Comparison of growth, serum biochemistries and n-6 fatty acid metabolism in rats fed diets supplemented with high-gamma-linolenic acid safflower oil or borage oil for 90 days.

PubMed

Tso, Patrick; Caldwell, Jody; Lee, Dana; Boivin, Gregory P; DeMichele, Stephen J

2012-06-01

Recently, steps have been taken to further developments toward increasing gamma-linolenic acid (GLA) concentration and lowering costs in plant seed oils using transgenic technology. Through identification and expression of a fungal delta-6 desaturase gene in the high linoleic acid safflower plant, the seeds from this genetic transformation produce oil with >40% GLA (high GLA safflower oil (HGSO)). The aim of the study was to compare the effects of feeding HGSO to a generally recognized as safe source of GLA, borage oil, in a 90 day safety study in rats. Weanling male and female Sprague-Dawley rats were fed a semi-synthetic, fat free, pelleted diet (AIN93G) supplemented with a 10% (wt/wt) oil blend containing HGSO or borage oil, with equivalent GLA levels. Results demonstrated that feeding diets containing HGSO or borage oil for 90 days had similar biologic effects with regard to growth characteristics, body composition, behavior, organ weight and histology, and parameters of hematology and serum biochemistries in both sexes. Metabolism of the primary n-6 fatty acids in plasma and organ phospholipids was similar, despite minor changes in females. We conclude that HGSO is biologically equivalent to borage oil and provides a safe alternative source of GLA in the diet. Copyright © 2012 Elsevier Ltd. All rights reserved.

Self-assembled amphiphilic zein-lactoferrin micelles for tumor targeted co-delivery of rapamycin and wogonin to breast cancer.

PubMed

Sabra, Sally A; Elzoghby, Ahmed O; Sheweita, Salah A; Haroun, Medhat; Helmy, Maged W; Eldemellawy, Maha A; Xia, Ying; Goodale, David; Allan, Alison L; Rohani, Sohrab

2018-07-01

Protein-based micelles have shown significant potential for tumor-targeted delivery of anti-cancer drugs. In this light, self-assembled nanocarriers based on GRAS (Generally recognized as safe) amphiphilic protein co-polymers were synthesized via carbodiimide coupling reaction. The new nano-platform is composed of the following key components: (i) hydrophobic zein core to encapsulate the hydrophobic drugs rapamycin (RAP) and wogonin (WOG) with high encapsulation efficiency, (ii) hydrophilic lactoferrin (Lf) corona to enhance the tumor targeting, and prolong systemic circulation of the nanocarriers, and (iii) glutaraldehyde (GLA)-crosslinking to reduce the particle size and improve micellar stability. Zein-Lf micelles showed relatively rapid release of WOG followed by slower diffusion of RAP from zein core. This sequential release may aid in efflux pump inhibition by WOG thus sensitizing tumor cells to RAP action. Interestingly, these micelles showed good hemocompatibility as well as enhanced serum stability owing to the brush-like architecture of Lf shell. Moreover, this combined nano-delivery system maximized synergistic cytotoxicity of RAP and WOG in terms of tumor inhibition in MCF-7 breast cancer cells and Ehrlich ascites tumor animal model as a result of enhanced active targeting. Collectively, GLA-crosslinked zein-Lf micelles hold great promise for combined RAP/WOG delivery to breast cancer with reduced drug dose, minimized side effects and maximized anti-tumor efficacy. Copyright © 2018. Published by Elsevier B.V.

New Insulin Glargine 300 U/mL for the Treatment of Type 1 and Type 2 Diabetes Mellitus.

PubMed

Goldman, Jennifer; White, John R

2015-10-01

To describe the studies evaluating the efficacy and safety of new insulin glargine 300 U/mL (Gla-300) as a basal insulin in the treatment of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. A literature search of MEDLINE was conducted (January 2008-June 2015) using the terms U300, Gla-300, and insulin glargine 300 units/mL and supplemented with congress abstracts published in 2014 and 2015. All English language studies assessing the efficacy and/or safety of Gla-300 were evaluated. The efficacy and safety of once-daily Gla-300 has been compared with insulin glargine 100 U/mL (Gla-100) in the EDITION trials, 6 phase-3, multinational, open-label studies in T1DM and T2DM. Across these studies, Gla-300 consistently demonstrated glycemic control comparable to Gla-100; a mean (standard error) change in glycated hemoglobin A1c of -1.02% (0.03) with both Gla-100 (n = 1235) and Gla-300 (n = 1239) was seen in a patient-level meta-analysis. Gla-300 was associated with comparable or reduced nocturnal hypoglycemia compared with Gla-100; the relative risk for nocturnal hypoglycemia with Gla-300 versus Gla-100 was 0.75 (95% CI = 0.68 to 0.83) in a patient-level meta-analysis. There is also some evidence for less weight gain with Gla-300 compared with Gla-100, despite a higher insulin dose. Gla-300 was well tolerated, with the number of adverse events being comparable to that with Gla-100. These results suggest that Gla-300 may have a place as an alternative, long-acting basal insulin for patients with T1DM or T2DM, with the possibility for improved tolerability. © The Author(s) 2015.

From bed topography to ice thickness: GlaRe, a GIS tool to reconstruct the surface of palaeoglaciers

NASA Astrophysics Data System (ADS)

Pellitero, Ramon; Rea, Brice; Spagnolo, Matteo; Bakke, Jostein; Ivy-Ochs, Susan; Frew, Craig; Hughes, Philip; Ribolini, Adriano; Renssen, Hans; Lukas, Sven

2016-04-01

We present GlaRe, A GIS tool that automatically reconstructs the 3D geometry for palaeoglaciers given the bed topography. This tool utilises a numerical approach and can work using a minimum of morphological evidence i.e. the position of the palaeoglacier front. The numerical approach is based on an iterative solution to the perfect plasticity assumption for ice rheology, explained in Benn and Hulton (2010). The tool can be run in ArcGIS 10.1 (ArcInfo license) and later updates and the toolset is written in Python code. The GlaRe toolbox presented in this paper implements a well-established approach for the determination of palaeoglacier equilibrium profiles. Significantly it permits users to quickly run multiple glacier reconstructions which were previously very laborious and time consuming (typically days for a single valley glacier). The implementation of GlaRe will facilitate the reconstruction of large numbers of palaeoglaciers which will provide opportunities for such research addressing at least two fundamental problems: 1. Investigation of the dynamics of palaeoglaciers. Glacier reconstructions are often based on a rigorous interpretation of glacial landforms but not always sufficient attention and/or time has been given to the actual reconstruction of the glacier surface, which is crucial for the calculation of palaeoglacier ELAs and subsequent derivation of quantitative palaeoclimatic data. 2. the ability to run large numbers of reconstructions and over much larger spatial areas provides an opportunity to undertake palaeoglaciers reconstructions across entire mountain, ranges, regions or even continents, allowing climatic gradients and atmospheric circulation patterns to be elucidated. The tool performance has been evaluated by comparing two extant glaciers, an icefield and a cirque/valley glacier from which the subglacial topography is known with a basic reconstruction using GlaRe. Results from the comparisons between extant glacier surfaces and modelled ones show very similar ELA values on the order of 10-20 meter error (which would account for a 0.065-0.13 K degree variation on a typical -6.5 K altitudinal gradient), and these can be improved further by increasing the number of flowlines and using F factors where needed. GlaRe is able to quickly generate robust palaeoglacier surfaces based on the very limited inputs often available from the geomorphological record.

Controlled release of glaucocalyxin - a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability.

PubMed

Yanfei, Miao; Guoguang, Chen; Lili, Ren; Pingkai, Ouyang

2017-03-01

The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA). In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control. In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged T max and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet. It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

Conversion from insulin glargine U-100 to insulin glargine U-300 or insulin degludec and the impact on dosage requirements.

PubMed

Pearson, Scott M; Trujillo, Jennifer M

2018-04-01

We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 ( n = 95) or insulin degludec ( n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1-12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19-60 interquartile range (IQR)] units at baseline to 34.5 (19-70 IQR) units after follow up ( p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different ( p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 ( p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different.

Conversion from insulin glargine U-100 to insulin glargine U-300 or insulin degludec and the impact on dosage requirements

PubMed Central

Trujillo, Jennifer M.

2018-01-01

Background: We wanted to determine whether basal insulin requirements change when patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or insulin degludec. Methods: This study involved subjects seen in the University of Colorado Health Endocrine Clinic who were transitioned from Gla-100 to either Gla-300 (n = 95) or insulin degludec (n = 39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-300 or insulin degludec prescribed after first follow-up visit within 1–12 months. Secondary outcomes included changes in glycemic control and empiric dose conversion from Gla-100 to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated changes in insulin doses, and paired t tests assessed changes in glycemic control using GraphPad statistical software. Results: Median daily basal insulin dose increased for individuals transitioned from Gla-100 to Gla-300 from 30 [19–60 interquartile range (IQR)] units at baseline to 34.5 (19–70 IQR) units after follow up (p = 0.01). For patients transitioned to insulin degludec, dose changes from baseline to follow up were not significantly different (p = 0.56). At the time of transition, the prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous dose of Gla-100 (p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments were not routinely prescribed. Conclusions: Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin requirements between visits, while basal insulin requirements for those transitioned from Gla-100 to insulin degludec were not significantly different. PMID:29619208

Green leaf allowance and dairy ewe performance grazing on tropical pasture.

PubMed

De Souza, J; Batistel, F; Ticiani, E; Sandri, E C; Pedreira, C G S; Oliveira, D E

2014-06-01

The objective of this study was to explain the influence of green leaf allowance levels on the performance of dairy ewes grazing a tropical grass. Seventy-two lactating ewes grazed Aruana guineagrass (Panicum maximum Jacq. cv. Aruana) for 80 d. The treatments were 4 daily levels of green leaf allowance (GLA) on a DM basis corresponding to 4, 7, 10, and 13 kg DM/100 kg BW, which were named low, medium-low, medium-high, and high level, respectively. The experimental design was completely randomized with 3 replications. During the experimental period, 4 grazing cycles were evaluated in a rotational stocking grazing method (4 d of grazing and 16 d of rest). There was a linear effect of GLA on forage mass, and increasing GLA resulted in increased total leaf mass, reaching an asymptotic plateau around the medium-high GLA level. The stem mass increased with increased GLA, and a pronounced increase was observed between medium-high and high GLAs. Increasing GLA increased both forage disappearance rate and postgrazing forage mass. Leaf proportion increased with GLA, peaking at the medium-high level, and the opposite occurred for stem proportions, which reduced until medium-high GLA level, followed by an increase on high GLA. Forage CP decreased linearly with GLA, and increasing GLA from low to high reduced CP content by 31%. On the other hand, NDF increased 14% and ADF increased 26%, both linearly in response to greater GLA levels. Total digestible nutrients decreased linearly by 8% when GLA increased from low to high level. Milk yield increased, peaking at medium-high GLA (1.75 kg ewe(-1) d(-1)) and decreased at high GLA level (1.40 kg ewe(-1) d(-1)). Milk composition was not affected by the GLA levels. There was a reduction in stocking rate from 72 to 43 ewes/ha when GLA increased from low to high level. Productivity (milk yield kg ha(-1) d(-1)) increased as GLA increased, peaking at medium-low level (115 kg ha(-1) d(-1)). Although this tropical grass showed the same pattern in responses to GLA levels as reported in the literature with temperate pastures, the magnitude of the process changed and the maximum response in milk yield from lactating dairy ewes grazing a tropical pasture would be achieved with higher forage allowances than in temperate pastures. Overall, Aruana guineagrass grazed by lactating dairy ewes should be managed to provide 7 to 10 GLA in kg DM/100 kg BW according to the production goals.

Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus.

PubMed

Lau, Ip Tim; Lee, Ka Fai; So, Wing Yee; Tan, Kathryn; Yeung, Vincent Tok Fai

2017-01-01

To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM). Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time-action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6-12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%-17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300. Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities.

Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension.

PubMed

Yki-Järvinen, H; Bergenstal, R M; Bolli, G B; Ziemen, M; Wardecki, M; Muehlen-Bartmer, I; Maroccia, M; Riddle, M C

2015-12-01

To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs). EDITION 2 (NCT01499095) was a randomized, 6-month, multicentre, open-label, two-arm, phase IIIa study investigating once-daily Gla-300 versus Gla-100, plus OADs (excluding sulphonylureas), with a 6-month safety extension. Similar numbers of participants in each group completed 12 months of treatment [Gla-300, 315 participants (78%); Gla-100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline -0.55 (0.06)% for Gla-300 and -0.50 (0.06)% for Gla-100; LS mean difference -0.06 [95% confidence interval (CI) -0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla-300 compared with Gla-100: rate ratio 0.63 [(95% CI 0.42-0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71-0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla-300 than Gla-100 [LS mean difference -0.7 (95% CI -1.3 to -0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla-300 and Gla-100 groups). In people with type 2 diabetes treated with Gla-300 or Gla-100, and non-sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla-300 group. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effective Combination Adjuvants Engage Both TLR and Inflammasome Pathways To Promote Potent Adaptive Immune Responses.

PubMed

Seydoux, Emilie; Liang, Hong; Dubois Cauwelaert, Natasha; Archer, Michelle; Rintala, Nicholas D; Kramer, Ryan; Carter, Darrick; Fox, Christopher B; Orr, Mark T

2018-05-16

The involvement of innate receptors that recognize pathogen- and danger-associated molecular patterns is critical to programming an effective adaptive immune response to vaccination. The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) synergizes with the squalene oil-in-water emulsion (SE) formulation to induce strong adaptive responses. Although TLR4 signaling through MyD88 and TIR domain-containing adapter inducing IFN-β are essential for GLA-SE activity, the mechanisms underlying the synergistic activity of GLA and SE are not fully understood. In this article, we demonstrate that the inflammasome activation and the subsequent release of IL-1β are central effectors of the action of GLA-SE, as infiltration of innate cells into the draining lymph nodes and production of IFN-γ are reduced in ASC -/- animals. Importantly, the early proliferation of Ag-specific CD4 + T cells was completely ablated after immunization in ASC -/- animals. Moreover, numbers of Ag-specific CD4 + T and B cells as well as production of IFN-γ, TNF-α, and IL-2 and Ab titers were considerably reduced in ASC -/- , NLRP3 -/- , and IL-1R -/- mice compared with wild-type mice and were completely ablated in TLR4 -/- animals. Also, extracellular ATP, a known trigger of the inflammasome, augments Ag-specific CD4 + T cell responses, as hydrolyzing it with apyrase diminished adaptive responses induced by GLA-SE. These data thus demonstrate that GLA-SE adjuvanticity acts through TLR4 signaling and NLRP3 inflammasome activation to promote robust Th1 and B cell responses to vaccine Ags. The findings suggest that engagement of both TLR and inflammasome activators may be a general paradigm for induction of robust CD4 T cell immunity with combination adjuvants such as GLA-SE. Copyright © 2018 by The American Association of Immunologists, Inc.

Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.

PubMed

Poeta, Marco; Pierri, Luca; Vajro, Pietro

2017-08-02

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

A review of the safety and efficacy data for insulin glargine 300 units/ml, a new formulation of insulin glargine.

PubMed

Dailey, G; Lavernia, F

2015-12-01

Insulin glargine 100 units/ml (Gla-100) has become a standard of care in diabetes treatment over the past decade, providing 24-h basal insulin coverage after once-daily subcutaneous injection for many people with diabetes, with a well-established efficacy and safety profile. New insulin glargine 300 units/ml (Gla-300) is a basal insulin that provides the same number of units as Gla-100 in a third of the volume. Compared with Gla-100, Gla-300 has shown more constant and prolonged pharmacokinetic (PK)/pharmacodynamic (PD) profiles. This review summarizes the findings from the EDITION series of clinical trials that investigated Gla-300 in individuals with type 1 and type 2 diabetes mellitus. Overall, Gla-300 has been shown to achieve similar glycaemic control with less, or similar, nocturnal hypoglycaemia compared with Gla-100, and a trend towards lower hypoglycaemia at any time of day. The EDITION series of clinical trials also provides some evidence for less weight gain with Gla-300 than with Gla-100. In addition, the PK/PD profiles of Gla-300 may allow more flexibility in the timing of doses, improving convenience; thus, Gla-300 could offer several positive features for individuals with diabetes requiring basal insulin therapy. © 2015 John Wiley & Sons Ltd.

One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension.

PubMed

Riddle, M C; Yki-Järvinen, H; Bolli, G B; Ziemen, M; Muehlen-Bartmer, I; Cissokho, S; Home, P D

2015-09-01

To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial. EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed. Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c -0.17 [95% confidence interval (CI) -0.30 to -0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89-0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75-0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent. During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between treatments. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Improving Dissolution Rate of Carbamazepine-Glutaric Acid Cocrystal Through Solubilization by Excess Coformer.

PubMed

Yamashita, Hiroyuki; Sun, Changquan Calvin

2017-12-29

The use of soluble cocrystals is a promising strategy for delivering poorly soluble drugs. However, precipitation of poorly soluble crystal form during dissolution hinders the successful tablet development of cocrystals. This work was aimed to understand the mechanisms for improving dissolution performance of a soluble cocrystals by using excess coformer. A highly soluble carbamazepine (CBZ) cocrystal with- glutaric acid (GLA) was studied. Impact of excess GLA on solubility and intrinsic dissolution rate (IDR) was assessed. Viscosity of GLA solutions was also measured. Solid form of powders and pellets was examined using powder X-ray diffractometry. IDRs of cocrystal and GLA mixtures in different ratios were measured to identify a suitable formulation for maintaining high dissolution rate of CBZ-GLA in an aqueous environment. IDR of CBZ-GLA in a pH 1.2 HCl solution was improved when GLA was present in the solution. Precipitation of CBZ·2H 2 O was eliminated when GLA concentration was ≥100 mg/mL. The improved IDR was accompanied by higher solubility of CBZ in GLA solution and increased solution viscosity. The trend in IDR profile matched well with the solubility profile normalized by solution viscosity. Mixture of cocrystal and GLA led to improved IDR in simulated intestinal fluid. The excess GLA increased the aqueous solubility of CBZ·2H 2 O and, thereby, reduced the propensity to precipitation of CBZ·2H 2 O during dissolution by lowering the degree of supersaturation. This strategy allowed development of a CBZ-GLA formulation with a significantly enhanced dissolution rate than CBZ-GLA.

Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus

PubMed Central

Lau, Ip Tim; Lee, Ka Fai; So, Wing Yee; Tan, Kathryn; Yeung, Vincent Tok Fai

2017-01-01

Objective To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM) Materials and methods Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. Results In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time–action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6–12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%–17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300. Conclusion Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities. PMID:28721081

The transcriptomic fingerprint of glucoamylase over-expression in Aspergillus niger

PubMed Central

2012-01-01

Background Filamentous fungi such as Aspergillus niger are well known for their exceptionally high capacity for secretion of proteins, organic acids, and secondary metabolites and they are therefore used in biotechnology as versatile microbial production platforms. However, system-wide insights into their metabolic and secretory capacities are sparse and rational strain improvement approaches are therefore limited. In order to gain a genome-wide view on the transcriptional regulation of the protein secretory pathway of A. niger, we investigated the transcriptome of A. niger when it was forced to overexpression the glaA gene (encoding glucoamylase, GlaA) and secrete GlaA to high level. Results An A. niger wild-type strain and a GlaA over-expressing strain, containing multiple copies of the glaA gene, were cultivated under maltose-limited chemostat conditions (specific growth rate 0.1 h-1). Elevated glaA mRNA and extracellular GlaA levels in the over-expressing strain were accompanied by elevated transcript levels from 772 genes and lowered transcript levels from 815 genes when compared to the wild-type strain. Using GO term enrichment analysis, four higher-order categories were identified in the up-regulated gene set: i) endoplasmic reticulum (ER) membrane translocation, ii) protein glycosylation, iii) vesicle transport, and iv) ion homeostasis. Among these, about 130 genes had predicted functions for the passage of proteins through the ER and those genes included target genes of the HacA transcription factor that mediates the unfolded protein response (UPR), e.g. bipA, clxA, prpA, tigA and pdiA. In order to identify those genes that are important for high-level secretion of proteins by A. niger, we compared the transcriptome of the GlaA overexpression strain of A. niger with six other relevant transcriptomes of A. niger. Overall, 40 genes were found to have either elevated (from 36 genes) or lowered (from 4 genes) transcript levels under all conditions that were examined, thus defining the core set of genes important for ensuring high protein traffic through the secretory pathway. Conclusion We have defined the A. niger genes that respond to elevated secretion of GlaA and, furthermore, we have defined a core set of genes that appear to be involved more generally in the intensified traffic of proteins through the secretory pathway of A. niger. The consistent up-regulation of a gene encoding the acetyl-coenzyme A transporter suggests a possible role for transient acetylation to ensure correct folding of secreted proteins. PMID:23237452

Global diabatic heating during FGGE SOP-1 and SOP-2

NASA Technical Reports Server (NTRS)

Chen, Tsing-Chang; Baker, Wayman E.

