with only fluency deficits (n = 56). Based on the Bead Threading and Postural Stability subtests from the Dyslexia Screening Test-Junior, we found little evidence that assessments of cerebellar functions were associated with academic performance or responder status. In addition, we did not find evidence supporting the hypothesis that cerebellar deficits are more prominent for poor readers with “specific” reading disabilities (i.e., with discrepancies relative to IQ) than for poor readers with reading scores consistent with IQ. In contrast, measures of phonological awareness, rapid naming, and vocabulary were strongly associated with responder status and academic outcomes. These results add to accumulating evidence that fails to associate cerebellar functions with reading difficulties. PMID:20298639

  6. 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

  7. A negative cranial computed tomographic scan is not adequate to support a diagnosis of pseudotumor cerebri.

    PubMed

    Said, Rana R; Rosman, N Paul

    2004-08-01

    A 10-year-old boy with daily headache for 1 month and intermittent diplopia for 1 week was found to have a unilateral partial abducens palsy and bilateral papilledema; otherwise, his neurologic examination showed no abnormalities. A cranial computed tomographic (CT) scan was normal. Lumbar puncture disclosed a markedly elevated opening pressure of > 550 mm of cerebrospinal fluid with normal cerebrospinal fluid. Medical therapy with acetazolamide for presumed pseudotumor cerebri was begun. Magnetic resonance imaging (MRI) of the brain, done several days later because of continuing symptoms, unexpectedly showed multiple hyperintensities of cerebral white matter on T2-weighted and fluid-attenuated inversion recovery images. Despite high-dose intravenous methylprednisolone for possible demyelinating disease, he failed to improve. A left temporal brain biopsy followed and disclosed an anaplastic oligodendroglioma. In a patient with features indicating pseudotumor cerebri, a negative cranial CT scan is not adequate to rule out underlying pathology; thus, MRI of the brain should probably always be performed. A revised definition of pseudotumor cerebri could better include "normal MRI of the brain" rather than "normal neuroimaging." PMID:15605471

  8. 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.

  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. [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

  11. The menopause, hormone replacement therapy and informed consent: are women in an underresourced country adequately aware?

    PubMed

    Maharaj, N R; Gangaram, R; Moodley, J

    2007-04-01

    Recent evidence on the long-term effects of HRT have resulted in increased emphasis being placed on individualised counselling, patient choice and informed consent when managing the menopause. We assessed whether women in an underresourced country have adequate knowledge of the menopause/HRT to engage in patient - provider discussions and provide full informed consent for HRT. Specific 'knowledge scores' for the menopause and HRT were developed and utilised in structured questionnaires to determine the existing levels of knowledge in 150 women from different racial, educational and occupational backgrounds. Some 92% were aware of the menopause and 54% were aware of HRT. Specific knowledge about the menopause and HRT overall was low (39% and 38%, respectively). There was a significant association between higher education levels, race and occupational status on the knowledge of the menopause but not of HRT. Television, radio and pamphlets were the preferred sources to gain further information. There is a need to create awareness and provide further education to women in underresourced countries about the menopause and HRT to empower them to make informed choices about their health during this period. PMID:17464817

  12. 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.

  13. [Adequate attention is required to the diagnosis and treatment of mild-symptom erectile dysfunction].

    PubMed

    Deng, Chun-hua; Zhang, Ya-dong; Chen, Xin

    2015-01-01

    Mild-symptom erectile dysfunction (MSED) is commonly seen in clinical practice, but receives inadequate attention from both the patients and clinicians. Increasing researches have indicated that MSED is associated with not only unhealthy living habits and psychological factors but also the early progression of endothelial, metabolic and endocrine diseases. The diagnosis and treatment of MSED should be based on the relevant guidelines, with consideration of both its specific and common features. The therapeutic principle is a combination of integrated and individual solutions aimed at the causes of the disease. Drug intervention should be initiated if psychological therapy fails. Negligence of MSED may affect the quality of life of the patients and their partners, and what's more, might delay the management of some other severe underlying diseases. Adequate attention to the early diagnosis and treatment for MSED is of great significance for a deeper insight into the etiology of ED, the prevention of potential cardiovascular and metabolic diseases, and the improvement of the overall health of males. PMID:25707132

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

    NASA Technical Reports Server (NTRS)

    Juarez, Alfredo; Harper, Susana A.

    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.

  15. 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

  16. 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

  17. Is reimbursement for childhood immunizations adequate? evidence from two rural areas in colorado.

    PubMed Central

    Glazner, J. E.; Steiner, J. F.; Haas, K. J.; Renfrew, B.; Deutchman, M.; Berman, S.

    2001-01-01

    OBJECTIVE: To assess adequacy of reimbursement for childhood vaccinations in two rural regions in Colorado, the authors measured medical practice costs of providing childhood vaccinations and compared them with reimbursement. METHODS: A "time-motion" method was used to measure labor costs of providing vaccinations in 13 private and public practices. Practices reported non-labor costs. The authors determined reimbursement by record review. RESULTS: The average vaccine delivery cost per dose (excluding vaccine cost) ranged from $4.69 for community health centers to $5.60 for private practices. Average reimbursement exceeded average delivery costs for all vaccines and contributed to overhead in private practices. Average reimbursement was less than total cost (vaccine-delivery costs + overhead) in private practices for most vaccines in one region with significant managed care penetration. Reimbursement to public providers was less than the average vaccine delivery costs. CONCLUSIONS: Current reimbursement may not be adequate to induce private practices to provide childhood vaccinations, particularly in areas with substantial managed care penetration. PMID:12034911

  18. Adequate Vitamin D3 Supplementation During Pregnancy: Decreasing the Prevalence of Asthma and Food Allergies

    PubMed Central

    Finkel, Jonathan; Cira, Courtney; Mazzella, Leanne; Bartyzel, Jim; Ramanna, Annisce; Strimel, Kayla; Waturuocha, Amara; Musser, Nathan; Burress, James; Brammer, Sarah; Wetzel, Robert; Horzempa, Joseph

    2016-01-01

    Vitamin D is a secosterol that is naturally synthesized in the skin upon contact with ultraviolet rays. This vitamin can also be acquired from dietary and nutritional supplements. The active form, vitamin D3, is primarily responsible for calcium homeostasis and bone health. However, many recent studies have associated low levels of vitamin D3 with asthma and food allergies. In this review, we discuss literature to explore the potential that vitamin D3 deficiency may be contributing toward the development of asthma and food allergies. These studies indicate that mothers who supplement with doses of vitamin D3 recommended for daily consumption (400 IU) by the United States Food and Drug Administration is not enough to deliver adequate levels to breastfed infants. Because sufficient vitamin D3 serum levels correlate with a low incidence of asthma and food allergies, high dose vitamin D3 supplementation (4000 IU) by pregnant and breastfeeding women may limit the development of asthma and food allergies in newborns. PMID:27213185

  19. A test of the cerebellar hypothesis of dyslexia in adequate and inadequate responders to reading intervention.

    PubMed

    Barth, Amy E; Denton, Carolyn A; Stuebing, Karla K; Fletcher, Jack M; Cirino, Paul T; Francis, David J; Vaughn, Sharon

    2010-05-01

    The cerebellar hypothesis of dyslexia posits that cerebellar deficits are associated with reading disabilities and may explain why some individuals with reading disabilities fail to respond to reading interventions. We tested these hypotheses in a sample of children who participated in a grade 1 reading intervention study (n = 174) and a group of typically achieving children (n = 62). At posttest, children were classified as adequately responding to the intervention (n = 82), inadequately responding with decoding and fluency deficits (n = 36), or inadequately responding with only fluency deficits (n = 56). Based on the Bead Threading and Postural Stability subtests from the Dyslexia Screening Test-Junior, we found little evidence that assessments of cerebellar functions were associated with academic performance or responder status. In addition, we did not find evidence supporting the hypothesis that cerebellar deficits are more prominent for poor readers with "specific" reading disabilities (i.e., with discrepancies relative to IQ) than for poor readers with reading scores consistent with IQ. In contrast, measures of phonological awareness, rapid naming, and vocabulary were strongly associated with responder status and academic outcomes. These results add to accumulating evidence that fails to associate cerebellar functions with reading difficulties. PMID:20298639

  20. 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

  1. Splenic autotransplantation and the immune system. Adequate testing required for evaluation of effect.

    PubMed Central

    Timens, W; Leemans, R

    1992-01-01

    The risk of severe infections after splenectomy, even after many years, is now well established. In attempts to prevent these infections, spleen-saving techniques, including autotransplantation of spleen fragments, have been performed, when possible in combination with vaccination. The problem in autotransplantation is the evaluation of functional activity. The results of the tests used until now often do not seem to correlate very well with the risk of developing an overwhelming postsplenectomy infection (OPSI). This may be related to the fact that the tests used evaluate general functions, and not specific spleen-related functions, such as the capacity to mount a primary response to certain polysaccharide antigens present in the capsule of bacteria known to cause OPSI. In this review, the significance of the spleen in the human immune system is discussed and the effects of splenectomy are described, including the precautions that can be taken to diminish the risk of postsplenectomy infections and sepsis. It appears that postsplenectomy vaccination is more successful when recently developed protein-conjugated polysaccharide vaccines are used. Because the present testing of the function of spleen autotransplants is not adequate, we suggest that new tests should be developed, employing appropriate polysaccharide antigens. PMID:1543398

  2. Spontaneous 8bp Deletion in Nbeal2 Recapitulates the Gray Platelet Syndrome in Mice

    PubMed Central

    Tomberg, Kärt; Khoriaty, Rami; Westrick, Randal J.; Fairfield, Heather E.; Reinholdt, Laura G.; Brodsky, Gary L.; Davizon-Castillo, Pavel; Ginsburg, David; Di Paola, Jorge

    2016-01-01

    During the analysis of a whole genome ENU mutagenesis screen for thrombosis modifiers, a spontaneous 8 base pair (bp) deletion causing a frameshift in exon 27 of the Nbeal2 gene was identified. Though initially considered as a plausible thrombosis modifier, this Nbeal2 mutation failed to suppress the synthetic lethal thrombosis on which the original ENU screen was based. Mutations in NBEAL2 cause Gray Platelet Syndrome (GPS), an autosomal recessive bleeding disorder characterized by macrothrombocytopenia and gray-appearing platelets due to lack of platelet alpha granules. Mice homozygous for the Nbeal2 8 bp deletion (Nbeal2gps/gps) exhibit a phenotype similar to human GPS, with significantly reduced platelet counts compared to littermate controls (p = 1.63 x 10−7). Nbeal2gps/gps mice also have markedly reduced numbers of platelet alpha granules and an increased level of emperipolesis, consistent with previously characterized mice carrying targeted Nbeal2 null alleles. These findings confirm previous reports, provide an additional mouse model for GPS, and highlight the potentially confounding effect of background spontaneous mutation events in well-characterized mouse strains. PMID:26950939

  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. AMP-activated protein kinase phosphorylates CtBP1 and down-regulates its activity

    SciTech Connect

    Kim, Jae-Hwan; Choi, Soo-Youn; Kang, Byung-Hee; Lee, Soon-Min; Cho, Eun-Jung; Youn, Hong-Duk

    2013-02-01

    Highlights: ► AMPK phosphorylates CtBP1 on serine 158. ► AMPK-mediated phosphorylation of CtBP1 causes the ubiquitination and nuclear export of CtBP1. ► AMPK downregulates the CtBP1-mediated repression of Bax transcription. -- Abstract: CtBP is a transcriptional repressor which plays a significant role in the regulation of cell proliferation and tumor progression. It was reported that glucose withdrawal causes induction of Bax due to the dissociation of CtBP from the Bax promoter. However, the precise mechanism involved in the regulation of CtBP still remains unclear. In this study, we found that an activated AMP-activated protein kinase (AMPK) phosphorylates CtBP1 on Ser-158 upon metabolic stresses. Moreover, AMPK-mediated phosphorylation of CtBP1 (S158) attenuates the repressive function of CtBP1. We also confirmed that triggering activation of AMPK by various factors resulted in an increase of Bax gene expression. These findings provide connections of AMPK with CtBP1-mediated regulation of Bax expression for cell death under metabolic stresses.