1986-01-01

With the increase in the observational data provided by FGGE and the use of global circulation models with full physics for the data assimilation, it is now becoming feasible to attempt to estimate globally the atmospheric diabatic heating. The thermodynamic equation in isobaric coordinates and the data generated by the FGGE III-b analysis of the Goddard Laboratory for Atmospheres (GLA) are employed to serve this purpose. The results of the present study generally agree with other previous investigations. However, some important differences are also revealed. (1) The diabatic heating obtained in the tropics in the present study is larger than that obtained elsewhere; (2) the relatively large heating over the mountainous areas shown in other studies does not appear; (3) no significant negative values of diabatic heating are found in the polar regions; and (4) unlike other studies, cooling is noted over parts of Eurasia in the summer.

Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections.

PubMed

Bergenstal, Richard M; Bailey, Timothy S; Rodbard, David; Ziemen, Monika; Guo, Hailing; Muehlen-Bartmer, Isabel; Ahmann, Andrew J

2017-04-01

The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events. The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5]; P = 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (<54 mg/dL by SMPG) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]). Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100. © 2017 by the American Diabetes Association.

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension).

PubMed

Terauchi, Y; Koyama, M; Cheng, X; Sumi, M; Riddle, M C; Bolli, G B; Hirose, T

2017-10-01

To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed. The 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA 1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00-05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study

PubMed Central

Wu, Jason HY; Lemaitre, Rozenn N; King, Irena B; Song, Xiaoling; Psaty, Bruce M; Siscovick, David S; Mozaffarian, Dariush

2014-01-01

Background While omega-6 polyunsaturated fatty acids(n-6 PUFA) have been recommended to reduce CHD, controversy remains about benefits vs. harms, including concerns over theorized pro-inflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid(LA, the major dietary PUFA), γ-linolenic acid(GLA), dihomo-γ-linolenic acid(DGLA), and arachidonic acid(AA),with total and cause-specific mortality in the Cardiovascular Health Study, a community-based US cohort. Methods and Results Among 2,792 participants(age≥65y) free of CVD at baseline, plasma phospholipid n-6 PUFAwere measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34,291 person-years of follow-up(1992–2010), 1,994 deaths occurred(678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher LA was associated with lower total mortality, with extreme-quintile HR=0.87(P-trend=0.005). Lower death was largely attributable to CVD causes, especially nonarrhythmic CHD mortality(HR=0.51, 95%CI=0.32–0.82, P-trend=0.001). Circulating GLA, DGLA, and AA were not significantly associated with total or cause-specific mortality; e.g., for AA and CHD death, the extreme-quintile HR was 0.97 (95%CI=0.70–1.34, P-trend=0.87). Evaluated semi-parametrically, LA showed graded inverse associations with total mortality(P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both. Conclusions High circulating LA, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults. PMID:25124495

Glaucocalyxin A Inhibits Platelet Activation and Thrombus Formation Preferentially via GPVI Signaling Pathway

PubMed Central

Li, Qiang; Ren, Lijie; Liu, Xiaohui; Chu, Chunjun; Ozaki, Yukio; Zhang, Jian; Zhu, Li

2013-01-01

Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA), an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01μg/ml, 0.1μg/ml) significantly inhibited platelet aggregation induced by collagen (P<0.001) and CRP (P<0.01), a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent. PMID:24386454

Sustained glycaemic control and less nocturnal hypoglycaemia with insulin glargine 300U/mL compared with glargine 100U/mL in Japanese adults with type 1 diabetes (EDITION JP 1 randomised 12-month trial including 6-month extension).

PubMed

Matsuhisa, Munehide; Koyama, Masayoshi; Cheng, Xi; Sumi, Mariko; Riddle, Matthew C; Bolli, Geremia B; Hirose, Takahisa

2016-12-01

To evaluate the efficacy and safety of insulin glargine 300U/mL (Gla-300) versus glargine 100U/mL (Gla-100) in adults with type 1 diabetes in Japan over 12months. EDITION JP 1 was a multicentre, randomised, open-label phase 3 study. Following a 6-month on-treatment period, participants continued to receive Gla-300 or Gla-100 once daily, plus mealtime insulin, over a 6-month open-label extension phase. HbA1c, hypoglycaemia, body weight and adverse events were assessed. Overall, 114/122 (93%) and 114/121 (94%) of participants in the Gla-300 and Gla-100 group, respectively, completed the 6-month extension phase. Glycaemic control was sustained in both groups up to month 12 (mean HbA1c: Gla-300, 7.9% [62mmol/mol]; Gla-100, 7.8% [62mmol/mol]). Annualised rates of hypoglycaemia were lower with Gla-300 versus Gla-100; significantly for nocturnal confirmed (<3.0mmol/L [<54mg/dL]) or severe hypoglycaemia (2.39 and 3.85 events per participant-year; rate ratio: 0.62 [0.39-0.97]). No between-treatment differences in mean body weight change or adverse events were observed. Over 12months' treatment, participants with type 1 diabetes receiving Gla-300 achieved sustained glycaemic control and experienced less nocturnal hypoglycaemia that was confirmed (<3.0mmol/L [<54mg/dL]) or severe compared with Gla-100, supporting the 6-month results. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

INSULIN GLARGINE 300 U/ML IS ASSOCIATED WITH LESS WEIGHT GAIN WHILE MAINTAINING GLYCEMIC CONTROL AND LOW RISK OF HYPOGLYCEMIA COMPARED WITH INSULIN GLARGINE 100 U/ML IN AN AGING POPULATION WITH TYPE 2 DIABETES.

PubMed

Munshi, Medha N; Gill, Jasvinder; Chao, Jason; Nikonova, Elena V; Patel, Meenakshi

2018-02-01

Assess efficacy, hypoglycemia, and weight gain in patients with type 2 diabetes (T2D) treated with insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) across different age groups. Pooled data were generated for patients randomized to Gla-300 or Gla-100 in the EDITION 2 (NCT01499095) and 3 (NCT01676220) studies. In 4 age groups (<55, ≥55 to <60, ≥60 to <65, ≥65 years), glycated hemoglobin A1C (A1C), percentage of patients reaching A1C <7.5% (58 mmol/mol), weight change, confirmed hypoglycemia (blood glucose ≤70 mg/dL), and/or severe hypoglycemia (events requiring third-party assistance) were analyzed with descriptive statistics and logistic, binomial, and analysis of covariance regression modeling. A1C reductions from baseline and proportions of patients at target were similar for Gla-300 and Gla-100 across all age groups at 6 and 12 months, but hypoglycemia incidence and event rate were lower with Gla-300 at 6 (both P<.001) and 12 months ( P<.001 and P = .005, respectively). Patients on Gla-300 gained less weight than those on Gla-100 at 6 ( P = .027) and 12 months ( P = .021). Changes in weight and daily weight-adjusted insulin dose decreased with increasing age at 6 ( P<.001 and P = .017, respectively) and 12 months ( P<.001 and P = .011, respectively). Older patients with T2D may benefit from treatment with Gla-300, which is associated with a lower hypoglycemia rate and less weight gain with similar efficacy compared with Gla-100. A1C = glycated hemoglobin A1C BMI = body mass index Gla-100 = insulin glargine 100 U/mL Gla-300 = insulin glargine 300 U/mL OAD = oral antidiabetes drug T2D = type 2 diabetes.

Single-dose new insulin glargine 300 U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes.

PubMed

Shiramoto, M; Eto, T; Irie, S; Fukuzaki, A; Teichert, L; Tillner, J; Takahashi, Y; Koyama, M; Dahmen, R; Heise, T; Becker, R H A

2015-03-01

Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of new insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) in people with type 1 diabetes mellitus. In two double-blind, randomized, crossover studies, 18 Japanese participants (aged 20-65 years) and 24 European participants (aged 18-65 years) with glycated haemoglobin levels ≤9.0% (≤75 mmol/mol) received single subcutaneous doses of Gla-300, 0.4, 0.6 and 0.9 U/kg (0.9 U/kg in the European study only), and Gla-100, 0.4 U/kg. A 36-h euglycaemic clamp procedure was performed after each dosing. The serum insulin glargine concentration (INS) and glucose infusion rate (GIR) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100. In support of this, the times to 50% of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period, indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose. Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300. Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100, maintaining blood glucose control for up to 36 h in euglycaemic clamp settings in Japanese and European participants with type 1 diabetes. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Glycaemic control, hypoglycaemia, and weight change with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Japanese adults with type 2 diabetes: a 12-month comparison by concomitant sulphonylurea and/or glinide use.

PubMed

Terauchi, Yasuo; Riddle, Matthew C; Hirose, Takahisa; Koyama, Masayoshi; Cheng, Xi; Takahashi, Yoshinori; Bolli, Geremia B

2018-06-11

To explore if clinical effects and hypoglycaemia risks associated with insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) differed by sulphonylurea and/or glinide (SU/G) treatment. This was a post hoc subgroup analysis of 12-month treatment data from EDITION JP 2 (randomised, open-label, phase 3 study of Japanese people with type 2 diabetes [T2DM] receiving once-daily Gla-300/Gla-100+oral antihyperglycaemic drugs). Participants previously receiving SU/G (+SU/G) were compared with those not taking SU/G (-SU/G). Endpoints included HbA 1c , hypoglycaemia and body weight. For +SU/G (n=152, 63%), HbA 1c was reduced from baseline to month 12 for Gla-300 (8.1 % to 7.6 %) and Gla-100 (8.2 % to 7.8 %). For -SU/G (n=89, 37%), reductions were 7.8 % to 7.4 %, and 7.9 % to 7.5 % for Gla-300 and Gla-100, respectively. A lower annualised rate of hypoglycaemia with Gla-300 versus Gla-100 was observed at night (00:00-05:59 h; p=0.0001) and any time of day (24 h; p=0.0015). Irrespective of the insulin used, the incidence and rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia appeared higher in +SU/G versus -SU/G; overall, a reduced incidence of nocturnal hypoglycaemia, and rate of hypoglycaemia at any time, was observed in -SU/G versus +SU/G. In the -SU/G subgroup, weight gain differences were observed between Gla-300 and Gla-100 (p<0.0001). Participants with prior and continued SU/G use had similar therapeutic responses with basal insulin but greater risk of hypoglycaemia than those not using SU/G; hypoglycaemia risk was lower with Gla-300 than Gla-100 in both subgroups. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Improved γ-linolenic acid production in Mucor circinelloides by homologous overexpressing of delta-12 and delta-6 desaturases.

PubMed

Zhang, Yao; Luan, Xiao; Zhang, Huaiyuan; Garre, Victoriano; Song, Yuanda; Ratledge, Colin

2017-06-21

γ-Linolenic acid (GLA) is important because of its nutritional value and medicinal applications. Although the biosynthetic pathways of some plant and microbial GLA have been deciphered, current understanding of the correlation between desaturases and GLA synthesis in oleaginous fungi is incomplete. In previous work, we found that a large amount of oleic acid (OA) had not been converted to linoleic acid (LA) or GLA in Mucor circinelloides CBS 277.49, which may be due to inadequate activities of the delta-12 or delta-6 desaturases, and thus leading to the accumulation of OA and LA. Thus, it is necessary to explore the main contributing factor during the process of GLA biosynthesis in M. circinelloides. To enhance GLA production in M. circinelloides, homologous overexpression of delta-12 and two delta-6 desaturases (named delta-6-1 and delta-6-2, respectively) were analyzed. When delta-6 desaturase were overexpressed in M. circinelloides, up to 43% GLA was produced in the total fatty acids, and the yield of GLA reached 180 mg/l, which were, respectively, 38 and 33% higher than the control strain. These findings revealed that delta-6 desaturase (especially for delta-6-1 desaturase) plays an important role in GLA synthesis by M. circinelloides. The strain overexpressing delta-6-1 desaturase may have potential application in microbial GLA production.

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

PubMed

Okajima, Fumitaka; Nakamura, Yuko; Yamaguchi, Yuji; Shuto, Yuki; Kato, Katsuhito; Sugihara, Hitoshi; Emoto, Naoya

2018-04-04

Although reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported. Forty patients with type 2 diabetes who were admitted for glycemic control with basal-bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100-120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge. In the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033). In type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100. UMIN clinical trials registry (UMIN000023360).

The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3.

PubMed

Yale, Jean-François; Pettus, Jeremy Hodson; Brito-Sanfiel, Miguel; Lavalle-Gonzalez, Fernando; Merino-Trigo, Ana; Stella, Peter; Chevalier, Soazig; Buzzetti, Raffaella

2018-01-01

To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs. A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, open-label, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use. Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups. Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use. ClinicalTrials.gov NCT01499095; NCT01676220.

Harnessing indigenous plant seed oil for the production of bio-fuel by an oleaginous fungus, Cunninghamella blakesleeana- JSK2, isolated from tropical soil.

PubMed

Sukrutha, S K; Janakiraman, Savitha

2014-01-01

Cunninghamella blakesleeana- JSK2, a gamma-linolenic acid (GLA) producing tropical fungal isolate, was utilized as a tool to evaluate the influence of various plant seed oils on biomass, oleagenicity and bio-fuel production. The fungus accumulated 26 % total lipid of their dry biomass (2 g/l) and 13 % of GLA in its total fatty acid. Among the various plant seed oils tested as carbon sources for biotransformation studies, watermelon oil had an effect on biomass and total lipid increasing up to 9.24 g/l and 34 % respectively. Sunflower, pumpkin, and onion oil increased GLA content between 15-18 %. Interestingly, an indigenous biodiesel commodity, Pongamia pinnata oil showed tremendous effect on fatty acid profile in C. blakesleeana- JSK2, when used as a sole source of carbon. There was complete inhibition of GLA from 13 to 0 % and increase in oleic acid content, one of the key components of biodiesel to 70 % (from 20 % in control). Our results suggest the potential application of indigenous plant seed oils, particularly P. pinnata oil, for the production of economically valuable bio-fuel in oleaginous fungi in general, and C. blakesleeana- JSK2, in particular.

New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 1 Diabetes: A Randomized, Phase 3a, Open-Label Clinical Trial (EDITION 4).

PubMed

Home, Philip D; Bergenstal, Richard M; Bolli, Geremia B; Ziemen, Monika; Rojeski, Maria; Espinasse, Melanie; Riddle, Matthew C

2015-12-01

Insulin therapy in type 1 diabetes still provides suboptimal outcomes. Insulin glargine 300 units/mL (Gla-300), with a flatter pharmacodynamic profile compared with insulin glargine 100 units/mL (Gla-100), is an approach to this problem. People with type 1 diabetes, using a mealtime and basal insulin regimen, were randomized open-label to Gla-300 or Gla-100 and to morning or evening injection, continuing the mealtime analog, and followed for 6 months. Participants (n = 549) were a mean age of 47 years and had a mean duration of diabetes of 21 years and BMI of 27.6 kg/m(2). The change in HbA1c (primary end point; baseline 8.1%) was equivalent in the two treatment groups (difference, 0.04% [95% CI -0.10 to 0.19]) (0.4 mmol/mol [-1.1 to 2.1]), and Gla-300 was thus noninferior. Similar results with wider 95% CIs were found for morning and evening injection times and for prebreakfast self-measured plasma glucose (SMPG) overall. Results were also similar for Gla-300 when morning and evening injection time was compared, including overlapping 8-point SMPG profiles. Hypoglycemia did not differ, except for the first 8 weeks of the study, when nocturnal confirmed or severe hypoglycemia was lower with Gla-300 (rate ratio 0.69 [95% CI 0.53-0.91]). Hypoglycemia with Gla-300 did not differ by time of injection. The basal insulin dose was somewhat higher at 6 months for Gla-300. The adverse event profile did not differ and was independent of the Gla-300 time of injection. Weight gain was lower with Gla-300. In long-duration type 1 diabetes, Gla-300 provides similar glucose control to Gla-100, with a lower risk of hypoglycemia after transfer from other insulins, independent of time of injection, and less weight gain. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes.

PubMed

Ritzel, R; Roussel, R; Bolli, G B; Vinet, L; Brulle-Wohlhueter, C; Glezer, S; Yki-Järvinen, H

2015-09-01

To conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. The EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). No significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference -0.28 kg (95% CI -0.55 to -0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events. Gla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Glycaemic control and hypoglycaemia during 12 months of randomized treatment with insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 1 diabetes (EDITION 4).

PubMed

Home, Philip D; Bergenstal, Richard M; Bolli, Geremia B; Ziemen, Monika; Rojeski, Maria; Espinasse, Melanie; Riddle, Matthew C

2018-01-01

Insulin glargine 300 U/mL (Gla-300) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL (Gla-100). We have compared these insulins over 1 year in people with type 1 diabetes (T1DM). EDITION 4 was a 6-month, multicentre, randomized, open-label phase 3 study. People with T1DM who completed the 6 months continued randomized Gla-300 or Gla-100 once daily, morning or evening, for a further 6 months. Among 549 participants randomized, 444 completed the 12-month study period (Gla-300, 80%; Gla-100, 82%). Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups (difference, 0.02 [95% CI, -0.13 to 0.17]) %-units [0.2 (-1.5 to 1.9) mmol/mol]), to a mean of 7.86 %-units (62.4 mmol/mol) in both groups. For morning vs evening injection, there was no difference in HbA1c change over 12 months for Gla-100, but a significantly larger decrease in HbA1c was observed in the Gla-300 morning group than in the Gla-300 evening group (difference, -0.25 [-0.47 to -0.04] %-units [-2.7 (-5.2 to -0.4) mmol/mol]). Mean glucose from the 8-point SMPG profiles decreased from baseline, and was similar between the 2 treatment groups. Basal insulin dose was 20% higher with Gla-300 than with Gla-100, while hypoglycaemia event rates, analysed at night, over 24 hours, or according to different glycaemic thresholds, did not differ between treatment groups, regardless of injection time. Adverse event profiles did not differ between groups. In T1DM, Gla-300 provides glucose control comparable to that of Gla-100, and can be given at any time of day. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese adults with type 1 diabetes using basal and mealtime insulin: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 1).

PubMed

Matsuhisa, M; Koyama, M; Cheng, X; Takahashi, Y; Riddle, M C; Bolli, G B; Hirose, T

2016-04-01

To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes. The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight. Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups. In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Lymphatic Anomalies Registry

ClinicalTrials.gov

2018-01-23

Lymphatic Malformation; Generalized Lymphatic Anomaly (GLA); Central Conducting Lymphatic Anomaly; CLOVES Syndrome; Gorham-Stout Disease ("Disappearing Bone Disease"); Blue Rubber Bleb Nevus Syndrome; Kaposiform Lymphangiomatosis; Kaposiform Hemangioendothelioma/Tufted Angioma; Klippel-Trenaunay Syndrome; Lymphangiomatosis

The role of global cloud climatologies in validating numerical models

NASA Technical Reports Server (NTRS)

HARSHVARDHAN

1991-01-01

Reliable estimates of the components of the surface radiation budget are important in studies of ocean-atmosphere interaction, land-atmosphere interaction, ocean circulation and in the validation of radiation schemes used in climate models. The methods currently under consideration must necessarily make certain assumptions regarding both the presence of clouds and their vertical extent. Because of the uncertainties in assumed cloudiness, all these methods involve perhaps unacceptable uncertainties. Here, a theoretical framework that avoids the explicit computation of cloud fraction and the location of cloud base in estimating the surface longwave radiation is presented. Estimates of the global surface downward fluxes and the oceanic surface net upward fluxes were made for four months (April, July, October and January) in 1985 to 1986. These estimates are based on a relationship between cloud radiative forcing at the top of the atmosphere and the surface obtained from a general circulation model. The radiation code is the version used in the UCLA/GLA general circulation model (GCM). The longwave cloud radiative forcing at the top of the atmosphere as obtained from Earth Radiation Budget Experiment (ERBE) measurements is used to compute the forcing at the surface by means of the GCM-derived relationship. This, along with clear-sky fluxes from the computations, yield maps of the downward longwave fluxes and net upward longwave fluxes at the surface. The calculated results are discussed and analyzed. The results are consistent with current meteorological knowledge and explainable on the basis of previous theoretical and observational works; therefore, it can be concluded that this method is applicable as one of the ways to obtain the surface longwave radiation fields from currently available satellite data.

Pharmacokinetics and pharmacodynamics of insulin glargine 300 U/mL in the treatment of diabetes and their clinical relevance.

PubMed

Owens, David R

2016-08-01

A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults. This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up to May 2016. The clinical relevance of this new formulation will be addressed. Gla-300 was developed to produce a flatter and more prolonged PK/PD profile compared with insulin glargine 100 U/mL (Gla-100) in order to maintain effective glycemic control and reduce the risk of hypoglycemia. Compared to Gla-100, Gla-300 achieves lower and delayed peak concentrations with a PK exposure that is more stable and evenly distributed across a 24-h dosing interval. As a consequence, Gla-300 results in a consistent glucose-lowering effect with less variability over a 24-h dosing interval, which translates to a reduction in the rate of hypoglycemia (particularly nocturnal events).

New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2).

PubMed

Terauchi, Y; Koyama, M; Cheng, X; Takahashi, Y; Riddle, M C; Bolli, G B; Hirose, T

2016-04-01

To compare the efficacy and safety of insulin glargine 300 U/ml (Gla-300) with glargine 100 U/ml (Gla-100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)]. The EDITION JP 2 study (NCT01689142) was a 6-month, multicentre, open-label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m(2), mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla-300 or Gla-100, while continuing OAD(s). Basal insulin was titrated to target fasting self-monitored plasma glucose 4.4-5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change. Gla-300 was non-inferior to Gla-100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] -0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla-300 and Gla-100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla-300 versus Gla-100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between-treatment difference in weight change favoured Gla-300 [LS mean difference -1.0 (95% CI -1.5, -0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups. Japanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla-300 than with Gla-100, while glycaemic control did not differ. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Modulation expression of tumor necrosis factor α in the radiation-induced lung injury by glycyrrhizic acid.

PubMed

Refahi, Soheila; Pourissa, Masoud; Zirak, Mohammad Reza; Hadadi, GholamHassan

2015-01-01

To evaluate the ability of glycyrrhizic acid (GLA) to reduce the tumor necrosis factor α (TNF-α), release on messenger ribonucleic acid (mRNA) and protein production in the lungs using GLA in response to irradiation were studied. The animals were divided into four groups: No treatment (NT group), GLA treatment only (GLA group), irradiation only (XRT group), and GLA treatment plus irradiation (GLA/XRT group). Rats were killed at different time points. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of TNF-α in the lungs (compared with non-irradiated lungs). An enzyme-linked immunosorbant assay (ELISA) assay was used to measure the TNF-α protein level. The TNF-α mRNA expression in the lungs of the XRT rats was clearly higher at all-time points compared to the NT rats. The TNF-α mRNA expression in the lungs of the GLA/XRT rats was lower at all-time points compared to the XRT rats. Release of the TNF-α on protein level in the lungs of the XRT rats increased at all-time points compared to the NT rats. In contrast to the XRT rats, the lungs of the GLA/XRT rats revealed a reduction on TNF-α protein level at 6 h after irradiation. This study has clearly showed the immediate down-regulation of the TNF-α mRNA and protein production in the lungs using GLA in response to irradiation.

Modulation expression of tumor necrosis factor α in the radiation-induced lung injury by glycyrrhizic acid

PubMed Central

Refahi, Soheila; Pourissa, Masoud; Zirak, Mohammad Reza; Hadadi, GholamHassan

2015-01-01

To evaluate the ability of glycyrrhizic acid (GLA) to reduce the tumor necrosis factor α (TNF-α), release on messenger ribonucleic acid (mRNA) and protein production in the lungs using GLA in response to irradiation were studied. The animals were divided into four groups: No treatment (NT group), GLA treatment only (GLA group), irradiation only (XRT group), and GLA treatment plus irradiation (GLA/XRT group). Rats were killed at different time points. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of TNF-α in the lungs (compared with non-irradiated lungs). An enzyme-linked immunosorbant assay (ELISA) assay was used to measure the TNF-α protein level. The TNF-α mRNA expression in the lungs of the XRT rats was clearly higher at all-time points compared to the NT rats. The TNF-α mRNA expression in the lungs of the GLA/XRT rats was lower at all-time points compared to the XRT rats. Release of the TNF-α on protein level in the lungs of the XRT rats increased at all-time points compared to the NT rats. In contrast to the XRT rats, the lungs of the GLA/XRT rats revealed a reduction on TNF-α protein level at 6 h after irradiation. This study has clearly showed the immediate down-regulation of the TNF-α mRNA and protein production in the lungs using GLA in response to irradiation. PMID:26170556

New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2).

PubMed

Yki-Järvinen, Hannele; Bergenstal, Richard; Ziemen, Monika; Wardecki, Marek; Muehlen-Bartmer, Isabel; Boelle, Emmanuelle; Riddle, Matthew C

2014-12-01

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 units/day) plus oral antihyperglycemic drugs (OADs). EDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemic events from week 9 to month 6. Randomized participants (n = 811) had a mean (SD) HbA₁c of 8.24% (0.82) and BMI of 34.8 kg/m(2) (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was -0.57% (0.09) for Gla-300 and -0.56% (0.09) for Gla-100 (mean difference -0.01% [95% CI -0.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified. Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes.

PubMed

Ritzel, Robert; Roussel, Ronan; Giaccari, Andrea; Vora, Jiten; Brulle-Wohlhueter, Claire; Yki-Järvinen, Hannele

2018-03-01

To investigate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) over 12 months in a patient-level meta-analysis, using data from the EDITION studies in people with type 2 diabetes (T2DM). EDITION 1, 2 and 3 were multicentre, randomized, open-label, 2-arm, parallel-group, treat-to-target phase IIIa studies. Similar study designs and endpoints enabled a meta-analysis to be conducted. Reductions in glycated haemoglobin (HbA1c) were better sustained over 12 months with Gla-300 than with Gla-100 (least squares [LS] mean difference in change from baseline: -0.10 % [95% confidence interval {CI} -0.18 to -0.02] or -1.09 mmol/mol [95% CI -2.01 to -0.20]; P = .0174). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycaemia was 15% lower with Gla-300 vs Gla-100 at night (relative risk 0.85 [95% CI 0.77-0.92]) and 6% lower at any time of day (relative risk 0.94 [95% CI 0.90-0.98]). Rates of hypoglycaemia were 18% lower with Gla-300 vs Gla-100 at night (rate ratio 0.82 [95% CI 0.67-0.99]), but comparable at any time of day. HbA1c <7.0 % without nocturnal hypoglycaemia was achieved by 24% more participants with Gla-300 than with Gla-100 (relative risk 1.24 [95% CI 1.03-1.50]). Severe hypoglycaemia was rare; in both treatment groups the incidence of events at any time of day was ≤3.6%, while rates were ≤0.08 events per participant-year. In a broad population of people with T2DM over 12 months, use of Gla-300 provided more sustained glycaemic control and significantly lower hypoglycaemia risk at night and at any time of day compared with Gla-100. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Clinical and economic outcomes in patients with type 2 diabetes initiating insulin glargine disposable pen versus exenatide BID.

PubMed

Baser, Onur; Wei, Wenhui; Baser, Erdem; Xie, Lin

2011-01-01

To evaluate clinical and economic outcomes in patients with type 2 diabetes mellitus (T2DM) who failed oral anti-diabetic drug (OAD) therapy and initiated either insulin glargine with disposable pen (GLA-P) or exenatide BID (EXE). This retrospective study used data from a large US-managed care claims database and included adult T2DM patients initiating treatment with GLA-P or EXE in 2007 or 2008. Propensity score matching was used to control observed baseline differences between treatment groups. Primary study end-points included treatment persistence, A1C, healthcare utilization, and healthcare costs during the 1-year follow-up period. Two thousand three hundred and thirty nine patients were included in the study (GLA-P: 381; EXE: 1958); 626 patients were in the 1:1 matched cohort (54% male; mean age: 54 years; mean A1C: 9.2%). At follow-up, patients in the GLA-P group were significantly more persistent in treatment than EXE patients (48% vs 15% in persistence rate and 252 vs 144 days in persistence days; both p<0.001). GLA-P patients also had significantly lower A1C at follow-up (8.02% vs 8.32%; p=0.042) and greater A1C reduction from baseline (-1.23% vs -0.92%; p=0.038). There were no significant differences in claims-based hypoglycemia rates and overall diabetes-related healthcare utilization and cost. Since this was a retrospective analysis, causality of treatment benefits cannot be established. The study was specific to two treatments and may not generalize to other models of insulin administration. Some of the results, although statistically significant, may not be found clinically important. In a real-world setting among T2DM patients who failed to achieve or sustain glycemic goal with OADs, initiation of GLA-P instead of EXE may be a more effective option because it was associated with greater treatment persistence, greater A1C reduction without a significantly higher rate of hypoglycemia, and similar healthcare costs.

Therapeutically interchangeable? A study of real-world outcomes associated with switching basal insulin analogues among US patients with type 2 diabetes mellitus using electronic medical records data.

PubMed

Levin, P; Wei, W; Miao, R; Ye, F; Xie, L; Baser, O; Gill, J

2015-03-01

To evaluate real-world clinical outcomes for switching basal insulin analogues [insulin glargine (GLA) and insulin detemir (DET)] among US patients with type 2 diabetes mellitus (T2DM). Using the GE Centricity Electronic Medical Records database, this retrospective study examined two cohorts: cohort 1, comprising patients previously on GLA and then either switching to DET (DET-S) or continuing with GLA (GLA-C); and cohort 2, comprising patients previously on DET and then either switching to GLA (GLA-S) or continuing with DET (DET-C). Within each cohort, treatment groups were propensity-score-matched on baseline characteristics. At 1-year follow-up, insulin treatment patterns, glycated haemoglobin (HbA1c) levels, hypoglycaemic events, weight and body mass index (BMI) were evaluated. The analysis included 13 942 patients: cohort 1: n = 10 657 (DET-S, n = 1797 matched to GLA-C, n = 8860) and cohort 2: n = 3285 (GLA-S, n = 858 matched to DET-C, n = 2427). Baseline characteristics were similar between the treatment groups in each cohort. At 1-year follow-up, in cohort 1, patients in the DET-S subgroup were significantly less persistent with treatment, more likely to use a rapid-acting insulin analogue, had higher HbA1c values, lower HbA1c reductions and lower proportions of patients achieving HbA1c <7.0 or <8.0% compared with patients in the GLA-C subgroup, while hypoglycaemia rates and BMI/weight values and change from baseline were similar in the two subgroups. In cohort 2, overall, there were contrasting findings between patients in the GLA-S and those in the DET-C subgroup. This study showed contrasting results when patients with T2DM switched between basal insulin analogues, although these preliminary results may be subject to limitations in the analysis. Nevertheless, this study calls into question the therapeutic interchangeability of GLA and DET, and this merits further investigation. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Efficacy and Safety of Switching from Insulin Glargine 100 U/mL to the Same Dose of Glargine 300 U/mL in Japanese Type 1 and 2 Diabetes Patients: A Retrospective Analysis.

PubMed

Nakanishi, Shuhei; Iwamoto, Masahiro; Kamei, Shinji; Hirukawa, Hidenori; Shimoda, Masashi; Tatsumi, Fuminori; Kohara, Kenji; Obata, Atsushi; Kimura, Tomohiko; Kinoshita, Tomoe; Irie, Shintaro; Sanada, Junpei; Fushimi, Yoshiro; Nishioka, Momoyo; Mizoguchi, Akiko; Kameyama, Miyuki; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki

2018-01-01

Objective Insulin glargine [300 U/mL (Gla-300)] achieved better glycemic control and reduced the risk of hypoglycemia in comparison to glargine [100 U/mL; (Gla-100)] in phase 3 trials. This is the first study to retrospectively evaluate the efficacy and safety of Gla-300 in Japanese type 1 and 2 diabetes patients in a routine clinical setting. Methods We analyzed 20 type 1 diabetes patients and 62 type 2 diabetes patients who switched from Gla-100 to the same dose of Gla-300. Sixty type 2 diabetes patients who continued the use of Gla-100 during the study were included as controls. Results At three months after switching, the HbA1c levels were decreased in the patients with type 1 diabetes, but not to a significant extent. In the type 2 diabetes patients, the HbA1c levels were significantly decreased after switching (p<0.01). In contrast, there was no change in the HbA1c levels of the type 2 diabetes patients who continued the use of Gla-100 over the same period. The BMI values of the type 1 diabetes patients tended to decrease (p=0.06) and there was a significant decrease in the BMI values of the type 2 diabetes patients (p<0.05). There was no change in the BMI values of the type 2 diabetes patients who continued the use of Gla-100. The rates of hypoglycemia and adverse events did not change during the follow-up period. Conclusion In the clinical setting, switching from Gla-100 to the same dose of Gla-300 had a favorable effect on glycemic control and body weight control in Japanese type 1 and type 2 diabetes patients, without any increase in adverse events; however, a prospective study should be performed to confirm these findings.

Synthesis and characterization of modified carrageenan microparticles for the removal of pharmaceuticals from aqueous solutions.

PubMed

Nanaki, Stavroula G; Kyzas, George Z; Tzereme, Areti; Papageorgiou, M; Kostoglou, Margaritis; Bikiaris, Dimitrios N; Lambropoulou, Dimitra A

2015-03-01

In the present study, carrageenan microparticles were synthesized using spray-drying method and used as biosorbents for the removal of pharmaceutical compounds. The cross-linking reaction of iota-carrageenan (iCAR) and kappa-carrageenan (kCAR) with glutaraldehyde (GLA) at different concentrations (2.5% or 5% (w/w), mass of GLA per mass of CAR) was studied (iCAR/GLA2.5, iCAR/GLA5, kCAR/GLA2.5, kCAR/GLA5). The physicochemical properties of the novel cross-linked polymers were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Swelling studies were in accordance with the polymer properties, showing the lowest swelling degree (19%) by using the iCAR/GLA5 microparticles. The optimal kCAR/GLA5 microparticles were successfully employed for the removal of Metoprolol (MTPL) from aqueous samples. The adsorption capacity of the adsorbents was investigated using a batch adsorption procedure and the kinetics and thermodynamics of the adsorption process were further investigated. It was found that the adsorption isotherms agree well with the Langmuir-Freundlich model. The maximum adsorption capacity (Qm) was achieved in pH 6, whereas an increase of Qm was observed increasing the temperature (from 109 at 20°C to 178 mg/g at 40°C). Kinetic studies showed that the adsorption process on iCAR/GLA5 microparticles followed pseudo-second-order rate mechanism. Finally, a new phenomenological model of the adsorption process was proposed in order to extract information on the relevant sub-processes. Copyright © 2015 Elsevier B.V. All rights reserved.

rDNA insulin glargine U300 – a critical appraisal

PubMed Central

Wang, Fei; Zassman, Stefanie; Goldberg, Philip A

2016-01-01

Background As the first once-daily basal insulin analog, insulin glargine 100 U/mL (Gla-100; Lantus®) rapidly evolved into the most commonly prescribed insulin therapy worldwide. However, this insulin has clinical limitations. The approval of new basal insulin analogs in 2015 has already started to alter the prescribing landscape. Objective To review the available evidence on the clinical efficacy and safety of a more concentrated insulin glargine (recombinant DNA origin) injection 300 U/mL (Gla-300) compared to insulin Gla-100 in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). Methods The following electronic databases were searched: PubMed and MEDLINE (using Ovid platform), Scopus, BIOSIS, and Google Scholar through June 2016. Conference proceedings of the American Diabetes Association (2015–2016) were reviewed. We also manually searched reference lists of pertinent reviews and trials. Results A total of 6 pivotal Phase III randomized controlled trials known as the EDITION series were reviewed. All of these trials (n=3,500) were head-to-head comparisons evaluating the efficacy and tolerability of Gla-300 vs Gla-100 in a diverse population with T1DM and T2DM. These trials were of 6 months duration with a 6-month safety extension phase. Conclusion Gla-300 was as effective as Gla-100 for improving glycemic control over 6 months in all studies, with a lower risk of nocturnal hypoglycemia significant only in insulin-experienced patients with T2DM. Overall, patients on Gla-300 required 10%–18% more basal insulin, but with less weight gain compared with Gla-100. PMID:27980431

Functional and pharmacological evaluation of novel GLA variants in Fabry disease identifies six (two de novo) causative mutations and two amenable variants to the chaperone DGJ.

PubMed

Ferri, Lorenzo; Malesci, Duccio; Fioravanti, Antonella; Bagordo, Gaia; Filippini, Armando; Ficcadenti, Anna; Manna, Raffaele; Antuzzi, Daniela; Verrecchia, Elena; Donati, Ilaria; Mignani, Renzo; Cavicchi, Catia; Guerrini, Renzo; Morrone, Amelia

2018-06-01

Allelic heterogeneity is an important feature of the GLA gene for which almost 900 known genetic variants have been discovered so far. Pathogenetic GLA variants cause alpha-galactosidase A (α-Gal A) enzyme deficiency leading to the X-linked lysosomal storage disorder Fabry disease (FD). Benign GLA intronic and exonic variants (e.g. pseudodeficient p.Asp313Tyr) have also been described. Some GLA missense variants, previously deemed to be pathogenetic (e.g. p.Glu66Gln and p.Arg118Cys), they have been reclassified as benign after re-evaluation by functional and population studies. Hence, the functional role of novel GLA variants should be investigated to assess their clinical relevance. We identified six GLA variants in 4 males and 2 females who exhibited symptoms of FD: c.159C>G p.(Asn53Lys), c.400T>C p.(Tyr134His), c.680G>C (p.Arg227Pro), c.815A>T p.(Asn272Ile), c.907A>T p.(Ile303Phe) and c.1163_1165delTCC (p.Leu388del). We evaluated their impact on the α-Gal A protein by bioinformatic analysis and homology modelling, by analysis of the GLA mRNA, and by site-directed mutagenesis and in vitro expression studies. We also measured their responsiveness to the pharmacological chaperone DGJ. The six detected GLA variants cause deficient α-Gal A activity and impairment or loss of the protein wild-type structure. We found p.Asn53Lys and p.Ile303Phe variants to be susceptible to DGJ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Switching to insulin glargine 300 U/mL: is duration of prior basal insulin therapy important?

PubMed

Bonadonna, Riccardo C; Renard, Eric; Cheng, Alice; Fritsche, Andreas; Cali, Anna; Melas-Melt, Lydie; Umpierrez, Guillermo E

2018-04-09

To assess the impact of duration of prior basal insulin therapy on study outcomes in people with type 2 diabetes mellitus receiving insulin glargine 300 U/mL (Gla-300) or insulin glargine 100 U/mL (Gla-100) for 6 months. A post hoc patient-level meta-analysis of data from the EDITION 1 and 2 studies. Outcomes included: HbA 1c , percentage of participants with ≥1 confirmed or severe hypoglycaemic event at night (00:00-05:59 h) or any time (24 h), and body weight change. Data were analysed according to duration of prior basal insulin use: >0-≤2 years, >2-≤5 years, >5 years. This meta-analysis included 1618 participants. HbA 1c change from baseline to month 6 was comparable between Gla-300 and Gla-100 groups, regardless of duration of prior basal insulin therapy. The lower risk with Gla-300 versus Gla-100 of ≥1 confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic event, at night or any time (24 h), was unaffected by duration of prior basal insulin therapy. Similarly, weight change was unaffected by duration of prior basal insulin therapy. Switching to Gla-300 from other basal insulin therapies provided comparable glycaemic control with lower risk of hypoglycaemia versus Gla-100, regardless of duration of prior basal insulin therapy. Copyright © 2018. Published by Elsevier B.V.

Data assimilation and prognostic whole ice sheet modelling with the variationally derived, higher order, open source, and fully parallel ice sheet model VarGlaS

NASA Astrophysics Data System (ADS)

Brinkerhoff, D. J.; Johnson, J. V.

2013-07-01

We introduce a novel, higher order, finite element ice sheet model called VarGlaS (Variational Glacier Simulator), which is built on the finite element framework FEniCS. Contrary to standard procedure in ice sheet modelling, VarGlaS formulates ice sheet motion as the minimization of an energy functional, conferring advantages such as a consistent platform for making numerical approximations, a coherent relationship between motion and heat generation, and implicit boundary treatment. VarGlaS also solves the equations of enthalpy rather than temperature, avoiding the solution of a contact problem. Rather than include a lengthy model spin-up procedure, VarGlaS possesses an automated framework for model inversion. These capabilities are brought to bear on several benchmark problems in ice sheet modelling, as well as a 500 yr simulation of the Greenland ice sheet at high resolution. VarGlaS performs well in benchmarking experiments and, given a constant climate and a 100 yr relaxation period, predicts a mass evolution of the Greenland ice sheet that matches present-day observations of mass loss. VarGlaS predicts a thinning in the interior and thickening of the margins of the ice sheet.

IgG2 Antibodies against a Clinical Grade Plasmodium falciparum CSP Vaccine Antigen Associate with Protection against Transgenic Sporozoite Challenge in Mice

PubMed Central

Schwenk, Robert; Nikki, Jennifer; Rein, Lisa; Spaccapelo, Roberta; Crisanti, Andrea; Wightman, Paul D.; Ockenhouse, Christian F.; Dutta, Sheetij

2014-01-01

The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive TH1/TH2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans. PMID:25343487

New insulin glargine 300 Units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units · mL-1.