  6. 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

  7. 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

  8. Phosphorylated 4E-BP1 is Associated with Poor Survival in Melanoma

    PubMed Central

    O’Reilly, Kathryn E.; Warycha, Melanie; Davies, Michael A.; Rodrik, Vanessa; Zhou, Xi K.; Yee, Herman; Polsky, David; Pavlick, Anna C.; Rosen, Neal; Bhardwaj, Nina; Mills, Gordon; Osman, Iman

    2009-01-01

    Purpose Both the PI3K/AKT and RAS/MAPK signal transduction pathways mediate 4E-BP1 phosphorylation, releasing 4E-BP1 from the mRNA cap and permitting translation initiation. Given the prevalence of PTEN and B-RAF mutations in melanoma, we first examined translation initiation, as measured by phosphorylated 4E-BP1, in metastatic melanoma tissues and cell lines. We then tested the association between amounts of total and phosphorylated 4E-BP1 and patient survival. Experimental Design Seven human metastatic melanoma cells lines and 72 metastatic melanoma patients with accessible metastatic tumor tissues and extended follow up information were studied. Expression of 4E-BP1 transcript, total 4E-BP1 protein, and phosphorylated 4E-BP1 were examined. The relationship between 4E-BP1 transcript and protein expression was assessed in a subset of patient tumors (n=41). The association between total and phospho-4E-BP1 levels and survival was examined in the larger cohort of patients (n=72). Results 4E-BP1 was hyperphosphorylated in 4/7 melanoma cell lines harboring BRAF and PTEN mutations as compared to untransformed melanocytes or RAS/RAF/PTEN wild type melanoma cells. 4E-BP1 transcript correlated with 4E-BP1 total protein levels as measured by the semi-quantitative reverse phase protein array (p=0.012). High levels of phosphorylated 4E-BP1 were associated with worse overall and post-recurrence survival (p=0.02, 0.0003 respectively). Conclusion Our data demonstrate that translation initiation is a common event in human metastatic melanoma and correlates with worse prognosis. Therefore, effective inhibition of the pathways responsible for 4E-BP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients. PMID:19336517

  9. 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.

  10. 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.

  11. 45 CFR 1182.15 - Institute responsibility for maintaining adequate technical, physical, and security safeguards to...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Institute. (2) All records, when not under the personal control of the employees authorized to use the records, must be stored in a locked filing cabinet. Some systems of records are not of such confidential... cards, magnetic tapes, or discs, are not under the personal control of an authorized person,...

  12. 45 CFR 1182.15 - Institute responsibility for maintaining adequate technical, physical, and security safeguards to...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Institute. (2) All records, when not under the personal control of the employees authorized to use the records, must be stored in a locked filing cabinet. Some systems of records are not of such confidential... cards, magnetic tapes, or discs, are not under the personal control of an authorized person,...

  13. 45 CFR 2508.10 - 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... security safeguards to prevent unauthorized disclosure or destruction of manual and automatic record..., and security safeguards to prevent unauthorized disclosure or destruction of manual and...

  14. 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

  15. 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

  16. 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.

  17. 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

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

    2014-05-01

    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

  18. 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

  19. IGF2BP1 promotes mesenchymal cell properties and migration of tumor-derived cells by enhancing the expression of LEF1 and SNAI2 (SLUG)

    PubMed Central

    Zirkel, Anne; Lederer, Marcell; Stöhr, Nadine; Pazaitis, Nikolaos; Hüttelmaier, Stefan

    2013-01-01

    The oncofetal IGF2 mRNA-binding protein 1 (IGF2BP1) controls the migration and invasiveness of primary as well as tumor-derived cells in vitro. Whether the protein also modulates epithelial-mesenchymal-transition (EMT), a hallmark of tumor progression involved in tumor cell dissemination, remained elusive. In this study, we reveal that IGF2BP1 enhances mesenchymal-like cell properties in tumor-derived cells by promoting the expression of the transcriptional regulators LEF1 and SLUG (SNAI2). IGF2BP1 associates with LEF1 transcripts and prevents their degradation in a 3′-UTR-dependent manner resulting in an upregulation of LEF1 expression. LEF1 promotes transcription of the mesenchymal marker fibronectin by associating with the fibronectin 1 promoter. Moreover, LEF1 enforces the synthesis of the ‘EMT-driving’ transcriptional regulator SNAI2. Accordingly, IGF2BP1 knockdown causes MET-like (mesenchymal-epithelial-transition) morphological changes, enhances the formation of cell–cell contacts and reduces cell migration in various mesenchymal-like tumor-derived cells. However, in epithelial-like tumor-derived cells characterized by a lack or low abundance of IGF2BP1, the protein fails to induce EMT. These findings identify IGF2BP1 as a pro-mesenchymal post-transcriptional determinant, which sustains the synthesis of ‘EMT-driving’ transcriptional regulators, mesenchymal markers and enhances tumor cell motility. This supports previous reports, suggesting a role of IGF2BP1 in tumor cell dissemination. PMID:23677615

  20. Silencing of CtBP1 suppresses the migration in human glioma cells.

    PubMed

    Zhao, Chengjin; Shen, Yifen; Tao, Xuelei; Xu, Jian; Lu, Junjie; Liu, Chao; Xu, Zhiwei; Tang, Qing; Tao, Tao; Zhang, Xiubing

    2016-06-01

    Carboxyl-terminal binding protein 1 (CtBP1), up-regulated in various types of human cancers, has been functionally associated with proliferation, anti-apoptosis, and EMT in vitro studies. However, the functional significance of CtBP1 in the pathophysiology of glioma remains unknown. In the present study, we showed the expression of CtBP1 was markedly higher in glioma tissues compared with normal brain tissues by Western blot analysis. Immunohistochemical analysis revealed that CtBP1 mainly localized in the nucleus of glioma cells. Statistical analysis suggested the upregulation of CtBP1 was considerably correlated with the WHO grade (P < 0.05) and those patients with high CtBP1 levels exhibited shorter survival time (P < 0.01). Silencing CtBP1 by short hairpin RNAi caused an inhibition of cell migration. Moreover, knockdown of CtBP1 increases E-cadherin expression and decreases vimentin expression. These data uncovered that CtBP1 protein is a valuable marker of glioma pathogenic process and that CtBP1 can serve as a novel prognostic marker for glioma therapy. PMID:27160109

  1. E4BP4 is a cardiac survival factor and essential for embryonic heart development.

    PubMed

    Weng, Yi-Jiun; Hsieh, Dennis Jine-Yuan; Kuo, Wei-Wen; Lai, Tung-Yuan; Hsu, Hsi-Hsien; Tsai, Chang-Hai; Tsai, Fuu-Jen; Lin, Ding-Yu; Lin, James A; Huang, Chih-Yang; Tung, Kwong-Chung

    2010-07-01

    The bZIP transcription factor E4BP4, has been demonstrated to be a survival factor in pro-B lymphocytes. GATA factors play important roles in transducing the IL-3 survival signal and transactivating the downstream survival gene, E4BP4. In heart, GATA sites are essential for proper transcription of several cardiac genes, and GATA-4 is a mediator of cardiomyocyte survival. However, the role E4BP4 plays in heart is still poorly understood. In this study, Dot-blot hybridization assays using Dig-labeled RNA probes revealed that the E4BP4 gene was expressed in cardiac tissue from several species including, monkey, dog, rabbit, and human. Western blot analysis showed that the E4BP4 protein was consistently present in all of these four species. Furthermore, immunohistochemistry revealed that the E4BP4 protein was overexpressed in diseased heart tissue in comparison with normal heart tissue. In addition, the overexpression of E4BP4 in vitro activated cell survival signaling pathway of cardiomyocytes. At last, siRNA-mediated knock down of E4BP4 in zebrafish resulted in malformed looping of the embryonic heart tube and decreased heart beating. Based on these results, we conclude that E4BP4 plays as a survival factor in heart and E4BP4 is essential for proper embryonic heart development. PMID:20186462

  2. 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

  3. 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

  4. 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

  5. Can loss of balance from mesoscale eddies adequately power deep ocean mixing?

    NASA Astrophysics Data System (ADS)

    Williams, P. D.; Haine, T. W.; Read, P. L.

    2009-12-01

    The global ocean thermohaline circulation is partly composed of the sinking of dense surface waters at high latitudes. But in order to close the circulation and maintain the abyssal stratification, the dense waters must rise up again through vertical mixing. This process requires a source of energy roughly estimated to be 2 TW. Previous work has concluded that tides and winds may adequately supply the required power, but the conceivable role of loss of balance from mesoscale eddies, resulting in the generation of internal inertia-gravity waves and associated vertical mixing, has hitherto been considered to be 'of unknown importance' (Wunsch and Ferrari, 2004). We investigate the potential role of loss of balance, by studying the generation of internal inertia-gravity waves by balanced flow in a rotating two-layer annulus laboratory experiment (Williams et al., 2008). A photograph from the experiment is shown in the figure. As the Rossby number of the balanced flow decreases, the amplitude of the emitted inertia-gravity waves also decreases, but much less rapidly than is predicted by several dynamical theories. This finding suggests that inertia-gravity waves might be far more energised than previously thought. The balanced flow leaks roughly one per cent of its energy each rotation period into internal inertia-gravity waves at the peak of their generation. Crude extrapolation of this result to the global ocean suggests that the flux of energy from mesoscale eddies into internal waves may be as large as 1.5 TW. We claim no accuracy for this figure which is only indicative. Nevertheless, we are persuaded that generation of inertia-gravity waves from the balanced mesoscale flow may be an important source of energy for deep interior mixing, and deserves further study. Reference Williams, PD, Haine, TWN and Read, PL (2008) Inertia-Gravity Waves Emitted from Balanced Flow: Observations, Properties, and Consequences. Journal of the Atmospheric Sciences, 65(11), pp 3543

  6. 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

  7. Human milk feeding supports adequate growth in infants ≤ 1250 grams birth weight

    PubMed Central

    2013-01-01

    Background 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 objective of this study was to evaluate growth velocities and incidence of extrauterine growth restriction in infants ≤ 1250 grams (g) birth weight (BW) receiving an exclusive human milk-based diet with early and rapid advancement of fortification using a donor human milk derived fortifier. Methods In a single center, prospective observational cohort study, preterm infants weighing ≤ 1250 g BW were fed an exclusive human milk-based diet until 34 weeks postmenstrual age. Human milk fortification with donor human milk derived fortifier was started at 60 mL/kg/d and advanced to provide 6 to 8 additional kilocalories per ounce (or 0.21 to 0.28 kilocalories per gram). Data for growth were compared to historical growth standards and previous human milk-fed cohorts. Results We consecutively evaluated 104 infants with mean gestational age of 27.6 ± 2.0 weeks and BW of 913 ± 181 g (mean ± standard deviation). Weight gain was 24.8 ± 5.4 g/kg/day with length 0.99 ± 0.23 cm/week and head circumference 0.72 ± 0.14 cm/week. There were 3 medical NEC cases and 1 surgical NEC case. 22 infants (21%) were small for gestational age at birth. Overall, 45 infants (43%) had extrauterine growth restriction. Weight velocity was affected by day of fortification (p = 0.005) and day of full feeds (p = 0.02). Our cohort had significantly greater growth in weight and length compared to previous entirely human milk-fed cohorts. Conclusions A feeding protocol for infants ≤ 1250 g BW providing an exclusive human milk-based diet with early and rapid advancement of fortification leads to growth meeting targeted standards with a low rate of extrauterine growth restriction. Consistent

  8. 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

  9. 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

  10. 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.

  11. 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

  12. A photometric and spectrographic study of BP Pegasi

    SciTech Connect

    Kim, C.; Mcnamara, D.H.; Joner, M.D. Brigham Young Univ., Provo, UT )

    1989-11-01

    Photometric (uvby beta) and spectrographic observations of the dwarf Cepheid BP Peg are discussed. The observations are used to derive a reddening value of E(b-y) = 0.067 m. An effective temperature of 7470 K, a mean surface gravity, log g = 3.85, and a Fe/H abundance ratio of - 0.08 are obtained. Pulsation theory and stellar model sequences yield M(bol) = 1.4 m, mass = 1.85 solar masses, and age = 1.3 X 10 to the 9th yrs. Also, the radial-velocity data show a mean radial velocity of - 30 km/s and a total velocity range of 36 km/s. 14 refs.

  13. 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

  14. Trypanosoma cruzi: specific detection of parasites by PCR in infected humans and vectors using a set of primers (BP1/BP2) targeted to a nuclear DNA sequence.

    PubMed

    Silber, A M; Búa, J; Porcel, B M; Segura, E L; Ruiz, A M

    1997-03-01

    In the present work we evaluate Trypanosoma cruzi DNA detection by PCR using the nuclear oligonucleotides BP1/BP2 as primers. These primers are targeted to the 5' and 3' ends of the coding region for the flagellar protein F29. An amplification product of BP1/BP2 is a DNA band 692 bp long. Titration assays were performed to evaluate the minimum amount of parasite DNA that can be detected by this assay, resulting in 10 fg (equivalent to about 1/20 of the genome). The assay was also performed using T. cruzi DNA from different strains, clones, and human-derived isolates obtaining, in all cases, amplification products. No DNA amplification was observed when the PCR was performed using DNA from Leishmania braziliensis, but when T. rangeli DNA was used, a 615-bp-long fragment was amplified. Under appropriate gel conditions T. cruzi and T. rangeli DNA amplicons could be differentiated. When both conventional xenodiagnosis and PCR detection of parasite DNA in the feces of insect vectors fed with blood from infected patients were compared, 10 of 20 samples were positive by both techniques. However, 2 other samples with positive serology were also positive by PCR. When PCR was performed on blood samples from infected and uninfected individuals, 62 of 65 serologically positive human samples amplified the BP1/BP2 692-bp T. cruzi DNA fragment (sensitivity >95%). The 3 negative samples were positive when Southern blot hybridization was performed using the radiolabeled PCR amplification product as probe (sensitivity 100%). PMID:9085919

  15. Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

    PubMed Central

    Gibbs-Seymour, Ian; Markiewicz, Ewa; Bekker-Jensen, Simon; Mailand, Niels; Hutchison, Christopher J

    2015-01-01

    Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in order to facilitate its rapid recruitment to sites of DNA damage and could explain why an absence of lamin A/C accelerates aging. PMID:25645366

  16. 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

  17. Nephrotic-range proteinuria is strongly associated with poor blood pressure control in pediatric chronic kidney disease.

    PubMed

    Kogon, Amy J; Pierce, Christopher B; Cox, Christopher; Brady, Tammy M; Mitsnefes, Mark M; Warady, Bradley A; Furth, Susan L; Flynn, Joseph T

    2014-04-01

    Despite the importance of blood pressure (BP) control in chronic kidney disease (CKD), few longitudinal studies on its trends exist for pediatric patients with CKD. Here we longitudinally analyzed casual data in 578 children with CKD and annual BP measurements standardized for age, gender, and height. At baseline, 124 children were normotensive, 211 had elevated BP, and 243 had controlled hypertension. Linear mixed-effects models accounting for informative dropout determined factors associated with BP changes over time and relative sub-hazards (RSH) identified factors associated with the achievement of controlled BP in children with baseline elevated BP. Younger age, black children, higher body mass index, and higher proteinuria at baseline were associated with higher standardized BP levels. Overall average BP decreased during follow-up, but nephrotic-range proteinuria and increased proteinuria and body mass index were risk factors for increasing BP over time. Only 46% of hypertensive patients achieved controlled BP during follow-up; least likely were those with nephrotic-range proteinuria (RSH 0.19), black children (RSH 0.42), and children with baseline glomerular filtration rate under 40 ml/min per 1.73 m(2) (RSH 0.58). Thus, of many coexisting factors, nephrotic-range proteinuria was most strongly associated with poor BP control and worsening BP over time. Future research should focus on strategies to reduce proteinuria, as this may improve BP control and slow the progression of CKD. PMID:24048375

  18. 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

  19. CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly

    PubMed Central

    Moree, Ben; Meyer, Corey B.; Fuller, Colin J.

    2011-01-01

    Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). Understanding how CENP-A chromatin is assembled and maintained is central to understanding chromosome segregation mechanisms. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. These factors localize to centromeres in telophase/G1, when new CENP-A chromatin is assembled. The mechanisms that control their targeting are unknown. In this paper, we identify a mechanism for recruiting the Mis18 complex protein M18BP1 to centromeres. We show that depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly. We find that M18BP1 directly binds CENP-C through conserved domains in the CENP-C protein. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly. PMID:21911481

  20. CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly.

    PubMed

    Moree, Ben; Meyer, Corey B; Fuller, Colin J; Straight, Aaron F

    2011-09-19

    Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). Understanding how CENP-A chromatin is assembled and maintained is central to understanding chromosome segregation mechanisms. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. These factors localize to centromeres in telophase/G1, when new CENP-A chromatin is assembled. The mechanisms that control their targeting are unknown. In this paper, we identify a mechanism for recruiting the Mis18 complex protein M18BP1 to centromeres. We show that depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly. We find that M18BP1 directly binds CENP-C through conserved domains in the CENP-C protein. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly. PMID:21911481

  1. HLA-G 14-bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

    PubMed

    Genre, J; Reginaldo, F P Santos; Andrade, J Marco de Leon; Lima, F P; da Camara, A V Coutinho; Donadi, E A; Crispim, J C

    2016-01-01

    H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection. PMID:26368842

  2. Association of large scale 4977-bp “common” deletions in sperm mitochondrial DNA with asthenozoospermia and oligoasthenoteratozoospermia

    PubMed Central

    Ambulkar, Prafulla S.; Chuadhari, Ajay R.; Pal, Asoke K.

    2016-01-01

    OBJECTIVE: To determine the association of large-scale mitochondrial DNA (mtDNA) deletions with abnormal sperm or abnormal flagellar movement of human spermatozoa in asthenozoospermia and oligoasthenoteratozoospermia (OAT) subjects using percoll gradients fractionation and long-range polymerase chain reaction (PCR). DESIGN: We investigated sixty infertile men and thirty normal healthy fertile controls. Of sixty infertile men, 39 were asthenozoospermia and 21 were OAT. MATERIALS AND METHODS: Percoll gradients discontinuous technique was used for separation of spermatozoa on the basis of their motility. Long-range PCR was used for detection of “common” 4977-bp deletions, and primer shift technique was used for confirmation of deletions. RESULTS: Overall fourteen subjects (14/60; 23.3%) of which eight (8/39; 20.5%) asthenozoospermia and six (6/21; 28.6%) OAT had shown deletions of 4977-bp. Deletions were more common (23.3%) in 40% fraction than 60% (11.6%) and 80% (5%) fractions. Sequencing results had shown deleted region of mtDNA. CONCLUSION: Abnormal spermatozoa had more number of mtDNA deletions than normal sperm, and abnormal spermatozoa had lost genes for the oxidative phosphorylation. Our findings suggest that large-scale 4977-bp mtDNA deletions in the spermatozoa from the infertile subjects cause the asthenozoospermic and OAT pathophysiological conditions in infertile males. PMID:27110076

  3. Tissue-specific regulation of 4E-BP1 and S6K1 phosphorylation by alpha-ketoisocaproate.

    PubMed

    Yoshizawa, Fumiaki; Sekizawa, Haruhito; Hirayama, Sachiyo; Yamazaki, Yasuhiro; Nagasawa, Takashi; Sugahara, Kunio

    2004-02-01

    The indispensable branched-chain amino acid leucine acts as a key regulator of mRNA translation by modulating the phosphorylation of proteins that represent important control points in translation initiation, including the translational repressor, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1). In the current study, we compared the effects of L- and D-enantiomers of leucine on the phosphorylation of 4E-BP1 and S6K1. We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate (alpha-KIC), mediates the effects of leucine. Food-deprived (18 h) rats were orally administered 135 mg/100 g body weight L-leucine, D-leucine or alpha-KIC and were sacrificed after 1 h. L-Leucine administration had an obvious stimulatory effect on the phosphorylation of 4E-BP1 and S6K1 in both skeletal muscle and liver while D-leucine was much less effective, indicating that the effect of leucine is stereospecific. Oral administration of alpha-KIC mimicked the stimulatory effect of L-leucine in skeletal muscle. In contrast to skeletal muscle, provision of alpha-KIC was significantly less effective than L-leucine in the liver. The results showing that the efficacy of L-leucine and alpha-KIC in stimulating phosphorylation of S6K1 and 4E-BP1 is equivalent in skeletal muscle, may be explained by the conversion of alpha-KIC to L-leucine. PMID:15228219

  4. Multiple PAR and E4BP4 bZIP transcription factors in zebrafish: diverse spatial and temporal expression patterns.

    PubMed

    Ben-Moshe, Zohar; Vatine, Gad; Alon, Shahar; Tovin, Adi; Mracek, Philipp; Foulkes, Nicholas S; Gothilf, Yoav