PubMed

Becker, Reinhard H A; Dahmen, Raphael; Bergmann, Karin; Lehmann, Anne; Jax, Thomas; Heise, Tim

2015-04-01

To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units · mL(-1) (Gla-300), compared with insulin glargine 100 units · mL(-1) (Gla-100) at steady state in people with type 1 diabetes. A randomized, double-blind, crossover study (N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units · kg(-1) (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units · kg(-1) Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units · kg(-1) of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h. At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼ 3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤ 105 mg · dL(-1)) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100. Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Pre- and Postnatal Exposure to Low Dose Glufosinate Ammonium Induces Autism-Like Phenotypes in Mice

PubMed Central

Laugeray, Anthony; Herzine, Ameziane; Perche, Olivier; Hébert, Betty; Aguillon-Naury, Marine; Richard, Olivier; Menuet, Arnaud; Mazaud-Guittot, Séverine; Lesné, Laurianne; Briault, Sylvain; Jegou, Bernard; Pichon, Jacques; Montécot-Dubourg, Céline; Mortaud, Stéphane

2014-01-01

Glufosinate ammonium (GLA) is one of the most widely used herbicides in agriculture. As is the case for most pesticides, potential adverse effects of GLA have not been studied from the perspective of developmental neurotoxicity. Early pesticides exposure may weaken the basic structure of the developing brain and cause permanent changes leading to a wide range of lifelong effects on health and/or behavior. Here, we addressed the developmental impact of GLA by exposing female mice to low dose GLA during both pre- and postnatal periods and analyzed potential developmental and behavioral changes of the offspring during infancy and adulthood. A neurobehavioral test battery revealed significant effects of GLA maternal exposure on early reflex development, pup communication, affiliative behaviors, and preference for social olfactory cues, but emotional reactivity and emotional memory remained unaltered. These behavioral alterations showed a striking resemblance to changes seen in animal models of Autistic Spectrum Disorders. At the brain level, GLA maternal exposure caused some increase in relative brain weight of the offspring. In addition, reduced expression of Pten and Peg3 – two genes implicated in autism-like deficits – was observed in the brain of GLA-exposed pups at postnatal day 15. Our work thus provides new data on the link between pre- and postnatal exposure to the herbicide GLA and the onset of autism-like symptoms later in life. It also raises fundamental concerns about the ability of current safety testing to assess risks of pesticide exposure during critical developmental periods. PMID:25477793

Gamma-linolenic acid ameliorated glycation-induced memory impairment in rats.

PubMed

Khan, Shahab Ali; Haider, Ali; Mahmood, Wajahat; Roome, Talat; Abbas, Ghulam

2017-12-01

γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements. The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats. GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 μM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina. Our data showed that GLA inhibited the production of AGEs (IC 50  = 1.12 ± 0.05 μM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE. The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.

Analytical Characterization of an Oil-in-Water Adjuvant Emulsion.

PubMed

Sun, Jenny; Remmele, Richard L; Sanyal, Gautam

2017-07-01

Adjuvants are typically used in subunit vaccine formulations to enhance immune responses elicited by individual antigens. Physical chemical characterization of novel adjuvants is an important step in ensuring their effective use in vaccine formulations. This paper reports application of a panel of quantitative assays developed to analyze and characterize an oil-in-water adjuvant emulsion, which contains glucopyranosyl lipid A (GLA) and is a squalene-based emulsion. GLA is a fully synthetic analogue of monophosphoryl lipid A, which is a Toll-like receptor type 4 agonist and an FDA-approved adjuvant. The GLA-stable emulsion (GLA-SE) is currently being used for a respiratory syncytial virus vaccine in a phase 2 clinical trial. GLA was quantitated using reverse-phased high-performance liquid chromatography (RP-HPLC) coupled to a mass spectrometric detector, achieving higher assay sensitivity than the charged aerosol detection routinely used. Quantitation of the excipients of GLA-SE, including squalene, egg phosphatidyl choline, and Poloxamer 188, was achieved using a simple and rapid RP-HPLC method with evaporative light scattering detection, eliminating chemical derivatization typically required for these chromophore-lacking compounds. DL-α-tocopherol, the antioxidant of the GLA-SE, was quantitated using a RP-HPLC method with conventional UV detection. The experimental results compared well with values expected for these compounds based on targeted composition of the adjuvant. The assays were applied to identify degradation of individual components in a GLA-SE sample that degraded into distinct aqueous and oil phases. The methods developed and reported here are effective tools in monitoring physicochemical integrity of the adjuvant, as well as in formulation studies.

Simultaneous enrichment of cereals with polyunsaturated fatty acids and pigments by fungal solid state fermentations.

PubMed

Čertík, Milan; Adamechová, Zuzana; Guothová, Lucia

2013-10-20

Four Mucor strains were tested for their ability to grow on four cereal substrates and enriched them with gamma-linolenic acid (GLA) and β-carotene. M. circinelloides CCF-2617 as the best producer accumulated of both GLA and β-carotene in high amounts during utilization of rye bran/spent malt grains (3:1). The first growth phase was characterized by rapid GLA biosynthesis, while distinct β-carotene formation was found in the stationary fungal growth. Therefore various cultivation conditions were tested in order to optimize the yield of either GLA or β-carotene. The fungus grown on cereal substrate supplemented with glucose produced maximal 8.5 mg β-carotene and 12.1 g GLA in 1 kg fermented substrate, respectively. On the other hand, the highest amount of GLA in the fermented substrate (24.2 g/kg) was achieved when 30% of sunflower oil was employed to the substrate. Interestingly, β-carotene biosynthesis was completely inhibited when either whey or linseed oil were added to the substrate. Copyright © 2013 Elsevier B.V. All rights reserved.

A novel restriction endonuclease GlaI for rapid and highly sensitive detection of DNA methylation coupled with isothermal exponential amplification reaction.

PubMed

Sun, Yueying; Sun, Yuanyuan; Tian, Weimin; Liu, Chenghui; Gao, Kejian; Li, Zhengping

2018-02-07

Sensitive and accurate detection of site-specific DNA methylation is of critical significance for early diagnosis of human diseases, especially cancers. Herein, for the first time we employ a novel methylation-dependent restriction endonuclease GlaI to detect site-specific DNA methylation in a highly specific and sensitive way by coupling with isothermal exponential amplification reaction (EXPAR). GlaI can only cut the methylated target site with excellent selectivity but leave the unmethylated DNA intact. Then the newly exposed end fragments of methylated DNA can trigger EXPAR for highly efficient signal amplification while the intact unmethylated DNA will not initiate EXPAR at all. As such, only the methylated DNA is quantitatively and faithfully reflected by the real-time fluorescence signal of the GlaI-EXPAR system, and the potential false positive interference from unmethylated DNA can be effectively eliminated. Therefore, by integrating the unique features of GlaI for highly specific methylation discrimination and EXPAR for rapid and powerful signal amplification, the elegant GlaI-EXPAR assay allows the direct quantification of methylated DNA with ultrahigh sensitivity and accuracy. The detection limit of methylated DNA target has been pushed down to the aM level and the whole detection process of GlaI-EXPAR can be accomplished within a short time of 2 h. More importantly, ultrahigh specificity is achieved and as low as 0.01% methylated DNA can be clearly identified in the presence of a large excess of unmethylated DNA. This GlaI-EXPAR is also demonstrated to be capable of determining site-specific DNA methylations in real genomic DNA samples. Sharing the distinct advantages of ultrahigh sensitivity, outstanding specificity and facile operation, this new GlaI-EXPAR strategy may provide a robust and reliable platform for the detection of site-specific DNA methylations with low abundances.

Identification of a Novel GLA Gene Mutation, p.Ile239Met, in Fabry Disease With a Predominant Cardiac Phenotype.

PubMed

Csányi, Beáta; Hategan, Lidia; Nagy, Viktória; Obál, Izabella; Varga, Edina T; Borbás, János; Tringer, Annamária; Eichler, Sabrina; Forster, Tamás; Rolfs, Arndt; Sepp, Róbert

2017-05-31

Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (< 0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

A study for systematic errors of the GLA forecast model in tropical regions

NASA Technical Reports Server (NTRS)

Chen, Tsing-Chang; Baker, Wayman E.; Pfaendtner, James; Corrigan, Martin

1988-01-01

From the sensitivity studies performed with the Goddard Laboratory for Atmospheres (GLA) analysis/forecast system, it was revealed that the forecast errors in the tropics affect the ability to forecast midlatitude weather in some cases. Apparently, the forecast errors occurring in the tropics can propagate to midlatitudes. Therefore, the systematic error analysis of the GLA forecast system becomes a necessary step in improving the model's forecast performance. The major effort of this study is to examine the possible impact of the hydrological-cycle forecast error on dynamical fields in the GLA forecast system.

The role of Toujeo®, insulin glargine U-300, in the treatment of diabetes mellitus.

PubMed

Brown, Meagan A; Davis, Courtney S; Fleming, Laurie W; Fleming, Joshua W

2016-09-01

The purpose of this article is to educate nurse practitioners about the role of Toujeo®, insulin glargine U-300 (Gla-300), which is a new option for the treatment of diabetes mellitus. A comprehensive literature search was conducted using MEDLINE with the key terms: insulin glargine 300, Toujeo, Gla-300, and EDITION for clinical trial data. Other resources included package inserts, drug information websites, and the World Health Organization (WHO). Gla-300 appears to be a safe and effective option for basal insulin therapy. In clinical trials, it was shown to be equally efficacious as Gla-100 with fewer episodes of hypoglycemia and slightly less weight gain, and subjects receiving Gla-300 required approximately 10 units more basal insulin to obtain the same hemoglobin A1c (HbA1c) as subjects receiving Gla-100. This new basal therapy option represents a potential advantage for patients who require higher doses of insulin because of the higher concentration of Gla-300. The lower incidence of hypoglycemia and more predictable pharmacokinetics could offer a significant therapeutic benefit in difficult-to-control patients with diabetes mellitus. The biggest disadvantage of this product is the slightly higher insulin dosage that is required to improve and/or maintain patients' HbA1c. ©2016 American Association of Nurse Practitioners.

Effects of prefermented cereal-derived substrates (ground barley and rye bran) enriched with fungal γ-linolenic acid on rumen fermentation parameters and lipid metabolism in vitro.

PubMed

Laho, T; Váradyová, Z; Mihaliková, K; Kišidayová, S; Adamechová, Z; Certík, M; Jalč, D

2011-09-01

To increase rumen output of γ-linolenic acid (GLA), we used two cereal-derived substrates, ground barley (GB) and rye bran (RB), enriched with fungal GLA as components of feed rations. We examined their effects on rumen fermentation patterns, lipid metabolism and the ciliated protozoan population in an artificial rumen. Four diets consisting of meadow hay (MH) plus unfermented (GB or RB) or prefermented (GB - TE or RB - TE) cereal-derived substrates were fermented in an artificial rumen with ovine rumen inoculum. The cereal-derived substrates were prefermented with the fungus Thamnidium elegans (TE) by fungal solid-state fermentation. The diets with TE increased the rumen input of dietary GLA (mg day(-1)) from 0 to 21 (GB - TE) or 26 (RB - TE). Both experimental diets increased the rumen output of GLA (P < 0.001). Adverse effects on the ciliate population were observed. Both diets also had an effect on the fatty acids profile. Fermentation patterns were also affected with MH + RB - TE. Cereal-derived substrates enriched with GLA effectively enhanced the output of GLA in artificial rumen. The ability of the fungal strain T. elegans to grow and utilize various agro-industrial substrates might be useful in developing potential new animal diets enriched in GLA. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

Glycolaldehyde and Ethylene Glycol on Nearly Isotropic Comets

NASA Astrophysics Data System (ADS)

Butler, Jayden; Zellner, Nicolle; McCaffrey, Vanessa

2017-01-01

The delivery of glycolaldehyde (GLA) and ethylene glycol (EG) could be could be important for understanding the origin of life. GLA, the simplest sugar, is a building block for ribose, the backbone of RNA; EG is a reduced alcohol variant of GLA, found to be created by the impact of GLA under simulated cometary impact conditions (McCaffrey et al. 2014). GLA and EG have been found in regions of the interstellar medium and recently on nearly isotropic comets (NICs), which originate in the Oort Cloud. NICs are long period comets (P > 200 years) and have orbits that are nearly randomly inclined to the ecliptic plane (Mumma & Charnley et al. 2011). Based on impact experiments that assess survivability of these molecules (McCaffrey et al. 2014), we aim to determine the mass of GLA and EG that could have been delivered on comets since the formation of the Solar System. The focus of the current study is to determine the abundances of GLA and EG on C/1995 O1 (Hale-Bopp), C/2012 F6 (Lemmon), C/2013 R1 (Lovejoy 2013), and C/2014 Q2 (Lovejoy 2014), all of which have been found to possess at least one of these molecules. Using published values of observed production rates of water, GLA, and EG (e.g., Biver et al. 2015), we have estimated a range of masses of these molecules of interest on their host comets. Even with a high degree of uncertainty in comet diameters and volumes, we estimate that 109 to 1017 kg of these molecules could be delivered by a single comet, and that 108 to 1017 kg could have survived the impact.

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis).

PubMed

Roussel, Ronan; d'Emden, Michael C; Fisher, Miles; Ampudia-Blasco, F Javier; Stella, Peter; Bizet, Florence; Cali, Anna M G; Wysham, Carol H

2018-02-01

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Physiological effects of γ-linolenic acid and sesamin on hepatic fatty acid synthesis and oxidation.

PubMed

Ide, Takashi; Iwase, Haruka; Amano, Saaya; Sunahara, Saki; Tachihara, Ayuka; Yagi, Minako; Watanabe, Tsuyoshi

2017-03-01

Interrelated effects of γ-linolenic acid (GLA) and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin) and containing 100 g/kg of palm oil (saturated fat), safflower oil rich in linoleic acid, or oil of evening primrose origin containing 43% GLA (GLA oil) for 18 days. In rats fed sesamin-free diets, GLA oil, compared with other oils, increased the activity and mRNA levels of various enzymes involved in fatty acid oxidation, except for some instances. Sesamin greatly increased these parameters, and the enhancing effects of sesamin on peroxisomal fatty acid oxidation rate and acyl-CoA oxidase, enoyl-CoA hydratase and acyl-CoA thioesterase activities were more exaggerated in rats fed GLA oil than in the animals fed other oils. The combination of sesamin and GLA oil also synergistically increased the mRNA levels of some peroxisomal fatty acid oxidation enzymes and of several enzymes involved in fatty acid metabolism located in other cell organelles. In the groups fed sesamin-free diets, GLA oil, compared with other oils, markedly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin reduced all these parameters, except for malic enzyme, in rats fed palm and safflower oils, but the effects were attenuated in the animals fed GLA oil. These changes by sesamin and fat type accompanied profound alterations in serum lipid levels. This may be ascribable to the changes in apolipoprotein-B-containing lipoproteins. Copyright © 2016 Elsevier Inc. All rights reserved.

New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1).

PubMed

Riddle, Matthew C; Bolli, Geremia B; Ziemen, Monika; Muehlen-Bartmer, Isabel; Bizet, Florence; Home, Philip D

2014-10-01

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin. EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with glycated hemoglobin A1c (HbA1c) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. Participants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m(2), and HbA1c 8.15% (65.6 mmol/mol). HbA1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P < 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified. Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Vitamin K, osteoporosis and degenerative diseases of ageing.

PubMed

Vermeer, Cees; Theuwissen, Elke

2011-03-01

The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.

Insulin glargine 300 units/mL: a guide for healthcare professionals involved in the management of diabetes.

PubMed

Strong, Jodi; Kruger, Davida; Novak, Lucia

2017-04-01

Insulin glargine 300 units/mL: Insulin glargine 300 units/mL (Gla-300) is a formulation of insulin glargine that delivers the same number of insulin units in one-third of the injectable volume of insulin glargine 100 units/mL (Gla-100). Glucose control: Recently approved in the United States and in Europe for use in type 1 and type 2 diabetes, Gla-300 has a more constant and evenly distributed glucose-lowering effect compared with Gla-100, with a duration of action beyond 24 hours and lower within-day and between-day intra-individual variability in blood glucose levels. These benefits translate into predictable and sustained glucose control from a once-daily injection, with potential for fewer hypoglycemia episodes and less weight gain. Case studies are presented to highlight the potential clinical benefits and considerations associated with initiating treatment with Gla-300 in people with type 1 and type 2 diabetes.

GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

PubMed

Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

2014-01-01

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

Survival of Glycolaldehyde and Production of Sugar Compounds via Comet Impact Delivery

NASA Astrophysics Data System (ADS)

Zellner, N.; McCaffrey, V.; Crake, C.; Butler, J.; Robbins, J.; Fodor, A.

2017-12-01

Impact experiments using glycolaldehyde (GLA), a two-carbon sugar precursor that has been detected in regions of the interstellar medium and on comets, have been conducted at the Experimental Impact Laboratory at NASA's Johnson Space Center. Samples of GLA and GLA mixed with montmorillonite clays were subjected to the pressure conditions that are found during impact delivery of biomolecules by comets, asteroids, or meteors; pressures ranged from 4.5 GPa to 25 GPa. Results show that large amounts of GLA survived the impacts and moderate amounts of threose, erythrose, and glycolic acid were produced in these impacts. Total amounts are dependent on impact pressure. Ethylene glycol, a reduced variant of GLA that has also been detected in the interstellar medium and on comets, was also produced. The results of these experimental impacts provide evidence that large amounts of GLA, EG, and other biomolecules were available on habitable moons or planets, especially during the era of late heavy bombardment ( 4.2 to 3.7 billion years ago) when life may have been developing on Earth. The presence and availability of these biomolecules, under appropriate conditions, may be important for understanding the origin of life as we know it. Glycolaldehyde in particular, may be an important molecule in the production of ribose, the five-carbon sugar in RNA.

Treatment duration (persistence) of basal insulin supported oral therapy (BOT) in Type-2 diabetic patients: comparison of insulin glargine with NPH insulin.

PubMed

Quinzler, Renate; Ude, Miriam; Franzmann, Alexandra; Feldt, Sandra; Schüssel, Katrin; Leuner, Kristina; Müller, Walter E; Dippel, Franz-Werner; Schulz, Martin

2012-01-01

To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients. This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006. A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29-1.38; unadjusted) and 1.22 (99% CI: 1.18-1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results. Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.

Efficacy and Safety of Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in High-Risk and Low-Risk Patients with Type 2 Diabetes Stratified Using Common Clinical Performance Measures.

PubMed

Lingvay, Ildiko; Chao, Jason; Dalal, Mehul R; Meneghini, Luigi F

2017-05-01

To determine whether previously reported reductions in hypoglycemia associated with insulin glargine 300 U/mL (Gla-300) compared with insulin glargine 100 U/mL (Gla-100) are impacted by patient risk category in type 2 diabetes (T2D), clinical performance measures based on the Healthcare Effectiveness Data and Information Set (HEDIS) were applied to patient-level data from the EDITION 2 and EDITION 3 clinical trials that compared Gla-300 and Gla-100. In this post hoc analysis, patients were stratified as low risk (LR) if patients were <65 years old with no comorbidities derived from HEDIS (HbA1c target <7.0% [53 mmol/mol]), or as high risk (HR) if patients were either ≥65 years old or had one or more HEDIS-defined comorbidities (HbA1c target <8.0% [64 mmol/mol]). Primary endpoint was a composite of patients achieving HbA1c target without confirmed or severe hypoglycemia over 6 months in the different treatment groups in each of the EDITION trials. There was a statistically nonsignificant trend of more patients treated with Gla-300 achieving the composite endpoint compared with Gla-100 in both the LR and HR patient cohorts, regardless of prior insulin experience. A similar trend was observed for the composite endpoint of HbA1c target without nocturnal hypoglycemia. There is a consistent, nonsignificant trend suggesting that Gla-300 might reduce the burden of hypoglycemia compared with Gla-100 in patients with T2D irrespective of whether they are classed as LR or HR based on age- and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set-derived comorbidities.

Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid composition in sciatic nerve of diabetic rats.

PubMed

Coste, T; Pierlovisi, M; Leonardi, J; Dufayet, D; Gerbi, A; Lafont, H; Vague, P; Raccah, D

1999-07-01

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid metabolism resulting from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids. Because this ubiquitous enzyme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic rats. Six groups of 10 rats were studied. Two groups served as controls supplemented with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P < 0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both in the prevention and reversal studies and partially restored Na+, K+ ATPase activity in the preventive treatment group (P < 0.0001). These effects were accompanied by a modification of phospholipid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.

A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus.

PubMed

Woo, Vincent C

2017-08-01

The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300). A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM. The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated. The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

The use of high resolution melting analysis to detect Fabry mutations in heterozygous females via dry bloodspots.