    2010-09-01

    Circadian rhythms of physiology and behavior are generated by an autonomous circadian oscillator that is synchronized daily with the environment, mainly by light input. The PAR subfamily of transcriptional activators and the related E4BP4 repressor belonging to the basic leucine zipper (bZIP) family are clock-controlled genes that are suggested to mediate downstream circadian clock processes and to feedback onto the core oscillator. Here, the authors report the characterization of these genes in the zebrafish, an increasingly important model in the field of chronobiology. Five novel PAR and six novel e4bp4 zebrafish homolog genes were identified using bioinformatic tools and their coding sequences were cloned. Based on their evolutionary relationships, these genes were annotated as ztef2, zhlf1 and zhlf2, zdbp1 and zdbp2, and ze4bp4-1 to -6. The spatial and temporal mRNA expression pattern of each of these factors was characterized in zebrafish embryos in the context of a functional circadian clock and regulation by light. Nine of the factors exhibited augmented and rhythmic expression in the pineal gland, a central clock organ in zebrafish. Moreover, these genes were found to be regulated, to variable extents, by the circadian clock and/or by light. Differential expression patterns of multiple paralogs in zebrafish suggest multiple roles for these factors within the vertebrate circadian clock. This study, in the genetically accessible zebrafish model, lays the foundation for further research regarding the involvement and specific roles of PAR and E4BP4 transcription factors in the vertebrate circadian clock mechanism. PMID:20854132

  5. About the {open_quotes}Asian{close_quotes}-specific 9-bp deletion of mtDNA...

    SciTech Connect

    Torroni, A.; Petrozzi, M.; Santolamazza, P.

    1995-08-01

    The 9-bp deletion between the COII and tRNA{sup Lys} genes is due to the lack of one of two adjacent copies of a 9-bp sequence usually present in human mtDNA. This mutation is very common in Asians and populations of Asian ancestry (e.g., Polynesians and Amerinds) and often has been considered and ethnic-specific polymorphism for these populations. We now report the detection of the COII-tRNA{sup Lys} 9-bp deletion in an individual of Italian descent. To our knowledge, this is the first time that the 9-bp deletion has been observed in Europeans. 19 refs.

  6. 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.

  7. Phytase improves apparent total tract digestibility of phosphorus and calcium in piglets fed diets with adequate or reduced phosphorus content.

    PubMed

    Kühn, I; Partanen, K

    2012-12-01

    The effect of a thermotolerant 6-phytase produced by Trichoderma reesei on performance and apparent total tract digestibility (ATTD) of P and Ca was evaluated in 192 weaned piglets (randomized block design; 16 replicates; 2 piglets each). Diets based on wheat (Triticum aestivum), barley (Hordeum vulgare), oat (Avena sativa), soybean (Glycine max) meal, and whey protein with adequate [positive control (PC)] or reduced [negative control (NC)] Ca and P levels were fed for 46 d after weaning. The PC and NC diets contained 8.0 and 6.4 g/kg Ca and 2.9 and 1.9 g/kg digestible P, respectively. Pelleted diets contained 0, 500, or 1000 phytase units (FTU)/kg. Growth performance and G:F were measured during starter (25 d) and weaner pig (21 d) periods. The ATTD of Ca and P was determined by spot sampling at the end of the weaner pig period (8 pens per treatment over 5 consecutive d). Data were analyzed using a mixed model with random block effect and fixed effect of dietary P and phytase level and their interaction. Dietary P level did not affect ADG or G:F of piglets over the entire feeding period (P > 0.10) whereas phytase increased G:F (P < 0.05). During the starter period, phytase linearly enhanced (P < 0.05) ADG (258, 266, and 292 g) and G:F (639, 677, and 664 g gain/kg feed DM) without further increase in the weaner pig period (P > 0.10). A P × phytase interaction (P < 0.05) was observed for ATTD of P, more so for NC (48, 61, and 68%, respectively) than PC diets (52, 62, and 61%). The ATTD of Ca was higher (P < 0.05) for PC than NC diets (68 vs. 58%) and increased quadratically by phytase (61, 65, and 63%). In conclusion, the phytase tested enhanced piglet performance during the postweaning period and increased ATTD of P and Ca. PMID:23365327

  8. 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.

  9. 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

  10. [The pregnant employee in anaesthesia and intensive care - An evidence-based approach to designing adequate workplaces].

    PubMed

    Röher, Katharina; Göpfert, Matthias S

    2015-07-01

    In the light of a rising percentage of women among employees in anaesthesia and intensive care designing adequate workplaces for pregnant employees plays an increasingly important role. Here it is necessary to align the varied interests of the pregnant employee, fellow employees and the employer, where the legal requirements of the Maternity Protection Act ("Mutterschutzgesetz") form the statutory framework. This review describes how adequate workplaces for pregnant employees in anaesthesia and intensive care can be established considering the scientific evidence on the subject. PMID:26230896

  11. 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

  12. 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

  13. Survey and Rapid Detection of Bordetella pertussis in Clinical Samples Targeting the BP485 in China

    PubMed Central

    Liu, Wei; Xu, Yinghua; Dong, Derong; Li, Huan; Zhao, Xiangna; Li, Lili; Zhang, Ying; Wei, Xiao; Wang, Xuesong; Huang, Simo; Zeng, Ming; Huang, Liuyu; Zhang, Shumin; Yuan, Jing

    2015-01-01

    Bordetella pertussis is an important human respiratory pathogen. Here, we describe a loop-mediated isothermal amplification (LAMP) method for the rapid detection of B. pertussis in clinical samples based on a visual test. The LAMP assay detected the BP485 target sequence within 60 min with a detection limit of 1.3 pg/μl, a 10-fold increase in sensitivity compared with conventional PCR. All 31 non-pertussis respiratory pathogens tested were negative for LAMP detection, indicating the high specificity of the primers for B. pertussis. To evaluate the application of the LAMP assay to clinical diagnosis, of 105 sputum and nasopharyngeal samples collected from the patients with suspected respiratory infections in China, a total of 12 B. pertussis isolates were identified from 33 positive samples detected by LAMP-based surveillance targeting BP485. Strikingly, a 4.5 months old baby and her mother were found to be infected with B. pertussis at the same time. All isolates belonged to different B. pertussis multilocus sequence typing groups with different alleles of the virulence-related genes including four alleles of ptxA, six of prn, four of tcfA, two of fim2, and three of fim3. The diversity of B. pertussis carrying toxin genes in clinical strains indicates a rapid and continuing evolution of B. pertussis. This combined with its high prevalence will make it difficult to control. In conclusion, we have developed a visual detection LAMP assay, which could be a useful tool for rapid B. pertussis detection, especially in situations where resources are poor and in point-of-care tests. PMID:25798436

  14. 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

  15. Mood lability among offspring of parents with bipolar disorder and community controls

    PubMed Central

    Birmaher, Boris; Goldstein, Benjamin I; Axelson, David A; Monk, Kelly; Hickey, Mary Beth; Fan, Jieyu; Iyengar, Satish; Ha, Wonho; Diler, Rasim S; Goldstein, Tina; Brent, David; Ladouceur, Cecile D; Sakolsky, Dara; Kupfer, David J

    2013-01-01

    Objectives Early identification of bipolar disorder (BP) symptomatology is crucial for improving the prognosis of this illness. Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study. Methods Forty-one school-age BP offspring of 38 BP parents, 257 healthy or non-BP offspring of 174 BP parents, and 192 offspring of 117 control parents completed a scale that was developed to evaluate mood lability in youth, i.e., the Children’s Affective Lability Scale (CALS). Results A factor analysis of the parental CALS, and in part the child CALS, revealed Irritability, Mania, and Anxiety/Depression factors, with most of the variance explained by the Irritability factor. After adjusting for confounding factors (e.g., parental and offspring non-BP psychopathology), BP offspring of BP parents showed the highest parental and child total and factor scores, followed by the non-BP offspring of BP parents, and then the offspring of the controls. Conclusions Mood lability overall and mania-like, anxious/depressed, and particularly irritability symptoms may be a prodromal phenotype of BP among offspring of parents with BP. Prospective studies are warranted to clarify whether these symptoms will predict the development of BP and/or other psychopathology. If confirmed, these symptoms may become a target of treatment and biological studies before BP develops. PMID:23551755

  16. 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. PMID:26202804

  17. Lyapunov Exponent Criterion in the CR3BP

    NASA Astrophysics Data System (ADS)

    Quarles, Billy; Eberle, Jason; Cuntz, Manfred; Musielak, Zdzislaw

    2010-10-01

    Our specific focus is to describe the motion of an extra solar planet in a binary star system. We aim to accomplish this by using the methods of chaos theory as an alternate method to our previously established Hodograph method in the circular restricted 3-body problem (CR3BP). Previously Eberle et al. (2010) has shown that a parameter space exists depending only on the mass ratio μ and distance ratio ρo which allowed them to identify regions of stability. Our method will validate the previous results while also providing more information relating to the presence of resonances and their effects on orbital stability. We extend the previous studies by increasing the simulation time, applying the method of Lyapunov exponents, calculating the time series spectrum of the orbit, and determining the Lyapunov dimension. The obtained results demonstrate when a system becomes unstable by orbital energy criterion and the method of Lyapunov exponents provides a quantitative classification scale to characterize the instability. By applying the maximum Lyapunov exponent (MLE) to the parameter space, we determine a region of stability with MLE values larger than the surrounding region. The time series spectra and the Lyapunov Dimension methods are used to illustrate the reasons behind the stability plateau which eludes to the resonance phenomena.

  18. 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

  19. 21 CFR 1.283 - What happens to food that is imported or offered for import without adequate prior notice?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... dealt with as set forth in CBP regulations relating to general order merchandise (19 CFR part 127... 21 Food and Drugs 1 2010-04-01 2010-04-01 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...

  20. 21 CFR 1.284 - What are the other consequences of failing to submit adequate prior notice or otherwise failing...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What are the other consequences of failing to submit adequate prior notice or otherwise failing to comply with this subpart? 1.284 Section 1.284 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL...

  1. 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…

  2. 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. …

  3. Students' Use of Tutoring Services, by Adequate Yearly Progress Status of School. Statistics in Brief. NCES 2010-023

    ERIC Educational Resources Information Center

    Warkentien, Siri; Grady, Sarah

    2009-01-01

    This Statistics in Brief contributes to current research by investigating the use of tutoring services among a nationally representative group of public school students enrolled in grades K-12. The report compares students in schools that have not made Adequate Yearly Progress (AYP) for 3 or more years, and were thereby enrolled in schools that…

  4. 33 CFR 151.2065 - What is the standard of adequate compliance determined by the ANSTF for this subpart? [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false What is the standard of adequate... Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management...

  5. 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

  6. 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

  7. Funding an Adequate Education for America's Youth: A Plan for Melding Political and Market Definitions of Educational Adequacy.

    ERIC Educational Resources Information Center

    Guthrie, James W.

    Noting that American society has conventionally relied on both the political process and the marketplace to arrive at a "definition" of adequate education, but that the political process fails to account for individual preferences while the marketplace can cater to many individual preferences, this paper attempts to combine the two processes in a…

  8. 36 CFR 79.9 - Standards to determine when a repository possesses the capability to provide adequate long-term...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Standards to determine when a repository possesses the capability to provide adequate long-term curatorial services. 79.9 Section 79.9 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR CURATION OF FEDERALLY-OWNED AND...

  9. 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…

  10. Evaluating Rural Progress in Mathematics Achievement: Is "Adequate Yearly Progress" (AYP) Feasible, Valid, Reliable, and Fair? Working Paper.

    ERIC Educational Resources Information Center

    Lee, Jaekyung

    The No Child Left Behind Act requires standards-based accountability for school districts and schools receiving Title I funds. A major component of this policy is to report whether districts and schools are making "adequate yearly progress" (AYP) based on their performance goals. This paper raises questions for rural schools using the National…

  11. Role of Transcriptional Corepressor CtBP1 in Prostate Cancer Progression12

    PubMed Central

    Wang, Rui; Asangani, Irfan A; Chakravarthi, Balabhadrapatruni VSK; Ateeq, Bushra; Lonigro, Robert J; Cao, Qi; Mani, Ram-Shankar; Camacho, Daniel F; McGregor, Natalie; Schumann, Taibriana EW; Jing, Xiaojun; Menawat, Radhika; Tomlins, Scott A; Zheng, Heng; Otte, Arie P; Mehra, Rohit; Siddiqui, Javed; Dhanasekaran, Saravana M; Nyati, Mukesh K; Pienta, Kenneth J; Palanisamy, Nallasivam; Kunju, Lakshmi P; Rubin, Mark A; Chinnaiyan, Arul M; Varambally, Sooryanarayana

    2012-01-01

    Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. In this study, we observed the overexpression and mislocalization of CtBP1 in metastatic prostate cancer and demonstrated the functional significance of CtBP1 in prostate cancer progression. Transient and stable knockdown of CtBP1 in prostate cancer cells inhibited their proliferation and invasion. Expression profiling studies of prostate cancer cell lines revealed that multiple tumor suppressor genes are repressed by CtBP1. Furthermore, our studies indicate a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. In vivo studies using chicken chorioallantoic membrane assay, xenograft studies, and murine metastasis models suggested a role for CtBP1 in prostate tumor growth and metastasis. Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression and may serve as a viable therapeutic target. PMID:23097625

  12. 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...

  13. 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...

  14. 78 FR 53137 - Flint Hills Resources Alaska, LLC, BP Pipelines (Alaska) Inc., ConocoPhillips Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ... formal complaint against BP Pipelines (Alaska) Inc., ConocoPhillips Transportation Alaska, Inc., and... Energy Regulatory Commission Flint Hills Resources Alaska, LLC, BP Pipelines (Alaska) Inc., ConocoPhillips Transportation Alaska, Inc., ExxonMobil Pipeline Company; Notice of Complaint Take notice that...

  15. 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

  16. 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.

  17. 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

    ..., and mitigate the impact of, any oil spills associated with offshore drilling in the future. The... 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...

  18. 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

    ... spill and develop options to guard against, and mitigate the impact of, any oil spills associated with... 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...

  19. 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

    ..., and mitigate the impact of, any oil spills associated with offshore drilling in the future. The... 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...

  20. 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....

  1. 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....

  2. 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

  3. Factors associated with adequate weekly reporting for disease surveillance data among health facilities in Nairobi County, Kenya, 2013

    PubMed Central

    Mwatondo, Athman Juma; Ng'ang'a, Zipporah; Maina, Caroline; Makayotto, Lyndah; Mwangi, Moses; Njeru, Ian; Arvelo, Wences

    2016-01-01

    Introduction Kenya adopted the Integrated Disease Surveillance and Response (IDSR) strategy in 1998 to strengthen disease surveillance and epidemic response. However, the goal of weekly surveillance reporting among health facilities has not been achieved. We conducted a cross-sectional study to determine the prevalence of adequate reporting and factors associated with IDSR reporting among health facilities in one Kenyan County. Methods Health facilities (public and private) were enrolled using stratified random sampling from 348 facilities prioritized for routine surveillance reporting. Adequately-reporting facilities were defined as those which submitted >10 weekly reports during a twelve-week period and a poor reporting facilities were those which submitted <10 weekly reports. Multivariate logistic regression with backward selection was used to identify risk factors associated with adequate reporting. Results From September 2 through November 30, 2013, we enrolled 175 health facilities; 130(74%) were private and 45(26%) were public. Of the 175 health facilities, 77 (44%) facilities classified as adequate reporting and 98 (56%) were reporting poorly. Multivariate analysis identified three factors to be independently associated with weekly adequate reporting: having weekly reporting forms at visit (AOR19, 95% CI: 6-65], having posters showing IDSR functions (AOR8, 95% CI: 2-12) and having a designated surveillance focal person (AOR7, 95% CI: 2-20). Conclusion The majority of health facilities in Nairobi County were reporting poorly to IDSR and we recommend that the Ministry of Health provide all health facilities in Nairobi County with weekly reporting tools and offer specific trainings on IDSR which will help designate a focal surveillance person. PMID:27303581

  4. 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

  5. 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.

  6. E4BP4: an unexpected player in the immune response.

    PubMed

    Male, Victoria; Nisoli, Ilaria; Gascoyne, Duncan M; Brady, Hugh J M

    2012-02-01

    Until recently, the basic leucine zipper transcription factor E4BP4 (also known as NFIL3) was of little interest to immunologists, being best known for its role in regulating circadian rhythm in chick pineal gland. However, characterisation of E4bp4(-/-) mice, independently generated in four different laboratories, has revealed roles for E4BP4 in diverse haematopoietic lineages. E4BP4 is essential for the development of NK cells and CD8α(+) conventional dendritic cells, and is also involved in macrophage activation, polarisation of CD4(+) T cell responses and B cell class switching to IgE. Here, we discuss the role of E4BP4 as a regulator of the immune response and highlight future questions for the field. PMID:22075207

  7. Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary?

    PubMed

    Bischoff-Ferrari, Heike

    2009-12-01

    Strong evidence indicates that many or most adults in the United States and Europe would benefit from vitamin D supplements with respect to fracture and fall prevention, and possibly other public health targets, such as cardiovascular health, diabetes and cancer. This review discusses the amount of vitamin D supplementation needed and a desirable 25-hydroxyvitamin D level to be achieved for optimal musculoskeletal health. Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. Two most recent meta-analyses of double-blind randomised controlled trials came to the conclusion that vitamin D reduces the risk of falls by 19%, the risk of hip fracture by 18% and the risk of any non-vertebral fracture by 20%; however, this benefit was dose dependent. Fall prevention was only observed in a trial of at least 700 IU vitamin D per day, and fracture prevention required a received dose (treatment dose*adherence) of more than 400 IU vitamin D per day. Anti-fall efficacy started with achieved 25-hydroxyvitamin D levels of at least 60 nmol l(-1) (24 ng ml(-1)) and anti-fracture efficacy started with achieved 25-hydroxyvitamin D levels of at least 75 nmol l(-1) (30 ng ml(-1)) and both endpoints improved further with higher achieved 25-hydroxyvitamin D levels. Founded on these evidence-based data derived from the general older population, vitamin D supplementation should be at least 700-1000 IU per day and taken with good adherence to cover the needs for both fall and fracture prevention. Ideally, the target range for 25-hydroxyvitamin D should be at least 75 nmol l(-1), which may need more than 700-1000 IU vitamin D in individuals with severe vitamin D deficiency or those overweight. PMID:19945690

  8. Is fine-needle aspiration diagnosis of malignancy adequate prior to major lung resections including pneumonectomy?

    PubMed

    Khorsandi, Maziar; Shaikhrezai, Kasra; Wallace, William; Brackenbury, Edward

    2012-08-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether a fine-needle aspiration (FNA) diagnosis is of sufficient reliability for the diagnosis of lung cancer prior to a major lung resection. Altogether, 112 papers were found using the reported search, of which 13 papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The tabulated studies include two meta-analyses, one systematic review, one randomized controlled trial (RCT) and nine cohort studies. The specificity reported for FNA in the diagnosis and staging of lung cancer ranged from 96.2 to 100%. One meta-analysis reported a specificity of 97%. Another meta-analysis reported a specificity of 98.8%. A systematic review reported a specificity of 97%. An RCT reported a specificity of 96.2-100%. We conclude that the FNA for lung cancer is reported to be highly specific prior to major lung resection with a very low false positive rate. However, although a false positive may occasionally be acceptable in lobectomies, where the lobes are often removed without histology, all steps should be taken to avoid a false positive result in pneumonectomy considering the serious consequences of embarking upon such an operation in the small number of patients with a false positive result, and we recommend that a positive FNA result should be confirmed by means of alternative sampling methods. We also acknowledge that obtaining an additional biopsy specimen would add to the risk of morbidity and costs; therefore, any benefits should be weighed against risks and additional costs. PMID:22611184

  9. 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

  10. 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

  11. 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

  12. Oncofetal protein IGF2BP3 facilitates the activity of proto-oncogene protein eIF4E through the destabilization of EIF4E-BP2 mRNA.

    PubMed

    Mizutani, R; Imamachi, N; Suzuki, Y; Yoshida, H; Tochigi, N; Oonishi, T; Suzuki, Y; Akimitsu, N

    2016-07-01

    RNA-binding proteins (RBPs) have important roles in tumorigenesis. Although IGF2BP3, an evolutionally conserved RBP, has been reported as a useful diagnostic marker for various cancers and has been considered a regulator of tumorigenesis, little is known of the function of IGF2BP3 because of lack of information regarding IGF2BP3 target mRNAs. Here, we report the identification of IGF2BP3 target mRNAs and IGF2BP3 function in cancer proliferation. We identified mRNAs with altered expression in IGF2BP3-depleted cells by massive sequencing analysis and IGF2BP3-binding RNAs by immunoprecipitation of IGF2BP3 followed by massive sequencing analysis, resulting in the identification of 110 candidates that are negatively regulated by IGF2BP3. We found that IGF2BP3 destabilized EIF4E-BP2 and MEIS3 mRNAs. Co-immunoprecipitation analysis revealed the interaction between IGF2BP3 and ribonucleases such as XRN2 and exosome component. The retarded proliferation of IGF2BP3-depleted cells was partially rescued by the depletion of EIF4E-BP2, which negatively regulates eukaryotic translation initiation factor 4E (eIF4E), an activator of translation and a well-known proto-oncogene. Consistent with this observation, IGF2BP3 depletion reduced phosphorylated eIF4E, the active form, and translational efficiency of eIF4E target transcripts. Reduction of phosphorylated eIF4E by IGF2BP3 depletion was rescued by EIF4E-BP2 depletion. At last, we found an inverse correlation between the expression level of IGF2BP3 and EIF4E-BP2 in human lung adenocarcinoma tissues. Together, these results suggest that IGF2BP3 promotes eIF4E-mediated translational activation through the reduction of EIF4E-BP2 via mRNA degradation, leading to enhanced cell proliferation. This is the first report demonstrating that IGF2BP3 is an RNA-destabilizing factor. Notably, here we provide the first evidence for the functional linkage between two previously well-known cancer biomarkers, IGF2BP3 and eIF4E. PMID:26522719

  13. 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).