PubMed

Tai, Chang-Long; Liu, Mei-Ying; Yu, Hsiao-Chi; Chiang, Chiang-Chuan; Chiang, Hung; Suen, Jeng-Hung; Kao, Shu-Min; Huang, Yu-Hsiu; Wu, Tina Jui-Ting; Yang, Chia-Feng; Tsai, Fang-Chih; Lin, Ching-Yuang; Chang, Jan-Gowth; Chen, Hong-Duo; Niu, Dau-Ming

2012-02-18

As an X-linked genetic disorder, Fabry disease was first thought to affect males only, and females were generally considered to be asymptomatic carriers. However, recent research suggests that female carriers of Fabry disease may still develop vital organ damage causing severe morbidity and mortality. In the previous newborn screening, from 299,007 newborns, we identified a total of 20 different Fabry mutations and 121 newborns with Fabry mutations. However, we found that most female carriers are not detected by enzyme assays. A streamlined method for high resolution melting (HRM) analysis was designed to screen for GLA gene mutations using a same PCR and melting program. Primer sets were designed to cover the 7 exons and the Chinese common intronic mutation, IVS4+919G>A of GLA gene. The HRM analysis was successful in identifying heterozygous and hemizygous patients with the 20 surveyed mutations. We were also successful in using this method to test dry blood spots of newborns afflicted with Fabry mutations without having to determine DNA concentration before PCR amplification. The results of this study show that HRM could be a reliable and sensitive method for use in the rapid screening of females for GLA mutations. Copyright © 2011 Elsevier B.V. All rights reserved.

Low serum vitamin K in PXE results in defective carboxylation of mineralization inhibitors similar to the GGCX mutations in the PXE-like syndrome.

PubMed

Vanakker, Olivier M; Martin, Ludovic; Schurgers, Leon J; Quaglino, Daniela; Costrop, Laura; Vermeer, Cees; Pasquali-Ronchetti, Ivonne; Coucke, Paul J; De Paepe, Anne

2010-06-01

Soft-tissue mineralization is a tightly regulated process relying on the activity of systemic and tissue-specific inhibitors and promoters of calcium precipitation. Many of these, such as matrix gla protein (MGP) and osteocalcin (OC), need to undergo carboxylation to become active. This post-translational modification is catalyzed by the gammaglutamyl carboxylase GGCX and requires vitamin K (VK) as an essential co-factor. Recently, we described a novel phenotype characterized by aberrant mineralization of the elastic fibers resulting from mutations in GGCX. Because of the resemblance with pseudoxanthoma elasticum (PXE), a prototype disorder of elastic fiber mineralization, it was coined the PXE-like syndrome. As mutations in GGCX negatively affect protein carboxylation, it is likely that inactive inhibitors of calcification contribute to ectopic mineralization in PXE-like syndrome. Because of the remarkable similarities with PXE, we performed a comparative study of various forms of VK-dependent proteins in serum, plasma (using ELISA), and dermal tissues (using immunohistochemistry) of PXE-like and PXE patients using innovative, conformation-specific antibodies. Furthermore, we measured VK serum concentrations (using HPLC) in PXE-like and PXE samples to evaluate the VK status. In PXE-like patients, we noted an accumulation of uncarboxylated Gla proteins, MGP, and OC in plasma, serum, and in the dermis. Serum levels of VK were normal in these patients. In PXE patients, we found similar, although not identical results for the Gla proteins in the circulation and dermal tissue. However, the VK serum concentration in PXE patients was significantly decreased compared with controls. Our findings allow us to conclude that ectopic mineralization in the PXE-like syndrome and in PXE results from a deficient protein carboxylation of VK-dependent inhibitors of calcification. Although in PXE-like patients this is due to mutations in the GGCX gene, a deficiency of the carboxylation co-factor VK is at the basis of the decreased activity of calcification inhibitors in PXE.

Pulmonary immunity and durable protection induced by the ID93/GLA-SE vaccine candidate against the hyper-virulent Korean Beijing Mycobacterium tuberculosis strain K.

PubMed

Cha, Seung Bin; Kim, Woo Sik; Kim, Jong-Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Cho, Sang-Nae; Coler, Rhea N; Reed, Steven G; Shin, Sung Jae

2016-04-27

The majority of tuberculosis (TB) vaccine candidates advanced to clinical trials have been evaluated preclinically using laboratory-adapted strains. However, it has been proposed that challenge with clinical isolates in preclinical vaccine testing could provide further and more practical validation. Here, we tested the ID93/GLA-SE TB vaccine candidate against the clinical Mycobacterium tuberculosis (Mtb) strain K (Mtb K) belonging to the Beijing family, the most prevalent Mtb strain in South Korea. Mice immunized with ID93/GLA-SE exhibited a significant reduction in bacteria and reduced lung inflammation against Mtb K when compared to non-immunized controls. In addition, we analyzed the immune responses in the lungs of ID93/GLA-SE-immunized mice, and showed that ID93/GLA-SE was able to elicit sustained Th1-biased immune responses including antigen-specific multifunctional CD4(+) T cell co-producing IFN-γ, TNF-α, and IL-2 as well as a high magnitude of IFN-γ response for up to 10 weeks post-challenge. Notably, further investigation of T cell subsets in the lung following challenge showed remarkable generation of CD8(+) central memory T cells by ID93/GLA-SE-immunization. Our findings showed that ID93/GLA-SE vaccine confers a high level of robust protection against the hypervirulent Mtb Beijing infection which was characterized by pulmonary Th1-polarized T-cell immune responses. These findings may also provide relevant information for potential utility of this vaccine candidate in East-Asian countries where the Beijing genotype is highly prevalent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

PubMed

Calas, André-Guilhem; Richard, Olivier; Même, Sandra; Beloeil, Jean-Claude; Doan, Bich-Thuy; Gefflaut, Thierry; Même, William; Crusio, Wim E; Pichon, Jacques; Montécot, Céline

2008-07-01

Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

PubMed

Sirima, S B; Durier, C; Kara, L; Houard, S; Gansane, A; Loulergue, P; Bahuaud, M; Benhamouda, N; Nebié, I; Faber, B; Remarque, E; Launay, O

2017-10-27

Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. ClinicalTrials.gov NCT02014727; PACTR201402000719423. Copyright © 2017. Published by Elsevier Ltd.

Accuracy and Injection Force of the Gla-300 Injection Device Compared With Other Commercialized Disposable Insulin Pens.

PubMed

Klonoff, David; Nayberg, Irina; Thonius, Marissa; See, Florian; Abdel-Tawab, Mona; Erbstein, Frank; Haak, Thomas

2015-08-26

To deliver insulin glargine 300 U/mL (Gla-300), the widely used SoloSTAR(®) pen has been modified to allow for accurate and precise delivery of required insulin units in one-third of the volume compared with insulin glargine 100 U/mL, while improving usability. Here we compare the accuracy and injection force of 3 disposable insulin pens: Gla-300 SoloSTAR(®), FlexPen(®), and KwikPen™. For the accuracy assessment, 60 of each of the 3 tested devices were used for the delivery of 3 different doses (1 U, half-maximal dose, and maximal dose), which were measured gravimetrically. For the injection force assessment, 20 pens of each of the 3 types were tested twice at half-maximal and once at maximal dose, at an injection speed of 6 U/s. All tested pens met the International Organization for Standardization (ISO) requirements for dosing accuracy, with Gla-300 SoloSTAR showing the lowest between-dose variation (greatest reproducibility) at all dose levels. Mean injection force was significantly lower for Gla-300 SoloSTAR than for the other 2 pens at both half maximal and maximal doses (P < .0271). All tested pens were accurate according to ISO criteria, and the Gla-300 SoloSTAR pen displayed the greatest reproducibility and lowest injection force of any of the 3 tested devices. © 2015 Diabetes Technology Society.

Molecular Cloning, Characterization, and Differential Expression of a Glucoamylase Gene from the Basidiomycetous Fungus Lentinula edodes

PubMed Central

Zhao, J.; Chen, Y. H.; Kwan, H. S.

2000-01-01

The complete nucleotide sequence of putative glucoamylase gene gla1 from the basidiomycetous fungus Lentinula edodes strain L54 is reported. The coding region of the genomic glucoamylase sequence, which is preceded by eukaryotic promoter elements CAAT and TATA, spans 2,076 bp. The gla1 gene sequence codes for a putative polypeptide of 571 amino acids and is interrupted by seven introns. The open reading frame sequence of the gla1 gene shows strong homology with those of other fungal glucoamylase genes and encodes a protein with an N-terminal catalytic domain and a C-terminal starch-binding domain. The similarity between the Gla1 protein and other fungal glucoamylases is from 45 to 61%, with the region of highest conservation found in catalytic domains and starch-binding domains. We compared the kinetics of glucoamylase activity and levels of gene expression in L. edodes strain L54 grown on different carbon sources (glucose, starch, cellulose, and potato extract) and in various developmental stages (mycelium growth, primordium appearance, and fruiting body formation). Quantitative reverse transcription PCR utilizing pairs of primers specific for gla1 gene expression shows that expression of gla1 was induced by starch and increased during the process of fruiting body formation, which indicates that glucoamylases may play an important role in the morphogenesis of the basidiomycetous fungus. PMID:10831434

Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin.

PubMed

Zhou, Fang Liz; Ye, Fen; Berhanu, Paulos; Gupta, Vineet E; Gupta, Rishab A; Sung, Jennifer; Westerbacka, Jukka; Bailey, Timothy S; Blonde, Lawrence

2018-05-01

This retrospective cohort study compared real-world clinical and healthcare-resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla-300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow-up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla-300. Patients switching to Gla-300 had a significantly lower incidence of HCRU related to hypoglycaemia. All-cause and diabetes-related hospitalization and emergency-department HCRU were also favourable for Gla-300. Lower HCRU translated to lower costs in patients using Gla-300. In this real-world study, switching to Gla-300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Salivary Proteomic and microRNA Biomarkers Development for Lung Cancer Detection

DTIC Science & Technology

2013-08-01

an additional arm under an existing approved IRB at the GLA-VA titled “Salivary Biomarker Development for Oral Cancer Detection”. When we were... Oral Cancer in its title and did not include Lung Cancer. This was flagged by our administrative staff at UCLA. We informed and requested the GLA-VA to...flagging the incorrect inclusion of oral cancer in the title of the approved GLA-VA IRB. On April 3, 2013 Dr. Sheila Rowe from USAMRMC contacted us

Patient-level meta-analysis of efficacy and hypoglycaemia in people with type 2 diabetes initiating insulin glargine 100U/mL or neutral protamine Hagedorn insulin analysed according to concomitant oral antidiabetes therapy.

PubMed

Owens, David R; Traylor, Louise; Mullins, Peter; Landgraf, Wolfgang

2017-02-01

Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily. Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose. Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone. Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

FluG affects secretion in colonies of Aspergillus niger.

PubMed

Wang, Fengfeng; Krijgsheld, Pauline; Hulsman, Marc; de Bekker, Charissa; Müller, Wally H; Reinders, Marcel; de Vries, Ronald P; Wösten, Han A B

2015-01-01

Colonies of Aspergillus niger are characterized by zonal heterogeneity in growth, sporulation, gene expression and secretion. For instance, the glucoamylase gene glaA is more highly expressed at the periphery of colonies when compared to the center. As a consequence, its encoded protein GlaA is mainly secreted at the outer part of the colony. Here, multiple copies of amyR were introduced in A. niger. Most transformants over-expressing this regulatory gene of amylolytic genes still displayed heterogeneous glaA expression and GlaA secretion. However, heterogeneity was abolished in transformant UU-A001.13 by expressing glaA and secreting GlaA throughout the mycelium. Sequencing the genome of UU-A001.13 revealed that transformation had been accompanied by deletion of part of the fluG gene and disrupting its 3' end by integration of a transformation vector. Inactivation of fluG in the wild-type background of A. niger also resulted in breakdown of starch under the whole colony. Asexual development of the ∆fluG strain was not affected, unlike what was previously shown in Aspergillus nidulans. Genes encoding proteins with a signal sequence for secretion, including part of the amylolytic genes, were more often downregulated in the central zone of maltose-grown ∆fluG colonies and upregulated in the intermediate part and periphery when compared to the wild-type. Together, these data indicate that FluG of A. niger is a repressor of secretion.

Optimization of a methamphetamine conjugate vaccine for antibody production in mice.

PubMed

Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael

2016-06-01

There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. Copyright © 2016 Elsevier B.V. All rights reserved.

Divergent selection on home pen locomotor activity in a chicken model: Selection program, genetic parameters and direct response on activity and body weight

PubMed Central

2017-01-01

General locomotor activity (GLA) in poultry has attracted attention, as it negatively influences production costs (energy expenditure and feed consumption) and welfare parameters (bone strength, litter quality, feather pecking and cannibalism). Laying hen lines diverging in the average level of spontaneous locomotor activity in the home pen were developed by genetic selection using the founder New Hampshire line. Activity was recorded using RFID technology at around five weeks of age during four to five days in the home pen. After initial phenotyping, the least active birds were selected for the low activity line and the most active for the high activity line, with no gene transfer between lines. In each of six generations, approximately ten sires were mated to twenty dams producing 158 to 334 offspring per line per generation. The response to selection was rapid and of a considerable magnitude. In sixth generation, the level of GLA was approximately halved in the low and doubled in the high line compared to the control (7.2, 14.9 and 28.7 recordings/h). Estimated heritability of locomotor activity in the low and high line was 0.38 and 0.33, respectively. Males, in general, were more active than females. High line birds were significantly heavier than low line birds. In fourth, fifth, and sixth generation, low as well as high line birds were lighter than control line birds. This selection experiment demonstrates variation in heritability for GLA and, as a result, genetically diverged lines have been developed. These lines can be used as models for further studies of underlying physiological, neural and molecular genetic mechanisms of spontaneous locomotor activity. PMID:28796792

Divergent selection on home pen locomotor activity in a chicken model: Selection program, genetic parameters and direct response on activity and body weight.

PubMed

Kjaer, Joergen B

2017-01-01

General locomotor activity (GLA) in poultry has attracted attention, as it negatively influences production costs (energy expenditure and feed consumption) and welfare parameters (bone strength, litter quality, feather pecking and cannibalism). Laying hen lines diverging in the average level of spontaneous locomotor activity in the home pen were developed by genetic selection using the founder New Hampshire line. Activity was recorded using RFID technology at around five weeks of age during four to five days in the home pen. After initial phenotyping, the least active birds were selected for the low activity line and the most active for the high activity line, with no gene transfer between lines. In each of six generations, approximately ten sires were mated to twenty dams producing 158 to 334 offspring per line per generation. The response to selection was rapid and of a considerable magnitude. In sixth generation, the level of GLA was approximately halved in the low and doubled in the high line compared to the control (7.2, 14.9 and 28.7 recordings/h). Estimated heritability of locomotor activity in the low and high line was 0.38 and 0.33, respectively. Males, in general, were more active than females. High line birds were significantly heavier than low line birds. In fourth, fifth, and sixth generation, low as well as high line birds were lighter than control line birds. This selection experiment demonstrates variation in heritability for GLA and, as a result, genetically diverged lines have been developed. These lines can be used as models for further studies of underlying physiological, neural and molecular genetic mechanisms of spontaneous locomotor activity.

Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients.

PubMed

de Alencar, Dayse Oliveira; Netto, Cristina; Ashton-Prolla, Patricia; Giugliani, Roberto; Ribeiro-Dos-Santos, Ândrea; Pereira, Fernanda; Matte, Ursula; Santos, Ney; Santos, Sidney

2014-01-01

The Fabry disease is caused by mutations in the gene ( GLA ) that encodes the enzyme α-galactosidase A (α-Gal A). More than 500 pathologic variants of GLA have already been described, most of them are family-specific. In southern Brazil, a frequent single-base deletion ( GLA 30delG) was identified among four families that do not recognize any common ancestral. In order to investigate the history of this mutation (investigate the founder effect, estimate the mutation age and the most likely source), six gene-flanking microsatellite markers of the X chromosome on the mutation carriers and their parents, 150 individuals from the same population and 300 individuals that compose the Brazilian parental populations (Europeans, Africans and Native Americans) were genotyped. A common haplotype to the four families was identified and characterized as founder. The age was estimated with two statistics software (DMLE 2.2 and ESTIAGE) that agreed with 11 to 12 generations old. This result indicates that the mutation GLA 30delG was originated from a single event on the X chromosome of a European immigrant, during the southern Brazil colonization between 1710 and 1740.

The Madden-Julian Oscillation and its Impact on Northern Hemisphere Weather Predictability during Wintertime

NASA Technical Reports Server (NTRS)

Jones, Charles; Waliser, Duane E.; Lau, K. M.; Stern, W.

2003-01-01

The Madden-Julian Oscillation (MJO) is known as the dominant mode of tropical intraseasonal variability and has an important role in the coupled-atmosphere system. This study used twin numerical model experiments to investigate the influence of the MJO activity on weather predictability in the midlatitudes of the Northern Hemisphere during boreal winter. The National Aeronautics and Space Administration (NASA) Goddard laboratory for the Atmospheres (GLA) general circulation model was first used in a 10-yr simulation with fixed climatological SSTs to generate a validation data set as well as to select initial conditions for active MJO periods and Null cases. Two perturbation numerical experiments were performed for the 75 cases selected [(4 MJO phases + Null phase) _ 15 initial conditions in each]. For each alternative initial condition, the model was integrated for 90 days. Mean anomaly correlations in the midlatitudes of the Northern Hemisphere (2O deg N_60 deg.N) and standardized root-mean-square errors were computed to validate forecasts and control run. The analyses of 500-hPa geopotential height, 200-hPa Streamfunction and 850-hPa zonal wind component systematically show larger predictability during periods of active MJO as opposed to quiescent episodes of the oscillation.

A novel respiratory syncytial virus (RSV) F subunit vaccine adjuvanted with GLA-SE elicits robust protective TH1-type humoral and cellular immunity in rodent models.

PubMed

Lambert, Stacie L; Aslam, Shahin; Stillman, Elizabeth; MacPhail, Mia; Nelson, Christine; Ro, Bodrey; Sweetwood, Rosemary; Lei, Yuk Man; Woo, Jennifer C; Tang, Roderick S

2015-01-01

Illness associated with Respiratory Syncytial Virus (RSV) remains an unmet medical need in both full-term infants and older adults. The fusion glycoprotein (F) of RSV, which plays a key role in RSV infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing RSV-specific immunity. BALB/c mice and cotton rats, two well-characterized rodent models of RSV infection, were used to evaluate the immunogenicity of intramuscularly administered RSV vaccine candidates consisting of purified soluble F (sF) protein formulated with TLR4 agonist glucopyranosyl lipid A (GLA), stable emulsion (SE), GLA-SE, or alum adjuvants. Protection from RSV challenge, serum RSV neutralizing responses, and anti-F IgG responses were induced by all of the tested adjuvanted RSV sF vaccine formulations. However, only RSV sF + GLA-SE induced robust F-specific TH1-biased humoral and cellular responses. In mice, these F-specific cellular responses include both CD4 and CD8 T cells, with F-specific polyfunctional CD8 T cells that traffic to the mouse lung following RSV challenge. This RSV sF + GLA-SE vaccine formulation can also induce robust RSV neutralizing titers and prime IFNγ-producing T cell responses in Sprague Dawley rats. These studies indicate that a protein subunit vaccine consisting of RSV sF + GLA-SE can induce robust neutralizing antibody and T cell responses to RSV, enhancing viral clearance via a TH1 immune-mediated mechanism. This vaccine may benefit older populations at risk for RSV disease.

A novel mutation of α-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family.

PubMed

Ge, Wei; Wei, Bin; Zhu, Hao; Miao, Zhigang; Zhang, Weimin; Leng, Cuihua; Li, Jizhen; Zhang, Dan; Sun, Miao; Xu, Xingshun

2017-05-01

Fabry disease is an X-linked genetic disorder caused by the mutations of α-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal dominant (AD)-inherited pattern. Mutation analysis of SCN9A and GLA genes by direct sequencing and functional analysis of a novel mutation of GLA in cells were performed. Our data did not show any pathological mutations in SCN9A gene; however, a novel missense mutation c.139T>C (p.W47R) of GLA was identified in a male proband as well as two female carriers in this family. Enzyme assay of α-galactosidase A activity showed deficient enzyme activity in male patients and female carriers, further confirming the diagnosis of Fabry disease. Finally, a functional analysis indicated that the replacement of the 47th amino acid tryptophan (W47) with arginine (W47R) or glycine (W47G) led to reduced activity of α-galactosidase A in 293T cells. Therefore, these findings demonstrated that the novel mutation p.W47R of GLA is the cause of Fabry disease. Because Fabry disease and primary erythromelalgia share similar symptoms, it is a good strategy for clinical physicians to perform genetic mutation screenings on both SCN9A and GLA genes in those patients with limb burning pain but without a clear inheritant pattern.

Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.