  14. CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells

    PubMed Central

    Niu, Ying-Lin; Li, Ya-Jun; Wang, Jing-Bo; Lu, Yuan-Yuan; Liu, Zhen-Xiong; Feng, Shan-Shan; Hu, Jian-Guo; Zhai, Hui-Hong

    2016-01-01

    AIM: To investigate the mechanism of calcyclin binding protein/Siah-1 interacting protein (CacyBP/SIP) nuclear translocation in promoting the proliferation of gastric cancer (GC) cells. METHODS: The effect of CacyBP/SIP nuclear translocation on cell cycle was investigated by cell cycle analysis. Western blot analysis was used to assess the change in expression of cell cycle regulatory proteins and proteasome-mediated degradation of p27Kip1. Co-immunoprecipitation (co-IP) analysis was performed to examine the binding of CacyBP/SIP with Skp1. A CacyBP/SIP truncation mutant which lacked the Skp1 binding site was constructed and fused to a fluorescent protein. Subsequently, the effect on Skp1 binding with the fusion protein was examined by co-IP, while localization of fluorescent fusion protein observed by confocal laser microscopy, and change in p27Kip1 protein expression assessed by Western blot analysis. RESULTS: CacyBP/SIP nuclear translocation induced by gastrin promoted progression of GC cells from G1 phase. However, while CacyBP/SIP nuclear translocation was inhibited using siRNA to suppress CacyBP/SIP expression, cell cycle was clearly inhibited. CacyBP/SIP nuclear translocation significantly decreased the level of cell cycle inhibitor p27Kip1, increased Cyclin E protein expression whereas the levels of Skp1, Skp2, and CDK2 were not affected. Upon inhibition of CacyBP/SIP nuclear translocation, there were no changes in protein levels of p27Kip1 and Cyclin E, while p27Kip1 decrease could be prevented by the proteasome inhibitor MG132. Moreover, CacyBP/SIP was found to bind to Skp1 by immunoprecipitation, an event that was abolished by mutant CacyBP/SIP, which also failed to stimulate p27Kip1 degradation, even though the mutant could still translocate into the nucleus. CONCLUSION: CacyBP/SIP nuclear translocation contributes to the proliferation of GC cells, and CacyBP/SIP exerts this effect, at least in part, by stimulating ubiquitin-mediated degradation of p27

  15. 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.

  16. Subepidermal Blistering Induced by Human Autoantibodies to BP180 Requires Innate Immune Players in a Humanized Bullous Pemphigoid Mouse Model

    PubMed Central

    Liu, Zhi; Sui, Wen; Zhao, Minglang; Li, Zhuowei; Li, Ning; Thresher, Randy; Giudice, George J.; Fairley, Janet A.; Sitaru, Cassian; Zillikens, Detlef; Ning, Gang; Marinkovich, Peter; Diaz, Luis A.

    2008-01-01

    Bullous pemphigoid (BP) is a cutaneous autoimmune inflammatory disease associated with subepidermal blistering and autoantibodies against BP180, a transmembrane collagen and major component of the hemidesmosome. Numerous inflammatory cells infiltrate the upper dermis in BP. IgG autoantibodies in BP fix complement and target multiple BP180 epitopes that are highly clustered within a non-collagen linker domain, termed NC16A. Anti-BP180 antibodies induce BP in mice. In this study, we generated a humanized mouse strain, in which the murine BP180NC14A is replaced with the homologous human BP180NC16A epitope cluster region. We show that the humanized NC16A (NC16A+/+) mice injected with anti-BP180NC16A autoantibodies develop BP-like subepidermal blisters. The F(ab′)2 fragments of pathogenic IgG fail to activate complement cascade and are no longer pathogenic. The NC16A+/+ mice pretreated with mast cell activation blocker or depleting of complement or neutrophils become resistant to BP. These findings suggest that the humoral response in BP critically depends on innate immune system players. PMID:18922680

  17. Physician/Pharmacist Collaboration to Improve Blood Pressure Control

    PubMed Central

    Carter, Barry L.; Ardery, Gail; Dawson, Jeffrey D.; James, Paul A.; Bergus, George R.; Doucette, William R.; Chrischilles, Elizabeth A.; Franciscus, Carrie L.; Xu, Yinghui

    2010-01-01

    Background Studies have demonstrated that blood pressure (BP) control can be improved when clinical pharmacists assist with patient management. The purpose of this study was to evaluate the effectiveness of a physician/pharmacist intervention to improve BP control. Methods This was a prospective, cluster-randomized controlled clinical trial with clinics randomized to control (n=3) or intervention (n=3) groups. The study enrolled 402 patients with uncontrolled hypertension (mean age 58.3 years). Clinical pharmacists made drug-therapy recommendations to physicians based on national guidelines. Research nurses performed BP measurements and 24-hour BP monitoring. Results Guideline adherence scores increased from 49.4 ± 19.3 at baseline to 53.4 ± 18.1 at 6 months (9% increase) in the control group and from 40.4 ± 22.6 to 62.8 ± 13.5 (57% increase) in the intervention group (p=0.089 adjusted comparison between groups). Mean BP decreased 6.8/4.5 and 20.7/9.7 mm Hg in the control and intervention groups, respectively, (p<0.05 for between-group systolic BP (SBP) comparison). The adjusted difference in SBP was −12.0 (95% CI: −24.0, 0.0) mm Hg, while the difference in diastolic BP (DBP) was −1.8 (CI: −11.9, 8.3). The 24-hour BP levels showed similar effect sizes. BP was controlled in 29.9% of patients in the control group and 63.9% in the intervention group (adjusted odds ratio 3.2; CI: 2.0, 5.1; p<0.001). Conclusions A physician/pharmacist collaborative intervention achieved significantly better mean BP and overall BP control rates when compared to a control group. Additional research should be conducted to evaluate efficient strategies to implement team-based chronic disease management. PMID:19933962

  18. 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.

  19. 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

  20. Exhaustive exercise increases inflammatory response via Toll like receptor-4 and NF-κBp65 pathway in rat adipose tissue.

    PubMed

    Rosa, José C; Lira, Fábio S; Eguchi, Ricardo; Pimentel, Gustavo D; Venâncio, Daniel P; Cunha, Cláudio A; Oyama, Lila M; De Mello, Marco T; Seelaender, Marília; do Nascimento, Cláudia M Oller

    2011-06-01

    Cytokines (IL-6, IL-10, and TNF-α) are increased after exhaustive exercise in the retroperitoneal adipose tissue (RPAT) and mesenteric adipose tissue (MEAT). An exhaustive acute exercise protocol induces inflammation in adipose tissue that lasts 6 h after the exercise has ended. It is well-established that this protocol increases circulating plasma levels of non-esterified fatty acids (NEFAs) and lipopolysaccharides (LPS), compounds that are important in stimulating signaling via toll like receptor-4 (TLR-4) in different type cells. In the present study, we investigated the regulation of TLR-4 and DNA-binding of nuclear factor-κBp65 (NF-κBp65) in different depots of adipose tissue in rats after exhaustive exercise. Rats were killed by decapitation immediately (E0 group, n=6), 2 (E2 group, n=6), and 6 h (E6 group, n=6) after the exhaustive exercise, which consisted of running on a treadmill (approximately 70% V(O2max) ) for 50 min and then running at an elevated rate that increased at 1 m/min, until exhaustion. The control group (C group, n=6) was not subjected to exercise. In RPAT, TLR-4, MYD-88, and IkBα increased in the E2 group after exercise. MYD-88 and TRAF6 remained increased in the E6 group in comparison with the control group. DNA-binding of NF-κBp65 was not altered. In MEAT, TLR-4, MYD-88, TRAF6, and DNA-binding of NF-κBp65 were increased only in the E6 group. In conclusion, we have shown that increases in pro-inflammatory cytokines in adipose tissue pads after exhaustive exercise may be mediated via TLR-4 signaling, leading to increases in NF-κBp65 binding to DNA in MEAT. PMID:20945364

  1. The 3000-4000 cal. BP anthropogenic shift in fire regime in the French Pyrenees.

    NASA Astrophysics Data System (ADS)

    Rius, D.; Vannière, B.; Galop, D.; Richard, H.

    2009-04-01

    Fire is a key disturbing agent in a wide range of ecosystems: boreal biome (Pitkanen, 2000), Mediterranean area (Colombaroli et al., 2008) as well as temperate European mountain zones (Tinner et al., 1999). During the Holocene, climate may control fire regime by both ignition and fire spread-favouring conditions (i.e. composition, structure and moisture of biomass) whereas man may change charcoal accumulation patterns through type and intensity of agro-pastoral activities. In western and Mediterranean Europe, single sites charcoal analysis recorded the anthropogenic forcing over fire regime broadly between the mid and the late-Holocene. Turner et al (2008) showed that climate and fire had been disconnected since 1700 cal. BP in Turkey. In central Swiss, Mean Fire Interval decreased by two times 2000 years ago due to increasing human impact (Stahli et al., 2006). In Italy, climate and man have had a combined influence on fire-hazard since ca 4000 cal. BP (Vannière et al., 2008). In the Pyrenees Mountains, the linkage between agro-pastoral practices and fire could be dated back to ca 4000-3000 cal. BP with a clear succession of a clearance phase (high fire frequency) followed by a quite linear trend throughout Middle Ages and Modern times corresponding to a change in fire use (Vanniere et al., 2001; Galop et al., 2002, Rius et al., in press). The quantification of fire regimes parameters such as frequency with robust methodological tools (Inferred Fire Frequency, Mean Fire Interval) is needed to understand and characterise such shifts. Here we present two sequences from the Lourdes basin (col d'Ech peat bog) and from the occidental Pyrenees (Gabarn peat bog), which cover the last 9000 years with high temporal resolution. The main goals of this study were to (1) assess control factors of fire regime throughout the lateglacial and Holocene (climate and/or man) on the local scale, (2) evidence the local/regional significance of these control factors , (3) discuss the

  2. A model for determining when an analysis contains sufficient detail to provide adequate NEPA coverage for a proposed action

    SciTech Connect

    Eccleston, C.H.

    1994-11-01

    Neither the National Environmental Policy Act (NEPA) nor its subsequent regulations provide substantive guidance for determining the Level of detail, discussion, and analysis that is sufficient to adequately cover a proposed action. Yet, decisionmakers are routinely confronted with the problem of making such determinations. Experience has shown that no two decisionmakers are Likely to completely agree on the amount of discussion that is sufficient to adequately cover a proposed action. one decisionmaker may determine that a certain Level of analysis is adequate, while another may conclude the exact opposite. Achieving a consensus within the agency and among the public can be problematic. Lacking definitive guidance, decisionmakers and critics alike may point to a universe of potential factors as the basis for defending their claim that an action is or is not adequately covered. Experience indicates that assertions are often based on ambiguous opinions that can be neither proved nor disproved. Lack of definitive guidance slows the decisionmaking process and can result in project delays. Furthermore, it can also Lead to inconsistencies in decisionmaking, inappropriate Levels of NEPA documentation, and increased risk of a project being challenged for inadequate coverage. A more systematic and less subjective approach for making such determinations is obviously needed. A paradigm for reducing the degree of subjectivity inherent in such decisions is presented in the following paper. The model is specifically designed to expedite the decisionmaking process by providing a systematic approach for making these determination. In many cases, agencies may find that using this model can reduce the analysis and size of NEPA documents.

  3. 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.

  4. Cell cycle-dependent inhibition of 53BP1 signaling by BRCA1

    PubMed Central

    Feng, Lin; Li, Nan; Li, Yujing; Wang, Jiadong; Gao, Min; Wang, Wenqi; Chen, Junjie

    2015-01-01

    DNA damage response mediator protein 53BP1 is a key regulator of non-homologous end-joining (NHEJ) repair. 53BP1 protects DNA broken ends from resection by recruiting two downstream factors, RIF1 (RAP1-interacting factor 1) and PTIP (Pax transactivation domain-interacting protein), to double-stranded breaks (DSBs) via ATM (ataxia telangiectasia mutated)-mediated 53BP1 phosphorylation, and competes with BRCA1-mediated homologous recombination (HR) repair in G1 phase. In contrast, BRCA1 antagonizes 53BP1-direct NHEJ repair in S/G2 phases. We and others have found that BRCA1 prevents the translocation of RIF1 to DSBs in S/G2 phases; however, the underlying mechanism remains unclear. Here we show that efficient ATM-dependent 53BP1 phosphorylation is restricted to the G1 phase of the cell cycle, as a consequence RIF1 and PTIP accumulation at DSB sites only occur in G1 phase. Mechanistically, both BRCT and RING domains of BRCA1 are required for the inhibition of 53BP1 phosphorylation in S and G2 phases. Thus, our findings reveal how BRCA1 antagonizes 53BP1 signaling to ensure that HR repair is the dominant repair pathway in S/G2 phases.

  5. CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin.

    PubMed

    Dambacher, Silvia; Deng, Wen; Hahn, Matthias; Sadic, Dennis; Fröhlich, Jonathan; Nuber, Alexander; Hoischen, Christian; Diekmann, Stephan; Leonhardt, Heinrich; Schotta, Gunnar

    2012-01-01

    Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. In higher eukaryotes, centromeres have no specific DNA sequence and thus, they are rather determined through epigenetic mechanisms. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. The Mis18 complex, and, in particular, its member M18BP1 was shown to be essential for both incorporation and maintenance of CENP-A. Here we show that M18BP1 displays a cell cycle-regulated association with centromeric chromatin in mouse embryonic stem cells. M18BP1 is highly enriched at centromeric regions from late anaphase through to G1 phase. An interaction screen against 16 core centromeric proteins revealed a novel interaction of M18BP1 with CENP-C. We mapped the interaction domain in M18BP1 to a central region containing a conserved SANT domain and in CENP-C to the C-terminus. Knock-down of CENP-C leads to reduced M18BP1 association and lower CENP-A levels at centromeres, suggesting that CENP-C works as an important factor for centromeric M18BP1 recruitment and thus for maintaining centromeric CENP-A. PMID:22540025

  6. CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin

    PubMed Central

    Dambacher, Silvia; Deng, Wen; Hahn, Matthias; Sadic, Dennis; Fröhlich, Jonathan; Nuber, Alexander; Hoischen, Christian; Diekmann, Stephan; Leonhardt, Heinrich; Schotta, Gunnar

    2012-01-01

    Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. In higher eukaryotes, centromeres have no specific DNA sequence and thus, they are rather determined through epigenetic mechanisms. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. The Mis18 complex, and, in particular, its member M18BP1 was shown to be essential for both incorporation and maintenance of CENP-A.   Here we show that M18BP1 displays a cell cycle-regulated association with centromeric chromatin in mouse embryonic stem cells. M18BP1 is highly enriched at centromeric regions from late anaphase through to G1 phase. An interaction screen against 16 core centromeric proteins revealed a novel interaction of M18BP1 with CENP-C. We mapped the interaction domain in M18BP1 to a central region containing a conserved SANT domain and in CENP-C to the C-terminus. Knock-down of CENP-C leads to reduced M18BP1 association and lower CENP-A levels at centromeres, suggesting that CENP-C works as an important factor for centromeric M18BP1 recruitment and thus for maintaining centromeric CENP-A. PMID:22540025

  7. 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.

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

    PubMed

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

    2015-04-01

    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. PMID:25666521

  9. 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

  10. 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

  11. 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.

  12. 5-bp Classical Satellite DNA Loci from Chromosome-1 Instability in Cervical Neoplasia Detected by DNA Breakage Detection/Fluorescence in Situ Hybridization (DBD-FISH)

    PubMed Central

    Cortés-Gutiérrez, Elva I.; Ortíz-Hernández, Brenda L.; Dávila-Rodríguez, Martha I.; Cerda-Flores, Ricardo M; Fernández, José Luis; López-Fernández, Carmen; Gosálvez, Jaime

    2013-01-01

    We aimed to evaluate the association between the progressive stages of cervical neoplasia and DNA damage in 5-bp classical satellite DNA sequences from chromosome-1 in cervical epithelium and in peripheral blood lymphocytes using DNA breakage detection/fluorescence in situ hybridization (DBD-FISH). A hospital-based unmatched case-control study was conducted in 2011 with a sample of 30 women grouped according to disease stage and selected according to histological diagnosis; 10 with low-grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 with no cervical lesions, from the Unidad Medica de Alta Especialidad of The Mexican Social Security Institute, IMSS, Mexico. Specific chromosome damage levels in 5-bp classical satellite DNA sequences from chromosome-1 were evaluated in cervical epithelium and peripheral blood lymphocytes using the DBD-FISH technique. Whole-genome DNA hybridization was used as a reference for the level of damage. Results of Kruskal-Wallis test showed a significant increase according to neoplastic development in both tissues. The instability of 5-bp classical satellite DNA sequences from chromosome-1 was evidenced using chromosome-orientation FISH. In conclusion, we suggest that the progression to malignant transformation involves an increase in the instability of 5-bp classical satellite DNA sequences from chromosome-1. PMID:23429197

  13. 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

  14. 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

  15. Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells*

    PubMed Central

    Fakhraldeen, Saja A.; Clark, Rod J.; Roopra, Avtar; Chin, Emily N.; Huang, Wei; Castorino, John; Wisinski, Kari B.; Kim, TaeWon; Spiegelman, Vladimir S.; Alexander, Caroline M.

    2015-01-01

    CRD-BP/IGF2BP1 has been characterized as an “oncofetal” RNA binding protein typically highly expressed in embryonic tissues, suppressed in normal adult tissues, but induced in many tumor types. In this study, we show that adult breast tissues express ubiquitous but low levels of CRD-BP protein and mRNA. Although CRD-BP mRNA expression is induced in breast tumor cells, levels remain ∼1000-fold lower than in embryonic tissues. Despite low expression levels, CRD-BP is required for clonogenic growth of breast cancer cells. We reveal that because the most common protein isoform in normal adult breast and breast tumors has an N-terminal deletion (lacking two RNA recognition motif (RRM) domains) and is therefore missing antibody epitopes, CRD-BP expression has been under-reported by previous studies. We show that a CRD-BP mutant mouse strain retains expression of the shorter transcript (ΔN-CRD-BP), which originates in intron 2, suggesting that the impact of complete ablation of this gene in mice is not yet known. Either the full-length CRD-BP or the N-terminally truncated version can rescue the clonogenicity of CRD-BP knockdown breast cancer cells, suggesting that clonogenic function is served by either CRD-BP isoform. In summary, although CRD-BP expression levels are low in breast cancer cells, this protein is necessary for clonogenic activity. PMID:25861986

  16. Clinical and Immunological Studies of 332 Japanese Patients Tentatively Diagnosed as Anti-BP180-type Mucous Membrane Pemphigoid: A Novel BP180 C-terminal Domain Enzyme-linked Immunosorbent Assay.

    PubMed

    Yasukochi, Atsushi; Teye, Kwesi; Ishii, Norito; Hashimoto, Takashi

    2016-08-23

    Diagnosis of anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is frustrated by the difficulty of detecting BP180 reactivity. A total of 721 patients with suspected MMP, selected from a cohort of 4,698 patients with autoimmune bullous disease (AIBD), were included in this study. Of these, 332 patients were tentatively diagnosed as BP180-MMP if they showed IgG/IgA reactivity with the epidermal side of 1M NaCl-split-skin and/or positive reactivity with BP180 in at least one of our antigen detection methods. Clinically, a predominance of female patients was found. Oral mucosal and cutaneous lesions were found in 85.5% and 41.0% of patients, respectively, and frequent treatments were systemic steroids, tetracycline/minocycline and diaminodiphenyl sulfone. Various immunological methods, including a newly developed BP180 C-terminal domain enzyme-linked immunosorbent assay (ELISA), revealed frequent reactivity with BP180 C-terminal and NC16a domains. Some patients reacted with BP180 and other antigens, indicating that BP180-MMP tends to concur with other AIBDs. This large study of patients with suspected BP180-MMP indicates the difficulty of diagnosis of BP180-MMP and the diagnostic usefulness of BP180 C-terminal domain ELISA. PMID:26984589

  17. 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.

  18. Optimizing blood pressure control in hypertension: the need to use ABPM.

    PubMed

    Schmieder, Roland E; Lehmann, Marina V; Schmidt, Stephanie

    2013-04-01

    Hypertension is the most prevalent, treatable cause of cardiovascular (CV) disease. Patients with hypertension and one or more comorbidities increasingly form a significant part of the primary care practitioner's caseload. The emphasis on intensive blood pressure (BP) lowering has softened, encouraging any degree of BP lowering, since any fall in BP is beneficial for reducing CV risk. Consistency of BP control during long-term therapy (i.e. low visit-to-visit variability) and decreasing BP variability over 24-h may be as, if not more, important than degree of BP lowering per se. Fluctuations in BP between visits as well as within a 24-h period have been associated with increased CV risk. Ambulatory BP monitoring (ABPM) is a crucial element of the clinician's armamentarium not only for assessing the "true" BP load and fluctuations under real-life conditions but for identification of various abnormal BP patterns that may require attention, including white- coat hypertension, masked hypertension, non-dipping and the morning BP surge. ABPM provides accurate assessment of treatment effectiveness over 24-h and may lead to better tailoring of therapy. This article reviews the benefits of ABPM and discusses the importance of selecting long-acting antihypertensive agents for optimizing BP control. PMID:23035939

  19. 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.