PubMed

Meng, Lanfang; Xiu, Yan; Li, Yanli; Xu, Xiaobo; Li, Shanqun; Li, Xiao; Pak, Koon Y; Shi, Hongcheng; Cheng, Dengfeng

2015-07-01

This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Matrix Gla Protein polymorphism, but not concentrations, is associated with radiographic hand osteoarthritis

USDA-ARS?s Scientific Manuscript database

Objective. Factors associated with mineralization and osteophyte formation in osteoarthritis (OA) are incompletely understood. Genetic polymorphisms of matrix Gla protein (MGP), a mineralization inhibitor, have been associated clinically with conditions of abnormal calcification. We therefore evalua...

Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.

PubMed

Braddock, Rattana; Simán, C Martin; Hamilton, Katherine; Garland, Hugh O; Sibley, Colin P

2002-05-01

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.

Adjuvant solution for pandemic influenza vaccine production.

PubMed

Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G

2012-10-23

Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

SEM Analysis of Surface Impact on Biofilm Antibiotic Treatment.

PubMed

Gomes, Luciana Calheiros; Mergulhão, Filipe José

2017-01-01

The aim of this work was to use scanning electron microscopy (SEM) to investigate the effect of ampicillin treatment on Escherichia coli biofilms formed on two surface materials with different properties, silicone (SIL) and glass (GLA). Epifluorescence microscopy (EM) was initially used to assess biofilm formation and killing efficiency on both surfaces. This technique showed that higher bacterial colonization was obtained in the hydrophobic SIL than in the hydrophilic GLA. It has also shown that higher biofilm inactivation was attained for GLA after the antibiotic treatment (7-log reduction versus 1-log reduction for SIL). Due to its high resolution and magnification, SEM enabled a more detailed analysis of the antibiotic effect on biofilm cells, complementing the killing efficiency information obtained by EM. SEM micrographs revealed that ampicillin-treated cells have an elongated form when compared to untreated cells. Additionally, it has shown that different materials induced different levels of elongation on cells exposed to antibiotic. Biofilms formed on GLA showed a 37% higher elongation than those formed on SIL. Importantly, cell elongation was related to viability since ampicillin had a higher bactericidal effect on GLA-formed biofilms. These findings raise the possibility of using SEM for understanding the efficacy of antimicrobial treatments by observation of biofilm morphology.

The C2H2-type transcription factor, FlbC, is involved in the transcriptional regulation of Aspergillus oryzae glucoamylase and protease genes specifically expressed in solid-state culture.

PubMed

Tanaka, Mizuki; Yoshimura, Midori; Ogawa, Masahiro; Koyama, Yasuji; Shintani, Takahiro; Gomi, Katsuya

2016-07-01

Aspergillus oryzae produces a large amount of secreted proteins in solid-state culture, and some proteins such as glucoamylase (GlaB) and acid protease (PepA) are specifically produced in solid-state culture, but rarely in submerged culture. From the disruption mutant library of A. oryzae transcriptional regulators, we successfully identified a disruption mutant showing an extremely low production level of GlaB but a normal level of α-amylase production. This strain was a disruption mutant of the C2H2-type transcription factor, FlbC, which is reported to be involved in the regulation of conidiospore development. Disruption mutants of other upstream regulators comprising a conidiation regulatory network had no apparent effect on GlaB production in solid-state culture. In addition to GlaB, the production of acid protease in solid-state culture was also markedly decreased by flbC disruption. Northern blot analyses revealed that transcripts of glaB and pepA were significantly decreased in the flbC disruption strain. These results suggested that FlbC is involved in the transcriptional regulation of genes specifically expressed under solid-state cultivation conditions, possibly independent of the conidiation regulatory network.

Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-β-Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles.

PubMed

Darvishi, B; Manoochehri, S; Esfandyari-Manesh, M; Samadi, N; Amini, M; Atyabi, F; Dinarvand, R

2015-12-01

The aim of the present work was to encapsulate 18-β-Glycyrrhetinic acid (GLA) in albumin conjugated poly(lactide-co-glycolide) (PLGA) nanoparticles by a modified nanoprecipitation method. Nanoparticles (NPs) were prepared by different drug to polymer ratios, human serum albumin (HSA) content, dithiothreitol (as producer of free thiol groups) content, and acetone (as non-solvent in nanoprecipitation). NPs with a size ranging from 126 to 174 nm were achieved. The highest entrapment efficiency (89.4±4.2%) was achieved when the ratio of drug to polymer was 1:4. The zeta potential of NPs was fairly negative (-8 to -12). Fourier transform infrared spectroscopy and differential scanning calorimetry proved the conjugation of HSA to PLGA NPs. In vitro release profile of NPs showed 2 phases: an initial burst for 4 h (34-49%) followed by a slow release pattern up to the end. The antibacterial effects of NPs against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa were studied by microdilution method. The GLA-loaded NPs showed more antibacterial effect than pure GLA (2-4 times). The anticancer MTT test revealed that GLA-loaded NPs were approximately 9 times more effective than pure GLA in Hep G2 cells. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical and genetic investigation of a Japanese family with cardiac fabry disease. Identification of a novel α-galactosidase A missense mutation (G195V).

PubMed

Nakagawa, Naoki; Maruyama, Hiroki; Ishihara, Takayuki; Seino, Utako; Kawabe, Jun-ichi; Takahashi, Fumihiko; Kobayashi, Motoi; Yamauchi, Atsushi; Sasaki, Yukie; Sakamoto, Naka; Ota, Hisanobu; Tanabe, Yasuko; Takeuchi, Toshiharu; Takenaka, Toshihiro; Kikuchi, Kenjiro; Hasebe, Naoyuki

2011-01-01

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A gene (GLA), and the disease is a relatively prevalent cause of left ventricular hypertrophy mimicking idiopathic hypertrophic cardiomyopathy. We assessed clinically 5 patients of a three-generation family and also searched for GLA mutations in 10 family members. The proband had left ventricular hypertrophy with localized thinning in the basal posterior wall and late gadolinium enhancement (LGE) in the near-circumferential wall in cardiovascular magnetic resonance images and her sister had vasospastic angina pectoris without organic stenosis of the coronary arteries. LGE notably appeared in parallel with decreased α-galactosidase A activity and increased NT-pro BNP in our patients. We detected a new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution. Of the 10 family members, 5 family members each were positive and negative for this mutation. These new data extend our clinical and molecular knowledge of GLA gene mutations and confirm that a novel missense mutation in the GLA gene is important not only for a precise diagnosis of heterozygous status, but also for confirming relatives who are negative for this mutation.

Reductive amination of glutaraldehyde 2,4-dinitrophenylhydrazone using 2-picoline borane and high-performance liquid chromatographic analysis.

PubMed

Uchiyama, Shigehisa; Sakamoto, Hironari; Ohno, Akiko; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki

2012-09-21

A typical method for the measurement of glutaraldehyde (GLA) employs 2,4-dinitrophenylhydrazine (DNPH) to form GLA-DNPhydrazone derivatives. However, this method is subject to analytical errors because GLA-DNPhydrazone is a quaternary bis-derivative and forms three geometric isomers (E-E, E-Z and Z-Z) as a result of the two C[double bond, length as m-dash]N double bonds. To overcome this issue, a method for transforming the C[double bond, length as m-dash]N double bond into a C-N single bond, using reductive amination of DNPhydrazone derivatives, has been applied. The amination reaction of GLA-DNPhydrazones with 2-picoline borane is accelerated with catalytic amounts of acid and is completed within 10 minutes in the presence of 100 mmol L(-1) phosphoric acid. Reduction of GLA-DNPhydrazone by 2-picoline borane is unique and results in the formation of N-(2,4-dinitrophenyl)-1-piperidinamine (DNPPA). NMR and LC-APCI-MS data confirmed the product identification. DNPPA is very stable and did not change when stored for at least four weeks at room temperature. DNPPA has excellent solubility of 14.6 g L(-1) at 20 °C in acetonitrile. The absorption maximum wavelength and the molar absorptivity of DNPPA were 351 nm and 4.2 × 10(4) L mol(-1) cm(-1) respectively. Complete separation between the reduced forms of C1-C10 aldehyde DNPhydrazones, including DNPPA, can be achieved by operating the reversed-phase high-performance liquid chromatograph at 351 nm in gradient mode using a C18 amide column. The reductive amination method for GLA overcomes analytical errors caused by E-E, E-Z and Z-Z geometrical isomers.

A Novel Respiratory Syncytial Virus (RSV) F Subunit Vaccine Adjuvanted with GLA-SE Elicits Robust Protective TH1-Type Humoral and Cellular Immunity In Rodent Models

PubMed Central

Lambert, Stacie L.; Aslam, Shahin; Stillman, Elizabeth; MacPhail, Mia; Nelson, Christine; Ro, Bodrey; Sweetwood, Rosemary; Lei, Yuk Man; Woo, Jennifer C.; Tang, Roderick S.

2015-01-01

Background Illness associated with Respiratory Syncytial Virus (RSV) remains an unmet medical need in both full-term infants and older adults. The fusion glycoprotein (F) of RSV, which plays a key role in RSV infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing RSV-specific immunity. Methodology and Principal Findings BALB/c mice and cotton rats, two well-characterized rodent models of RSV infection, were used to evaluate the immunogenicity of intramuscularly administered RSV vaccine candidates consisting of purified soluble F (sF) protein formulated with TLR4 agonist glucopyranosyl lipid A (GLA), stable emulsion (SE), GLA-SE, or alum adjuvants. Protection from RSV challenge, serum RSV neutralizing responses, and anti-F IgG responses were induced by all of the tested adjuvanted RSV sF vaccine formulations. However, only RSV sF + GLA-SE induced robust F-specific TH1-biased humoral and cellular responses. In mice, these F-specific cellular responses include both CD4 and CD8 T cells, with F-specific polyfunctional CD8 T cells that traffic to the mouse lung following RSV challenge. This RSV sF + GLA-SE vaccine formulation can also induce robust RSV neutralizing titers and prime IFNγ-producing T cell responses in Sprague Dawley rats. Conclusions/Significance These studies indicate that a protein subunit vaccine consisting of RSV sF + GLA-SE can induce robust neutralizing antibody and T cell responses to RSV, enhancing viral clearance via a TH1 immune-mediated mechanism. This vaccine may benefit older populations at risk for RSV disease. PMID:25793508

Comparative Phosphoproteomic Analysis of the Developing Seeds in Two Indica Rice ( Oryza sativa L.) Cultivars with Different Starch Quality.

PubMed

Pang, Yuehan; Zhou, Xin; Chen, Yaling; Bao, Jinsong

2018-03-21

Protein phosphorylation plays important roles in regulation of various molecular events such as plant growth and seed development. However, its involvement in starch biosynthesis is less understood. Here, a comparative phosphoproteomic analysis of two indica rice cultivars during grain development was performed. A total of 2079 and 2434 phosphopeptides from 1273 and 1442 phosphoproteins were identified, covering 2441 and 2808 phosphosites in indica rice 9311 and Guangluai4 (GLA4), respectively. Comparative analysis identified 303 differentially phosphorylated peptides, and 120 and 258 specifically phosphorylated peptides in 9311 and GLA4, respectively. Phosphopeptides in starch biosynthesis related enzymes such as AGPase, SSIIa, SSIIIa, BEI, BEIIb, PUL, and Pho1were identified. GLA4 and 9311 had different amylose content, pasting viscosities, and gelatinization temperature, suggesting subtle difference in starch biosynthesis and regulation between GLA4 and 9311. Our study will give added impetus to further understanding the regulatory mechanism of starch biosynthesis at the phosphorylation level.

Hyper-Spectral Synthesis of Active OB Stars Using GLaDoS

NASA Astrophysics Data System (ADS)

Hill, N. R.; Townsend, R. H. D.

2016-11-01

In recent years there has been considerable interest in using graphics processing units (GPUs) to perform scientific computations that have traditionally been handled by central processing units (CPUs). However, there is one area where the scientific potential of GPUs has been overlooked - computer graphics, the task they were originally designed for. Here we introduce GLaDoS, a hyper-spectral code which leverages the graphics capabilities of GPUs to synthesize spatially and spectrally resolved images of complex stellar systems. We demonstrate how GLaDoS can be applied to calculate observables for various classes of stars including systems with inhomogenous surface temperatures and contact binaries.

Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review

PubMed Central

2011-01-01

Background Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. Methods A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur für Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP). Results A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI). Conclusions The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost-effective in 4 of 6 cost utility analyses (CUA) included. Thus insulin glargine (GLA) seems to offer good value for money. Comparability between studies is limited because of methodological and country specific aspects. The results of this review underline that evaluation of insulin therapy should use evidence on efficacy of therapy from information synthesis. The concept of relating utility decrements to fear of hypoglycaemia is a plausible approach but needs further investigation. Also future evaluations of basal-bolus insulin therapy should include costs of consumables such as needles for insulin injection as well as test strips and lancets for blood glucose self monitoring. PMID:21978524

GLA-SE, a Synthetic Toll-like Receptor 4 Agonist, Enhances T-Cell Responses to Influenza Vaccine in Older Adults

PubMed Central

Behzad, Hayedeh; Huckriede, Anke L. W.; Haynes, Laura; Gentleman, Beth; Coyle, Krysta; Wilschut, Jan C.; Kollmann, Tobias R.; Reed, Steven G.

2012-01-01

Background. The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza. Methods. The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant–stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza virus to mimic the response to natural infection following vaccination, using previously identified T-cell correlates of protection. Results. GLA-SE significantly increased the proportion of myeloid dendritic cells that produced tumor necrosis factor α, interleukin 6, and interleukin 12. When combined with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate a T-helper 1 cell response upon challenge with live influenza virus; interleukin 10 production was suppressed, thus significantly increasing the interferon γ to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza virus challenge, both of which have been shown to correlate with protection against influenza in older adults. Conclusions. Our findings suggest that a novel adjuvant, GLA-SE, combined with standard SVV has the potential to significantly improve vaccine-mediated protection against influenza in older adults. PMID:22147791

GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults.

PubMed

Behzad, Hayedeh; Huckriede, Anke L W; Haynes, Laura; Gentleman, Beth; Coyle, Krysta; Wilschut, Jan C; Kollmann, Tobias R; Reed, Steven G; McElhaney, Janet E

2012-02-01

The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza. The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza virus to mimic the response to natural infection following vaccination, using previously identified T-cell correlates of protection. GLA-SE significantly increased the proportion of myeloid dendritic cells that produced tumor necrosis factor α, interleukin 6, and interleukin 12. When combined with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate a T-helper 1 cell response upon challenge with live influenza virus; interleukin 10 production was suppressed, thus significantly increasing the interferon γ to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza virus challenge, both of which have been shown to correlate with protection against influenza in older adults. Our findings suggest that a novel adjuvant, GLA-SE, combined with standard SVV has the potential to significantly improve vaccine-mediated protection against influenza in older adults.

Cholinesterase activities and behavioral changes in Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed to glufosinate ammonium herbicide.

PubMed

Peltzer, Paola M; Junges, Celina M; Attademo, Andrés M; Bassó, Agustín; Grenón, Paula; Lajmanovich, Rafael C

2013-09-01

In this study, amphibian tadpoles of Hypsiboas pulchellus were exposed to herbicide Liberty®, which contains glufosinate ammonium (GLA), for 48 h to the following concentrations: 0 (control), 3.55, 4.74, 6.32, 8.43, 11.25, 15, 20, 26.6, and 35.5 mg GLA L(-1). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, as well as swimming capabilities (swimming speed and mean distance) were measured in tadpoles whose concentrations displayed survival rates > 85 %. Our results reveal that sublethal concentrations of GLA significantly inhibited both AChE and BChE activities in tadpoles with respect to the control, showing a concentration-dependent inhibitory effect. The highest inhibition percentages of AChE (50.86%) and BChE (53.02%) were registered in tadpoles exposed to 15 mg GLA L(-1). At this concentration, a significant increase of the swimming speed and mean distance were found in exposed tadpoles with respect to the control, as well as a negative and significant correlation between swimming speed and BChE activity, thus suggesting that this enzyme inhibition is related to an increase in swimming speed. Therefore, exposure of tadpoles to GLA in the wild at concentrations similar to those tested here may have adverse consequences at population level because neurotransmission and swimming performance are essential for tadpole performance and survival.

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group.

PubMed

Gadek, J E; DeMichele, S J; Karlstad, M D; Pacht, E R; Donahoe, M; Albertson, T E; Van Hoozen, C; Wennberg, A K; Nelson, J L; Noursalehi, M

1999-08-01

Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS. Prospective, multicentered, double-blind, randomized controlled trial. Intensive care units of five academic and teaching hospitals in the United States. We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study. Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015). The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

Vitamin K-dependent carboxylation of matrix gla protein influences the risk of calciphylaxis

USDA-ARS?s Scientific Manuscript database

Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients ...

[Serum vitamin K concentration and nutrition].

PubMed

Tsugawa, Naoko; Okano, Toshio

2007-11-01

Vitamin K (VK) is well known for its role in the synthesis of a number of blood coagulation factors. VK is also an important factor for bone metabolism via gamma-carboxylation of VK-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recently, it is rare that severe VK deficiency is observed. However, low dietary VK intake or low VK status has been shown to be associated with low bone mineral density and increased hip fracture risk. These studies suggest that there is potential VK insufficiency in bone, even in sufficient VK status for blood coagulation. In the present review, the studies concerning relationship between serum VK concentration and bone health, including pharmacokinetics of VK analogues (such as phylloquinone and menaquinone) and factors which affect on blood circulation of VK, are reviewed.

Ease of Use of the Insulin Glargine 300 U/mL Pen Injector in Insulin-Naïve People With Type 2 Diabetes.

PubMed

Pohlmeier, Harald; Berard, Lori; Brulle-Wohlhueter, Claire; Wu, Junlong; Dahmen, Raphael; Nowotny, Irene; Klonoff, David

2017-03-01

Insulin glargine 300 U/mL (Gla-300) contains the same active ingredient as glargine 100 U/mL (Gla-100), and provides the same number of units in one-third of the volume. The SoloSTAR ® injector pen has been modified to ensure accurate administration of this reduced volume and to improve user experience. Insulin- and pen-naïve adults with type 2 diabetes (T2DM) inadequately controlled with oral antihyperglycemic drugs, who had glycated hemoglobin (HbA1c) levels of 7.0-11.0 % (53-97 mmol/mol) were studied. They received once-daily Gla-300 in this 4-week, multicenter, open-label, single-arm study (NCT02227212). Ease of use/ease of learning (the primary endpoint), glycemic control, safety, and reliability of the disposable (prefilled) Gla-300 injector pen (secondary endpoints) were evaluated. At week 4, 95.0% of 40 participating subjects assessed the pen as excellent/good and none as poor/very poor; 97.5% would recommend it to others. Total Diabetes Treatment Satisfaction Questionnaire scores were stable throughout the study. Mean (SD) fasting plasma glucose levels decreased from 166.1 (35.0) mg/dL at baseline to 124.2 (41.1) mg/dL at week 4. No product technical complaints (PTCs) or adverse events (AEs) related to PTCs were reported. The number of subjects experiencing hypoglycemic events of any kind and the incidence of AEs were low. No serious AEs were reported. The Gla-300 injector pen is easy to use and easy to learn to use, with demonstrable reliability and high degrees of acceptance and treatment satisfaction. Once-daily Gla-300 basal insulin treatment was well tolerated and effective in pen- and insulin-naïve adult T2DM subjects.

A theoretical model for the Gla-TSR-EGF-1 region of the anticoagulant cofactor protein S: From biostructural pathology to specie

NASA Astrophysics Data System (ADS)

Villoutreix, Bruno O.; Teleman, Olle; Dahlbäck, Björn

1997-05-01

Protein S (PS), which functions as a species-specific anticoagulant cofactor to activated protein C (APC), is a mosaic protein that interacts with the phospholipid membrane via its γ-carboxyglutamate-rich (Gla) module. This module is followed by the thrombin-sensitive region (TSR), sensitive to thrombin cleavage, four epidermal growth factor (EGF)-like modules and a last region referred to as the sex hormone binding globulin (SHBG) domain. Of these, the TSR and the first EGF-like regions have been shown to be important for the species-specific interaction with APC. Difficulties in crystallising PS have so far hindered its study at the atomic level. Here, we report theoretical models for the Gla and EGF-1 modules of human PS constructed using prothrombin and factor X experimental structures. The TSR was built interactively. Analysis of the model linked with the large body of biochemical literature on PS and related proteins leads to suggestions that (i) the TSR stabilises the calcium-loaded Gla module through hydrophobic and ionic interactions and its conformation depends on the presence of the Gla module; (ii) the TSR does not form a calcium binding site but is protected from thrombin cleavage in the calcium-loaded form owing to short secondary structure elements and close contact with the Gla module; (iii) the PS missense mutations in this region are consistent with the structural data, except in one case which needs further investigation; and (iv) the two PS `faces' involving regions of residues Arg49-Gln52-Lys97 (TSR-EGF-1) and Thr103-Pro106 (EGF-1) may be involved in species-specific interactions with APC as they are richer in nonconservative substitution when comparing human and bovine protein S. This preliminary model helps to plan future experiments and the resulting data will be used to further validate and optimise the present structure.

Efficacy of a 2-month dietary supplementation with polyunsaturated fatty acids in dry eye induced by scopolamine in a rat model.

PubMed

Viau, Sabrina; Maire, Marie-Annick; Pasquis, Bruno; Grégoire, Stéphane; Acar, Niyazi; Bron, Alain M; Bretillon, Lionel; Creuzot-Garcher, Catherine P; Joffre, Corinne

2009-08-01

This study was conducted to evaluate the efficacy of dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) in dry eye in a rat model. Female Lewis rats were fed with diets containing (1) gamma-linolenic acid (GLA), (2) eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), or (3) GLA + EPA + DHA, for 2 months before the induction of dry eye using a continuous delivery of scopolamine and during scopolamine treatment. Two, 10 and 28 days after dry-eye induction, clinical signs of corneal dryness were evaluated in vivo using fluorescein staining. MHC II expression and mucin rMuc5AC production in the conjunctival epithelium were evaluated by immunostaining. Lipids and prostaglandins (PGs) E(1) and E(2) were analysed from the exorbital lacrimal gland (LG). Dietary PUFAs minimised the occurrence of corneal keratitis 28 days after induction of dry eye. The decrease in mucin production observed on the conjunctival epithelium was partially prevented by EPA + DHA supplementation after 2 days of scopolamine treatment, as well as by GLA and GLA + EPA + DHA diets after 10 days of treatment. The overexpression of MHC II in the conjunctival epithelium caused by dry eye induction was significantly reduced only with the GLA + EPA + DHA diet after 28 days of treatment. Dietary PUFAs were incorporated into phospholipids of the exorbital LG. Induction of dry eye was associated with a significant increase in PGE(1) and PGE(2) levels in the exorbital LG, which was inhibited by dietary EPA + DHA at 10 days (for PGE(2)) and 28 days (for PGE(1)). Dietary GLA, EPA and DHA significantly interfered with lipid homeostasis in the exorbital LG and partially prevented the course of dry eye. In particular, our results demonstrate the efficacy of the combination of n-6 and n-3 PUFAs.

CBD binding domain fused γ-lactamase from Sulfolobus solfataricus is an efficient catalyst for (-) γ-lactam production.

PubMed

Wang, Jianjun; Zhu, Junge; Min, Cong; Wu, Sheng

2014-05-13

γ-lactamase is used for the resolution of γ-lactam which is utilized in the synthesizing of abacavir and peramivir. In some cases, enzymatic method is the most utilized method because of its high efficiency and productivity. The cellulose binding domain (CBD) of cellulose is often used as the bio-specific affinity matrix for enzyme immobilization. Cellulose is cheap and it has excellent chemical and physical properties. Meanwhile, binding between cellulose and CBD is tight and the desorption rarely happened. We prepared two fusion constructs of the γ-lactamase gene gla, which was from Sulfolobus solfataricus P2. These two constructs had Cbd (cellulose binding domain from Clostridium thermocellum) fused at amino or carboxyl terminus of the γ-lactamase. These two constructs were heterogeneously expressed in E. coli rosetta (DE3) as two fusion proteins. Both of them were immobilized well on Avicel (microcrystalline cellulose matrix). The apparent kinetic parameters revealed that carboxyl terminus fused protein (Gla-linker-Cbd) was a better catalyst. The V(max) and k(cat) value of Avicel immobilized Gla-linker-Cbd were 381 U mg⁻¹ and 4.7 × 10⁵ s⁻¹ respectively. And the values of the free Gla-linker-Cbd were 151 U mg⁻¹ and 1.8 × 10⁵ s⁻¹ respectively. These data indicated that the catalytic efficiency of the enzyme was upgraded after immobilization. The immobilized Gla-linker-Cbd had a 10-degree temperature optimum dropping from 80°C to 70°C but it was stable when incubated at 60°C for 48 h. It remained stable in catalyzing 20-batch reactions. After optimization, the immobilized enzyme concentration in transformation was set as 200 mg/mL. We found out that there was inhibition that occurred to the immobilized enzyme when substrate concentration exceeded 60 mM. Finally a 10 mL-volume transformation was conducted, in which 0.6 M substrate was hydrolyzed and the resolution was completed within 9 h with a 99.5% ee value. Cellulose is the most abundant and renewable material on the Earth. The absorption between Cbd domain and cellulose is a bio-green process. The cellulose immobilized fusion Gla exhibited good catalytic characters, therefore we think the cellulose immobilized Gla is a promising catalyst for the industrial preparation of (-) - γ-lactam.

Association between CYP4F2 genotype and circulating plasma vitamin K concentration in children on chronic warfarin therapy: Possible long-term implications for bone development and vascular health.

PubMed

Kampouraki, Emmanouela; Avery, Peter J; Biss, Tina; Kamali, Farhad

2017-12-01

Vitamin K is essential, for the activation of clotting proteins, as well as the biosynthesis of osteocalcin in bones and the activation of matrix-Gla protein needed in maintaining vasculature health. Cytochrome p450 4F2 (CYP4F2) enzyme is involved in vitamin K catabolism. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability. We show that children on chronic warfarin therapy have low levels of vitamin K and vitamin K levels are linked to CYP4F2 genotype. Long-term low levels of vitamin K, influenced by CYP4F2 genotype, might affect bone development and vascular health in children on chronic warfarin therapy. © 2017 Wiley Periodicals, Inc.

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms.

PubMed

Ponziani, Francesca Romana; Pompili, Maurizio; Di Stasio, Enrico; Zocco, Maria Assunta; Gasbarrini, Antonio; Flore, Roberto

2017-02-21

To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis. Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire. Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R 2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls. SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures.

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study

PubMed Central

2011-01-01

Introduction Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality. Methods Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period. Results A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patientsdeveloped cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79). Conclusions These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction. Trial Registration ClinicalTrials.gov: NCT00981877 PMID:21658240

Cloning of a novel thermostable glucoamylase from thermophilic fungus Rhizomucor pusillus and high-level co-expression with α-amylase in Pichia pastoris.

PubMed

He, Zhenggui; Zhang, Lujia; Mao, Youzhi; Gu, Jingchao; Pan, Qi; Zhou, Sixing; Gao, Bei; Wei, Dongzhi

2014-12-24

Fungal amylase, mainly constitute of fungal α-amylase and glucoamylase, are utilized in a broad range of industries, such as starch hydrolysis, food and brewing. Although various amylases have been found in fungi, the amylases from Aspergillus dominate the commercial application. One of main problems exist with regard to these commercial use of amylases is relatively low thermal and acid stability. In order to maximize the efficiency of starch process, developing fungal amylases with increased thermostability and acid stability has been attracting researchers' interest continually. Besides, synergetic action of glucoamylase and α-amylase could facilitate the degradation of starch. And co-expressing glucoamylase with α-amylase in one host could avoid the need to ferment repeatedly and improves cost-effectiveness of the process. A novel fungal glucoamylase (RpGla) gene encoding a putative protein of 512 amino acid residues was cloned from Rhizomucor pusillus. BLAST analysis revealed that RpGla shared highest identity of 51% with the Rhizopus oryzae glucoamylase (ABB77799.1). The fungal glucoamylase RpGla was expressed in Pichia pastoris (KM71/9KGla) with maximum activity of 1237 U ml(-1). The optimum pH and temperature of RpGla were pH 4.0 and 70 °C, respectively. Fungal α-amylase (RpAmy) gene was also cloned from R. pusillus and transformed into KM71/9KGla, resulted in recombinant yeast KM71/9KGla-ZαAmy harboring the RpGla and RpAmy genes simultaneously. The maximum saccharogenic activity of KM71/9KGla-ZαAmy was 2218 U ml(-1), which improved 79% compared to KM71/9KGla. Soluble starch hydrolyzed by purified RpGla achieved 43% glucose and 34% maltose. Higher productivity was achieved with a final yield of 48% glucose and 47% maltose catalyzed by purified enzyme preparation produced by KM71/9KGla-ZαAmy. A novel fungal glucoamylase and fungal α-amylase genes were cloned from Rhizomucor pusillus. The two enzymes showed good thermostability and acid stability, and similar biochemical properties facilitated synergetic action of the two enzymes. A dramatic improvement was seen in amylase activity through co-expressing RpGla with RpAmy in Pichia pastoris. This is the first report of improving activity through co-expression glucoamylase with α-amylase in P. pastoris. Besides, fungal glucoamylase and α-amylase from R. pusillus were shown as promising candidates for further application in starch hydrolysis.

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

PubMed

Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-Wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

2016-02-15

To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995-2017.

PubMed

Doheny, Dana; Srinivasan, Ram; Pagant, Silvere; Chen, Brenden; Yasuda, Makiko; Desnick, Robert J

2018-04-01

Fabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A ( GLA ) mutations, results in two major subtypes, the early-onset Type 1 'Classic' and the Type 2 'Later-Onset' phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised 'benign/likely-benign' variants, thereby inflating prevalence estimates. Online databases were searched for all FD screening studies in high-risk clinics (1995-2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined. Of 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9% of males and 74.1% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males and 0.14% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60%), except more male cardiac patients (75%) had type 2 Later-Onset phenotype. Compared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of stroke to ~0.9% of cardiac male or female screenees. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Raw starch conversion by Saccharomyces cerevisiae expressing Aspergillus tubingensis amylases

PubMed Central

2013-01-01

Background Starch is one of the most abundant organic polysaccharides available for the production of bio-ethanol as an alternative transport fuel. Cost-effective utilisation of starch requires consolidated bioprocessing (CBP) where a single microorganism can produce the enzymes required for hydrolysis of starch, and also convert the glucose monomers to ethanol. Results The Aspergillus tubingensis T8.4 α-amylase (amyA) and glucoamylase (glaA) genes were cloned and expressed in the laboratory strain Saccharomyces cerevisiae Y294 and the semi-industrial strain, S. cerevisiae Mnuα1. The recombinant AmyA and GlaA displayed protein sizes of 110–150 kDa and 90 kDa, respectively, suggesting significant glycosylation in S. cerevisiae. The Mnuα1[AmyA-GlaA] and Y294[AmyA-GlaA] strains were able to utilise 20 g l-1 raw corn starch as sole carbohydrate source, with ethanol titers of 9.03 and 6.67 g l-1 (0.038 and 0.028 g l-1 h-1), respectively, after 10 days. With a substrate load of 200 g l-1 raw corn starch, Mnuα1[AmyA-GlaA] yielded 70.07 g l-1 ethanol (0.58 g l-1 h-1) after 120 h of fermentation, whereas Y294[AmyA-GlaA] was less efficient at 43.33 g l-1 ethanol (0.36 g l-1 h-1). Conclusions In a semi-industrial amylolytic S. cerevisiae strain expressing the A. tubingensis α-amylase and glucoamylase genes, 200 g l-1 raw starch was completely hydrolysed (saccharified) in 120 hours with 74% converted to released sugars plus fermentation products and the remainder presumably to biomass. The single-step conversion of raw starch represents significant progress towards the realisation of CBP without the need for any heat pretreatment. Furthermore, the amylases were produced and secreted by the host strain, thus circumventing the need for exogenous amylases. PMID:24286270

Raw starch conversion by Saccharomyces cerevisiae expressing Aspergillus tubingensis amylases.

PubMed

Viktor, Marko J; Rose, Shaunita H; van Zyl, Willem H; Viljoen-Bloom, Marinda

2013-11-29

Starch is one of the most abundant organic polysaccharides available for the production of bio-ethanol as an alternative transport fuel. Cost-effective utilisation of starch requires consolidated bioprocessing (CBP) where a single microorganism can produce the enzymes required for hydrolysis of starch, and also convert the glucose monomers to ethanol. The Aspergillus tubingensis T8.4 α-amylase (amyA) and glucoamylase (glaA) genes were cloned and expressed in the laboratory strain Saccharomyces cerevisiae Y294 and the semi-industrial strain, S. cerevisiae Mnuα1. The recombinant AmyA and GlaA displayed protein sizes of 110-150 kDa and 90 kDa, respectively, suggesting significant glycosylation in S. cerevisiae. The Mnuα1[AmyA-GlaA] and Y294[AmyA-GlaA] strains were able to utilise 20 g l-1 raw corn starch as sole carbohydrate source, with ethanol titers of 9.03 and 6.67 g l-1 (0.038 and 0.028 g l-1 h-1), respectively, after 10 days. With a substrate load of 200 g l-1 raw corn starch, Mnuα1[AmyA-GlaA] yielded 70.07 g l-1 ethanol (0.58 g l-1 h-1) after 120 h of fermentation, whereas Y294[AmyA-GlaA] was less efficient at 43.33 g l-1 ethanol (0.36 g l-1 h-1). In a semi-industrial amylolytic S. cerevisiae strain expressing the A. tubingensis α-amylase and glucoamylase genes, 200 g l-1 raw starch was completely hydrolysed (saccharified) in 120 hours with 74% converted to released sugars plus fermentation products and the remainder presumably to biomass. The single-step conversion of raw starch represents significant progress towards the realisation of CBP without the need for any heat pretreatment. Furthermore, the amylases were produced and secreted by the host strain, thus circumventing the need for exogenous amylases.

Effect of two intermediate electron donors, NADPH and FADH(2), on Spirulina Delta (6)-desaturase co-expressed with two different immediate electron donors, cytochrome b (5) and ferredoxin, in Escherichia coli.

PubMed

Kurdrid, Pavinee; Subudhi, Sanjukta; Cheevadhanarak, Supapon; Tanticharoen, Morakot; Hongsthong, Apiradee

2007-12-01

When the gene desD encoding Spirulina Delta(6)-desaturase was heterologously expressed in E. coli, the enzyme was expressed without the ability to function. However, when this enzyme was co-expressed with an immediate electron donor, i.e. the cytochrome b (5) domain from Mucor rouxii, the results showed the production of GLA (gamma-linolenic acid), the product of the reaction catalyzed by Delta(6)-desaturase. The results revealed that in E. coli cells, where cytochrome b (5) is absent and ferredoxin, a natural electron donor of Delta(6)-desaturase, is present at a very low level, the cytochrome b (5) domain can complement for the function of ferredoxin in the host cells. In the present study, the Spirulina-ferredoxin gene was cloned and co-expressed with the Delta(6)-desaturase in E. coli. In comparison to the co-expression of cytochrome b ( 5 ) with the Delta(6)-desaturase, the co-expression with ferredoxin did not cause any differences in the GLA level. Moreover, the cultures containing the Delta(6)-desaturase co-expressed with cytochrome b (5) and ferredoxin were exogenously supplied with the intermediate electron donors, NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and FADH(2) (flavin adenine dinucleotide, reduced form), respectively. The GLA level in these host cells increased drastically, by approximately 50%, compared to the cells without the intermediate electron donors. The data indicated that besides the level of immediate electron donors, the level of intermediate electron donors is also critical for GLA production. Therefore, if the pools of the immediate and intermediate electron donors in the cells are manipulated, the GLA production in the heterologous host will be affected.

Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

PubMed

Becker, R H A; Nowotny, I; Teichert, L; Bergmann, K; Kapitza, C

2015-03-01

To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM). A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability. The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15-21] and 33.4% (95% CI 28-41), respectively. Reproducibility of the metabolic effect was lower than that of exposure. Gla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms

PubMed Central

Ponziani, Francesca Romana; Pompili, Maurizio; Di Stasio, Enrico; Zocco, Maria Assunta; Gasbarrini, Antonio; Flore, Roberto

2017-01-01

AIM To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis. METHODS Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylated-uncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire. RESULTS Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein (β = 0.220, R2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls. CONCLUSION SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures. PMID:28275304

The g.1170C>T polymorphism of the 5' untranslated region of the human alpha-galactosidase gene is associated with decreased enzyme expression--evidence from a family study.

PubMed

Oliveira, J P; Ferreira, S; Reguenga, C; Carvalho, F; Månsson, J-E

2008-12-01

Subnormal leukocyte α-galactosidase (α-Gal) activity was found during evaluation of an adolescent male with cryptogenic cerebrovascular small-vessel disease. The only molecular abnormality found was the g.1170C>T single-nucleotide polymorphism (SNP) in the 5' untranslated region of exon 1 in the α-Gal gene (GLA). Historically, this polymorphism has been considered to be biologically neutral. To test the hypothesis that the g.1170T allele might be associated with lower α-Gal expression, we genotyped GLA exon 1 and measured leukocyte and plasma α-Gal in the parents, brother and sister of the index case. The g.1170T allele co-segregated with a subnormal leukocyte α-Gal activity in the three siblings. Although plasma enzyme activities were within the normal range in all five relatives, the ranking of their values suggested a dosage effect of the g.1170T allele. Western blotting assays of leukocyte protein extracts showed that the relative expression of α-Gal in both the patient and his sister was significantly lower than in sex-matched hemizygous or homozygous controls for the g.1170C allele, either normalized to the β-actin immunoblot expression or standardized to a known amount of recombinant human α-Gal. These family data, in combination with results from a recent GLA SNP screening study among healthy Portuguese individuals, suggest that the g.1170C>T SNP may be co-dominantly associated with a relatively decreased GLA expression at the transcription and/or translation level. Larger population studies are needed to confirm these findings and to test the hypothesis that the GLA g.1170C>T may contribute to the multifactorial risk of ischaemic small-vessel cerebrovascular disease.

Impact of lysosomal storage disorders on biology of mesenchymal stem cells: Evidences from in vitro silencing of glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes.

PubMed

Squillaro, Tiziana; Antonucci, Ivana; Alessio, Nicola; Esposito, Anna; Cipollaro, Marilena; Melone, Mariarosa Anna Beatrice; Peluso, Gianfranco; Stuppia, Liborio; Galderisi, Umberto

2017-12-01

Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD), and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues. Since the impairment of MSC functions could pose profound consequences on body physiology, we evaluated whether GBA and GLA silencing could affect the biology of MSCs isolated from bone marrow and amniotic fluid. Those cell populations were chosen given the former's key role in organ physiology and the latter's intriguing potential as an alternative stem cell model for human genetic disease. Our results revealed that GBA and GLA deficiencies prompted cell cycle arrest along with the impairment of autophagic flux and an increase of apoptotic and senescent cell percentages. Moreover, an increase in ataxia-telangiectasia-mutated staining 1 hr after oxidative stress induction and a return to basal level at 48 hr, along with persistent gamma-H2AX staining, indicated that MSCs properly activated DNA repair signaling, though some damages remained unrepaired. Our data therefore suggest that MSCs with reduced GBA or GLA activity are prone to apoptosis and senescence due to impaired autophagy and DNA repair capacity. © 2017 Wiley Periodicals, Inc.

Optimization of medium components using orthogonal arrays for Linolenic acid production by Spirulina platensis

USDA-ARS?s Scientific Manuscript database

This work describes the medium optimization of '-Linolenic acid (GLA) production by Spirulina platensis using one-factor and orthogonal array design methods. In the one-factor experiments, NaHCO3 (9 mg L-1), NaNO3 (13.5 mg L-1) and MgSO4•7H2O (11.85 mg L-1) proved to be the best components for GLA p...

Combining global and local approximations

NASA Technical Reports Server (NTRS)

Haftka, Raphael T.

1991-01-01

A method based on a linear approximation to a scaling factor, designated the 'global-local approximation' (GLA) method, is presented and shown capable of extending the range of usefulness of derivative-based approximations to a more refined model. The GLA approach refines the conventional scaling factor by means of a linearly varying, rather than constant, scaling factor. The capabilities of the method are demonstrated for a simple beam example with a crude and more refined FEM model.

Hemizygous Fabry disease associated with membranous nephropathy: A rare case report
.

PubMed

Zhou, Wenyan; Ni, Zhaohui; Zhang, Minfang

2018-05-24

Fabry disease may coexist with various glomerular diseases, including IgA nephropathy, focal segmental glomerulosclerosis, etc. In this study, we report a rare case of Fabry disease associated with membranous nephropathy (MN). A 30-year-old man with nephrotic proteinuria, normal renal function, and no other extrarenal manifestations underwent a renal biopsy in February 2017. Light microscopy and immunofluorescence indicated MN (stage 1). Under an electron microscope, there were subepithelial electron-dense deposits and abundant zebra bodies in podocytes. Both the findings of low-activity α-galactosidase A (α-Gal A, GLA) and base deletion in exon 7 of the GLA gene (GLA-E07.1286_*7 del, a newly reported mutation) confirmed that this patient was simultaneously afflicted with Fabry disease. This case report is an important reminder of the role of kidney biopsy, especially electron microscopy, as an indicator of Fabry disease and its rare coexistence with MN.
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Effects of dietary supplementation with eicosapentaenoic acid or gamma-linolenic acid on neutrophil phospholipid fatty acid composition and activation responses.