  20. Identification and molecular characterization of BP75, a novel bromodomain-containing protein.

    PubMed

    Cuppen, E; van Ham, M; Pepers, B; Wieringa, B; Hendriks, W

    1999-10-15

    We here describe the identification and characterization of a novel bromodomain-containing protein, the bromodomain protein of 75 kDa (BP75). Initially, we identified BP75 in a two-hybrid screening for proteins that interact with the first PDZ (acronym for post-synaptic density protein PSD-95, Drosophila discs large tumor suppressor DlgA and the tight junction protein ZO-1) domain in protein tyrosine phosphatase-BAS-like (PTP-BL). We found that BP75 is expressed ubiquitously and show that both BP75 and a PTP-BL deletion mutant consisting of the first PDZ domain are located mainly in the nucleus, although cytoplasmic localization is also evident. Full-length PTP-BL, on the contrary, is predominantly localized in the cytoplasm, although some basal nuclear staining is observed. The described molecular interaction may reflect a mechanism of coupling submembraneous signalling events and nuclear events. PMID:10526152

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Role of the CacyBP/SIP protein in gastric cancer

    PubMed Central

    ZHAI, HUIHONG; MENG, JUAN; JIN, HAIFENG; LI, YUANFEI; WANG, JINBO

    2015-01-01

    Various reports indicate that calcyclin binding protein/Siah-1-interacting protein (CacyBP/SIP) is an important protein in tumorigenesis, but whether CacyBP/SIP promotes or suppresses cancer may depend on the cell type. In order to investigate whether CacyBP/SIP is significant in gastric cancerous tumorigenesis, the present study used immunohistochemistry to analyze 181 gastric cancer tissue samples, as well as 181 healthy tissue samples from the same gastric cancer patients. The immunohistochemical results were compared against patient data and pathological analysis of the tissue slices, including gender, age, degree of tumor differentiation and tumor, node, metastasis (TNM) stage. In addition, the level of CacyBP/SIP expression was detected in three frozen tissue samples of gastric adenocarcinoma using western blot analysis. Of the 181 cases analyzed in the present study, 80 cases were identified as non-metastatic gastric cancer and 101 cases were identified as gastric cancer that had metastasized to the lymph nodes. Tissue biopsies from the two sets of patients were examined using immunohistochemistry to identify the level of CacyBP/SIP expression in metastatic and primary gastric cancer tissues. Statistical analyses were performed on all data. The immunohistochemical analysis revealed that CacyBP/SIP was expressed in 31% (56/181) of gastric adenocarcinoma tissue samples and 7% (12/181) of adjacent non-cancerous gastric tissues (P<0.05). Furthermore, the expression levels of CacyBP/SIP were higher in cancerous tissue compared with the adjacent non-cancerous gastric tissue using western blotting. No association was identified between CacyBP/SIP expression and patient age (P=0.975), gender (P=0.185), degree of tumor differentiation (P=0.076) or TNM stage (P=0.979). Among the 101 patients with metastatic gastric cancer, CacyBP/SIP was expressed at primary sites in 31% (31/101) of cases and at metastatic sites in 26% (26/101) of cases (P=0.434). However, among the

  7. Markers of loss of control of hypertension.

    PubMed Central

    Casson, Richard Ian; King, Will D.; Godwin, Noah Marshall S.

    2003-01-01

    OBJECTIVE: To identify markers for loss of control of hypertension. DESIGN: Questionnaire administered to patients who had been monitored for 18 months and had had their blood pressure (BP) measured many times. SETTING: Fifty family practices in southeastern Ontario. PARTICIPANTS: Three hundred eighty-five adults with essential hypertension that was initially stable and controlled by medication. MAIN OUTCOME MEASURES: Change in BP (from baseline to mean of three measurements over 18 months) and proportion of patients with BP exceeding threshold values at most follow-up visits. RESULTS: Higher income was associated with an increase in diastolic BP; poor adherence to medication regimens and higher life stress were associated with increases in systolic BP Stress also led to a twofold increase in risk of exceeding BP thresholds. Other factors under study were not related to loss of control. CONCLUSION: Adherence to medication regimens, higher income, and life stress were the only factors associated with elevated BP or loss of control in previously controlled hypertension. PMID:14594101

  8. 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

  9. A novel E4BP4 element drives circadian expression of mPeriod2.

    PubMed

    Ohno, Tomoya; Onishi, Yoshiaki; Ishida, Norio

    2007-01-01

    Period2 (Per2) is an essential component of the mammalian clock mechanism and robust circadian expression of Per2 is essential for the maintenance of circadian rhythms. Although recent studies have shown that the circadian E2 enhancer (a non-canonical E-box) accounts for most of the circadian transcriptional drive of mPer2, little is known about the other cis-elements of mPer2 oscillatory transcription. Here, we examined the contribution of E4BP4 to Per2 mRNA oscillation in the cell-autonomous clock. Knockdown experiments of E4BP4 in both Northern blots and real-time luciferase assays suggested that endogenous E4BP4 negatively regulates Per2 mRNA oscillation. Sequence analysis revealed two putative E4BP4-binding sites (termed A-site and B-site) on mammalian Per2 promoter regions. Luciferase assays with mutant constructs showed that a novel E4BP4-binding site (B-site) is responsible for E4BP4-mediated transcriptional repression of Per2. Furthermore, chromatin immunoprecipitation assays in vivo showed that the peak of E4BP4 binding to the B-site on the Per2 promoter almost matched the trough of Per2 mRNA expression. Importantly, real-time luciferase assays showed that the B-site in addition to the E2 enhancer is required for robust circadian expression of Per2 in the cell-autonomous clock. These findings indicated that E4BP4 is required for the negative regulation of mammalian circadian clocks. PMID:17182630

  10. 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.

  11. Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population

    PubMed Central

    Zhang, Sheng; Tang, Weifeng; Ding, Guowen; Liu, Chao; Liu, Ruiping; Chen, Suocheng; Gu, Haiyong

    2015-01-01

    Objective To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nucleotide polymorphisms (SNPs), including TP53BP1 rs560191 G>C, CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A, and six C1orf10/CRNN variants. We performed a hospital-based case-control study to evaluate the genetic effects of these SNPs. Methods Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex SNPscanTM Kit was used to determine their genotypes. Results When the TP53BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A or the six C1orf10/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. Conclusions The results demonstrated that the functional polymorphism TP53BP1 rs560191 G>C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well-designed studies and further functional investigations are needed to confirm our findings. PMID:25937777

  12. Phentolamine as a treatment for poor mixing in transposition of the great arteries with adequate intraatrial communication.

    PubMed

    Galal, M O; El-Naggar, W I; Sharfi, M H

    2005-01-01

    Patients with transposition of the great arteries often show poor mixing for different reasons, even after adequate balloon atrial septostomy. We present a patient with such a lesion whose clinical status improved dramatically after phentolamine was applied. We believe this improvement is due to reduction in afterload caused by the alpha(2) blocker and also possibly as a response to a presumptive effect of the drug on the diastolic function of the right ventricle, allowing more left-to-right shunt across the atrial septal defect. Both phenomena can improve cardiac output in such a situation. PMID:16374695

  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. PMID:22777343

  14. Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells.

    PubMed

    Allegri, Lorenzo; Baldan, Federica; Mio, Catia; Puppin, Cinzia; Russo, Diego; Kryštof, Vladimir; Damante, Giuseppe

    2016-04-01

    Anaplastic thyroid carcinoma (ATC) is an extremely aggressive human malignancy characterized by a marked degree of invasiveness, absense of features of thyroid differentiation and resistance to current medical treatment. It is well known that ATCs are characterized by deregulation of genes related to cell cycle regulation, i.e., cyclin-dependent kinases (CDKs) and endogenous cyclin-dependent kinase inhibitors (CDKIs). Therefore, in the present study, the effect of a novel exogenous cyclin-dependent kinase inhibitor, BP-14, was investigated in three human ATC cell lines. The ATC-derived cell lines FRO, SW1736 and 8505C were treated with BP-14 alone or in combination with the mTOR inhibitor everolimus. In all ATC cell lines, treatment with BP-14 decreased cell viability and, in two of them, BP-14 modified expression of genes involved in epithelial-mesenchymal transition. Thus, our data indicate that BP-14 is a potential new compound effective against ATC. Combined treatment with BP-14 and the mTOR inhibitor everolimus had a strong synergistic effect on cell viability in all three cell lines, suggesting that the combined used of CDK and mTOR inhibitors may be a useful strategy for ATC treatment. PMID:26884249

  15. 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

  16. 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. PMID:26933806

  17. 53BP1 fosters fidelity of homology-directed DNA repair.

    PubMed

    Ochs, Fena; Somyajit, Kumar; Altmeyer, Matthias; Rask, Maj-Britt; Lukas, Jiri; Lukas, Claudia

    2016-08-01

    Repair of DNA double-strand breaks (DSBs) in mammals is coordinated by the ubiquitin-dependent accumulation of 53BP1 at DSB-flanking chromatin. Owing to its ability to limit DNA-end processing, 53BP1 is thought to promote nonhomologous end-joining (NHEJ) and to suppress homology-directed repair (HDR). Here, we show that silencing 53BP1 or exhausting its capacity to bind damaged chromatin changes limited DSB resection to hyper-resection and results in a switch from error-free gene conversion by RAD51 to mutagenic single-strand annealing by RAD52. Thus, rather than suppressing HDR, 53BP1 fosters its fidelity. These findings illuminate causes and consequences of synthetic viability acquired through 53BP1 silencing in cells lacking the BRCA1 tumor suppressor. We show that such cells survive DSB assaults at the cost of increasing reliance on RAD52-mediated HDR, which may fuel genome instability. However, our findings suggest that when challenged by DSBs, BRCA1- and 53BP1-deficient cells may become hypersensitive to, and be eliminated by, RAD52 inhibition. PMID:27348077

  18. Structural plasticity of methyllysine recognition by the tandem Tudor domain of 53BP1

    PubMed Central

    Tong, Qiong; Cui, Gaofeng; Botuyan, Maria Victoria; Rothbart, Scott B.; Hayashi, Ryo; Musselman, Catherine A.; Singh, Namit; Appella, Ettore; Strahl, Brian D.; Mer, Georges; Kutateladze, Tatiana G.

    2014-01-01

    SUMMARY p53 is dynamically regulated through various posttranslational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 co-factor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage. PMID:25579814

  19. The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2.

    PubMed

    Ohno, Tomoya; Onishi, Yoshiaki; Ishida, Norio

    2007-03-23

    The bZIP transcription factor E4BP4, is a mammalian homologue of vrille that functions as a key negative component of the circadian clock. We have shown that the E4BP4-binding site (B-site) is required in addition to a non-canonical E-box (E2 enhancer) for robust circadian Period2 (Per2) expression in the cell-autonomous clock. While the E2 enhancer and the B-site are closely situated, correlations between each component bound to the E2 enhancer and the B-site remain obscure. Here, we show that E4BP4 interacts with PER2, which represses transcriptional activity via the E-box enhancer. Interaction with PER2 required the carboxyl-terminal region that contains the repression domain of E4BP4. We also found that E4BP4 interacts with CRYPTOCHROME2 (CRY2), a key negative regulator in the mammalian circadian clock. These results suggest that E4BP4 is a component of the negative regulator complex of mammalian circadian clocks. PMID:17274955

  20. 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.