PubMed

Fletcher, M P; Ziboh, V A

1990-10-01

Previous data that alimentation with fish oil rich in eicosapentaenoic acid (EPA; 20:n-3) or vegetable oil rich in gamma-linolenic acid (GLA; 18:3n-6) can reduce symptoms of inflammatory skin disorders lead us to determine the effects of dietary supplements of oils rich in EPA or GLA on guinea pig (GP) neutrophil (PMN) membrane potential (delta gamma), secretion, and superoxide (O2-) responses. Weanling GPs were initially fed diets supplemented with olive oil (less than 0.1% EPA; less than 0.1% GLA) for 2 weeks, followed by a crossover by two sets of animals to diets supplemented with fish oil (19% EPA) or borage oil (25% GLA). At 4-week intervals, 12% sterile casein-elicited peritoneal neutrophils (PMN) were assessed for membrane polyunsaturated fatty acid (PUFA) profiles and FMLP-, LTB4-, and PMA-stimulated delta gamma changes, changes in flow cytometrically measured forward scatter (FWD-SC) (shape change), 90 degrees scatter (90 degrees -SC) in cytochalasin B-pretreated-PMN (secretion response), and superoxide responses, GP incorporated EPA and GLA (as the elongation product, dihomo-GLA or DGLA) into their PMN phospholipids by 4 weeks. The peritoneal PMN of all groups demonstrated broad resting FWD-SC and poor activation-related FWD-SC increases, suggesting in vivo activation. While secretion was comparable in the three groups in response to FMLP, there was a trend toward inhibition of LTB4-stimulated 90 degrees -SC loss in both fish and borage oil groups. This was significant only with borage oil (21.7 +/- 2.1 vs 15.3 +/- 1.2% loss of baseline 90 degrees -SC, olive vs borage: P = 0.03). PMN from borage- and fish oil-fed GPs showed a progressively lower O2- response to FMLP than the olive oil group (73.9 +/- 3.9 and 42.9 +/- 6.8% of olive oil response for borage and fish oils, respectively; P less than 0.005 and P less than 0.01, respectively, at 12 weeks), while PMA-stimulated O2- was inhibited only in the fish oil-fed group and only at 12 weeks (62.0 +/- 2.7% of control; P less than 0.025). We conclude that dietary supplementation with oils rich in PUFAs can modify PMN activation responses.

Analysis of Suitability for Development of New Mining Field in Northern Part of Kosovo Lignite Basin - Sibovc / Analiza Możliwości Udostępnienia Nowego Obszaru Wybierania W Północnej Części Zagłębia Węgla Brunatnego Sibovc W Kosowie

NASA Astrophysics Data System (ADS)

Cehlár, Michal; Rybár, Radim; Pinka, Ján; Haxhiu, Lorik; Beer, Martin

2013-06-01

This review describes the possibility of development a new lignite deposit in northern Kosovo lignite basin - Sibovc. Analysis of the initial state briefly evaluates Kosovo energy sector, geomorphological conditions and quality of lignite from Sibovc deposit. With using Dataminesoft it was created geological model and approximate calculation of lignite reserves in the deposit. The data obtained from Dataminesoft were used as starting points of the financial analysis of project. The result of the analysis is exactly describe the qualitative and quantitative characteristics of deposit Sibovc compared to other deposits in the area and creating of geological model with productive horizons deposit of lignite. Based on these data lignite deposit Sibovc was classified, according to the classification of deposits the UN, as economical. W pracy tej omówiono możliwości udostępnienia nowego obszaru wybierania złoża węgla brunatnego (lignitu) w północnej części zagłębia węgla brunatnego Sibovc w Kosowie. W analizie stanu początkowego krótko scharakteryzowano sektor energetyczny Kosowa, warunki geo-morfologiczne oraz parametry jakościowe węgla brunatnego z zagłębia Sibovc. Przy pomocy pakietu Dataminesoft stworzono model geologiczny i przeprowadzono przybliżone obliczenia zasobów węgla brunatnego w złożu. Dane uzyskane przy zastosowaniu pakietu Dataminesoft zostały następnie wykorzystane jako dane wejściowe do analizy finansowej przedsięwzięcia. Na podstawie wyników analizy uzyskuje się jakościową i ilościową charakterystykę złoża w odniesieniu do pozostałych złóż w regionie. Opracowano model geologiczny ze szczegółowym wskazaniem poziomów wybierania lignitu. W oparciu o te dane dokonano klasyfikacji złoża węgla brunatnego (lignitu) w Sibovc zgodnie z międzynarodowymi zasadami klasyfikacji wykazując, że złoże będzie ekonomiczne.

Gla-Rich Protein Is a Potential New Vitamin K Target in Cancer: Evidences for a Direct GRP-Mineral Interaction

PubMed Central

Viegas, Carla S. B.; Herfs, Marjolein; Rafael, Marta S.; Enriquez, José L.; Teixeira, Alexandra; Luís, Inês M.; van ‘t Hoofd, Cynthia M. R.; João, Alexandre; Maria, Vera L.; Cavaco, Sofia; Ferreira, Ana; Serra, Manuel; Theuwissen, Elke; Vermeer, Cees; Simes, Dina C.

2014-01-01

Gla-rich protein (GRP) was described in sturgeon as a new vitamin-K-dependent protein (VKDP) with a high density of Gla residues and associated with ectopic calcifications in humans. Although VKDPs function has been related with γ-carboxylation, the Gla status of GRP in humans is still unknown. Here, we investigated the expression of recently identified GRP spliced transcripts, the γ-carboxylation status, and its association with ectopic calcifications, in skin basal cell and breast carcinomas. GRP-F1 was identified as the predominant splice variant expressed in healthy and cancer tissues. Patterns of γ-carboxylated GRP (cGRP)/undercarboxylated GRP (ucGRP) accumulation in healthy and cancer tissues were determined by immunohistochemistry, using newly developed conformation-specific antibodies. Both GRP protein forms were found colocalized in healthy tissues, while ucGRP was the predominant form associated with tumor cells. Both cGRP and ucGRP found at sites of microcalcifications were shown to have in vitro calcium mineral-binding capacity. The decreased levels of cGRP and predominance of ucGRP in tumor cells suggest that GRP may represent a new target for the anticancer potential of vitamin K. Also, the direct interaction of cGRP and ucGRP with BCP crystals provides a possible mechanism explaining GRP association with pathological mineralization. PMID:24949434

A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation.

PubMed

Voziyan, Paul A; Metz, Thomas O; Baynes, John W; Hudson, Billy G

2002-02-01

Reactive carbonyl compounds are formed during autoxidation of carbohydrates and peroxidation of lipids. These compounds are intermediates in the formation of advanced glycation end products (AGE) and advanced lipoxidation end products (ALE) in tissue proteins during aging and in chronic disease. We studied the reaction of carbonyl compounds glyoxal (GO) and glycolaldehyde (GLA) with pyridoxamine (PM), a potent post-Amadori inhibitor of AGE formation in vitro and of development of renal and retinal pathology in diabetic animals. PM reacted rapidly with GO and GLA in neutral, aqueous buffer, forming a Schiff base intermediate that cyclized to a hemiaminal adduct by intramolecular reaction with the phenolic hydroxyl group of PM. This bicyclic intermediate dimerized to form a five-ring compound with a central piperazine ring, which was characterized by electrospray ionization-liquid chromatography/mass spectrometry, NMR, and x-ray crystallography. PM also inhibited the modification of lysine residues and loss of enzymatic activity of RNase in the presence of GO and GLA and inhibited formation of the AGE/ALE N(epsilon)-(carboxymethyl)lysine during reaction of GO and GLA with bovine serum albumin. Our data suggest that the AGE/ALE inhibitory activity and the therapeutic effects of PM observed in diabetic animal models depend, at least in part, on its ability to trap reactive carbonyl intermediates in AGE/ALE formation, thereby inhibiting the chemical modification of tissue proteins.

Development of Aeroservoelastic Analytical Models and Gust Load Alleviation Control Laws of a SensorCraft Wind-Tunnel Model Using Measured Data

NASA Technical Reports Server (NTRS)

Silva, Walter A.; Vartio, Eric; Shimko, Anthony; Kvaternik, Raymond G.; Eure, Kenneth W.; Scott,Robert C.

2007-01-01

Aeroservoelastic (ASE) analytical models of a SensorCraft wind-tunnel model are generated using measured data. The data was acquired during the ASE wind-tunnel test of the HiLDA (High Lift-to-Drag Active) Wing model, tested in the NASA Langley Transonic Dynamics Tunnel (TDT) in late 2004. Two time-domain system identification techniques are applied to the development of the ASE analytical models: impulse response (IR) method and the Generalized Predictive Control (GPC) method. Using measured control surface inputs (frequency sweeps) and associated sensor responses, the IR method is used to extract corresponding input/output impulse response pairs. These impulse responses are then transformed into state-space models for use in ASE analyses. Similarly, the GPC method transforms measured random control surface inputs and associated sensor responses into an AutoRegressive with eXogenous input (ARX) model. The ARX model is then used to develop the gust load alleviation (GLA) control law. For the IR method, comparison of measured with simulated responses are presented to investigate the accuracy of the ASE analytical models developed. For the GPC method, comparison of simulated open-loop and closed-loop (GLA) time histories are presented.

Development of Aeroservoelastic Analytical Models and Gust Load Alleviation Control Laws of a SensorCraft Wind-Tunnel Model Using Measured Data

NASA Technical Reports Server (NTRS)

Silva, Walter A.; Shimko, Anthony; Kvaternik, Raymond G.; Eure, Kenneth W.; Scott, Robert C.

2006-01-01

Aeroservoelastic (ASE) analytical models of a SensorCraft wind-tunnel model are generated using measured data. The data was acquired during the ASE wind-tunnel test of the HiLDA (High Lift-to-Drag Active) Wing model, tested in the NASA Langley Transonic Dynamics Tunnel (TDT) in late 2004. Two time-domain system identification techniques are applied to the development of the ASE analytical models: impulse response (IR) method and the Generalized Predictive Control (GPC) method. Using measured control surface inputs (frequency sweeps) and associated sensor responses, the IR method is used to extract corresponding input/output impulse response pairs. These impulse responses are then transformed into state-space models for use in ASE analyses. Similarly, the GPC method transforms measured random control surface inputs and associated sensor responses into an AutoRegressive with eXogenous input (ARX) model. The ARX model is then used to develop the gust load alleviation (GLA) control law. For the IR method, comparison of measured with simulated responses are presented to investigate the accuracy of the ASE analytical models developed. For the GPC method, comparison of simulated open-loop and closed-loop (GLA) time histories are presented.

Identification of novel mutations in the α-galactosidase A gene in patients with Fabry disease: pitfalls of mutation analyses in patients with low α-galactosidase A activity.

PubMed

Yoshimitsu, Makoto; Higuchi, Koji; Miyata, Masaaki; Devine, Sean; Mattman, Andre; Sirrs, Sandra; Medin, Jeffrey A; Tei, Chuwa; Takenaka, Toshihiro

2011-05-01

Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A (GLA) gene, and the disease is a relatively prevalent cause of left ventricular hypertrophy followed by conduction abnormalities and arrhythmias. Mutation analysis of the GLA gene is a valuable tool for accurate diagnosis of affected families. In this study, we carried out molecular studies of 10 unrelated families diagnosed with Fabry disease. Genetic analysis of the GLA gene using conventional genomic sequencing was performed in 9 hemizygous males and 6 heterozygous females. In patients with no mutations in coding DNA sequence, multiplex ligation-dependent probe amplification (MLPA) and/or cDNA sequencing were performed. We identified a novel exon 2 deletion (IVS1_IVS2) in a heterozygous female by MLPA, which was undetectable by conventional sequencing methods. In addition, the g.9331G>A mutation that has previously been found only in patients with cardiac Fabry disease was found in 3 unrelated, newly-diagnosed, cardiac Fabry patients by sequencing GLA genomic DNA and cDNA. Two other novel mutations, g.8319A>G and 832delA were also found in addition to 4 previously reported mutations (R112C, C142Y, M296I, and G373D) in 6 other families. We could identify GLA gene mutations in all hemizygotes and heterozygotes from 10 families with Fabry disease. Mutations in 4 out of 10 families could not be identified by classical genomic analysis, which focuses on exons and the flanking region. Instead, these data suggest that MLPA analysis and cDNA sequence should be considered in genetic testing surveys of patients with Fabry disease. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Serum concentrations of carboxylated osteocalcin are increased and associated with several components of the polycystic ovarian syndrome.

PubMed

Diamanti-Kandarakis, Evanthia; Livadas, Sarantis; Katsikis, Ilias; Piperi, Christine; Mantziou, Aimilia; Aimilia, Mantziou; Papavassiliou, Athanasios G; Panidis, Dimitrios

2011-03-01

Intriguing studies suggest that osteocalcin (OC) and its carboxylated (Gla)/uncarboxylated form are involved in the regulation of insulin secretion and action. Additionally, advanced glycated end products (AGEs) directly regulate the secretion of these osteoblast-derived molecules. In polycystic ovarian syndrome (PCOS), among the pathophysiological aberrations, deregulation of insulin secretion and action as well as elevated AGEs levels have been demonstrated. In this study, we evaluated the serum levels of osteocalcin and Gla osteocalcin and their possible associations with metabolic, hormonal, and ultrasonographic components of PSOS: 97 women were studied, 50 PCOS patients and 47 controls, matched for age and body mass index (BMI). In each subject, the levels of bone metabolism markers have been evaluated, and metabolic and hormonal profiles as well as ovarian ultrasound were carried out. Osteocalcin (4.30 ± 1.74 vs. 6.20 ± 1.78 ng/ml, P < 0.0005) values were significantly lower, whereas Gla osteocalcin (37.93 ± 6.87 vs. 9.64 ± 8.21 ng/ml, P < 0.0005) and receptor activator for nuclear factor-κB ligand (0.54 ± 0.26 vs. 0.16 ± 0.15 pmol/l, P < 0.0005) values were significantly higher in PCOS subjects compared to the control group, independently of obesity. A significant association was disclosed between osteocalcin and Gla osteocalcin with androgens, insulin resistance, AGEs, and ovarian morphology. Receiver operating curve analysis revealed that Gla osteocalcin [AUC, 0.975 (95% CI, 0.93-1.00)] as well as AGEs are significant prognostic factors of PCOS [AUC, 0.986 (95% CI, 0.97-1.00)]. Lower osteocalcin and elevated serum levels of its carboxylated form are displayed in PCOS subjects and are associated with several PCOS components. These findings suggest a potential interaction between bone-derived markers and the metabolic/hormonal abnormalities observed in PCOS. However, the pathophysiological mechanisms and moreover the possible clinical implications require further investigation.

Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

PubMed Central

Sohn, Youngsoo; Lee, Jung Mi; Park, Heung-Rok; Jung, Sung-Chul; Park, Tai Hyun; Oh, Doo-Byoung

2013-01-01

Human α-galactosidase A (GLA) has been used in enzyme replacement therapy for patients with Fabry disease. We expressed recombinant GLA from Chinese hamster ovary cells with very high productivity. When compared to an approved GLA (agalsidase beta), its size and charge were found to be smaller and more neutral. These differences resulted from the lack of terminal sialic acids playing essential roles in the serum half-life and proper tissue targeting. Because a simple sialylation reaction was not enough to increase the sialic acid content, a combined reaction using galactosyltransferase, sialyltransferase, and their sugar substrates at the same time was developed and optimized to reduce the incubation time. The product generated by this reaction had nearly the same size, isoelectric points, and sialic acid content as agalsidase beta. Furthermore, it had better in vivo efficacy to degrade the accumulated globotriaosylceramide in target organs of Fabry mice compared to an unmodified version. [BMB Reports 2013; 46(3): 157-162] PMID:23527859

High production of llama variable heavy-chain antibody fragment (VHH) fused to various reader proteins by Aspergillus oryzae.

PubMed

Hisada, Hiromoto; Tsutsumi, Hiroko; Ishida, Hiroki; Hata, Yoji

2013-01-01

Llama variable heavy-chain antibody fragment (VHH) fused to four different reader proteins was produced and secreted in culture medium by Aspergillus oryzae. These fusion proteins consisted of N-terminal reader proteins, VHH, and a C-terminal his-tag sequence which facilitated purification using one-step his-tag affinity chromatography. SDS-PAGE analysis of the deglycosylated purified fusion proteins confirmed that the molecular weight of each corresponded to the expected sum of VHH and the respective reader proteins. The apparent high molecular weight reader protein glucoamylase (GlaB) was found to be suitable for efficient VHH production. The GlaB-VHH-His protein bound its antigen, human chorionic gonadotropin, and was detectable by a new ELISA-based method using a coupled assay with glucoamylase, glucose oxidase, peroxidase, maltose, and 3,3',5,5'-tetramethylbenzidine as substrates. Addition of potassium phosphate to the culture medium induced secretion of 0.61 mg GlaB-VHH-His protein/ml culture medium in 5 days.

Enzymatic Synthesis of Refined Olive Oil-Based Structured Lipid Containing Omega -3 and -6 Fatty Acids for Potential Application in Infant Formula.

PubMed

Li, Ruoyu; Sabir, Jamal S M; Baeshen, Nabih A; Akoh, Casimir C

2015-11-01

Structured lipids (SLs) containing palmitic, docosahexaenoic (DHA), and gamma-linolenic (GLA) acids were produced using refined olive oil, tripalmitin, and ethyl esters of DHA single cell oil and GLA ethyl esters. Immobilized Lipozyme TL IM lipase was used as the biocatalyst. The SLs were characterized for fatty acid profile, triacylglycerol (TAG) molecular species, solid fat content, oxidative stability index, and melting and crystallization profiles and compared to physical blend of substrates, extracted fat from commercial infant formula (IFF), and milk fat. 49.28 mol% of palmitic acid was found at the sn-2 position of SL TAG and total DHA and GLA composition were 0.73 and 5.00 mol%, respectively. The total oleic acid content was 36.13 mol% which was very close to the 30.49% present in commercial IFF. Comparable solid fat content profiles were also found between SLs and IFF. The SLs produced have potential for use in infant formulas. © 2015 Institute of Food Technologists®

Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers.

PubMed

Ding, Zhen; Liu, Guo-Liang; Li, Xiang; Chen, Xue-Yan; Wu, Yi-Xia; Cui, Can-Can; Zhang, Xi; Yang, Guang; Xie, Lin

2016-06-01

The fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. Evaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. A SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535-rs174575) in the FADS2 gene were associated with concentrations of γ-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3-locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. Polymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhancement of nutritionally significant constituents of black currant seeds by chemical elicitor application.

PubMed

Flores, Gema; Ruiz del Castillo, María Luisa

2016-03-01

Black currant seeds are obtained as a residue during juice production. Black currant seed oil contains high amounts of nutritionally desirable constituents such as γ-linolenic acid (GLA), α-linolenic acid (ALA) and stearidonic acid (SA), as well as certain phenolic acids, which act as natural antioxidants. Fatty acids and phenolic acids of seeds from black currant cultivars after elicitation with methyl jasmonate (MJ) were examined. GLA contents around 25% with respect to total fatty acid content were measured in seeds after pre-harvest treatment of black currants with 0.02mM MJ in 0.05% Tween-20. High GLA samples also exhibited high SA content (higher than 10% with respect to total fatty acid content); however, ALA dropped (from 16% to 10%). High GLA content seeds also showed increased contents of gallic, caffeic, p-coumaric and ferulic acids. In particular, seeds from 0.02mM MJ treated Ben Hope black currants exerted contents of gallic, caffeic, p-coumaric and ferulic acids of 201.4, 125.9, 201.3 and 112.5μgg(-1)vs 124.3, 58.6, 165.4 and 95.8μgg(-1) measured in seeds from untreated Ben Hope black currants. Comparable results were obtained for Ben Alder and Ben Gairn berries. Chemical elicitation with 0.02 MJ is proposed as an industrial practice in such a way that, after consideration of quality issues, it would be obtained high added value black currant seeds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PubMed

Maruyama, Hiroki; Miyata, Kaori; Mikame, Mariko; Taguchi, Atsumi; Guili, Chu; Shimura, Masaru; Murayama, Kei; Inoue, Takeshi; Yamamoto, Saori; Sugimura, Koichiro; Tamita, Koichi; Kawasaki, Toshihiro; Kajihara, Jun; Onishi, Akifumi; Sugiyama, Hitoshi; Sakai, Teiko; Murata, Ichijiro; Oda, Takamasa; Toyoda, Shigeru; Hanawa, Kenichiro; Fujimura, Takeo; Ura, Shigehisa; Matsumura, Mimiko; Takano, Hideki; Yamashita, Satoshi; Matsukura, Gaku; Tazawa, Ryushi; Shiga, Tsuyoshi; Ebato, Mio; Satoh, Hiroshi; Ishii, Satoshi

2018-03-15

PurposePlasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.MethodsBetween 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.ResultsOf 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml -1 ) and low α-Gal A activity (≤4.0 nmol h -1  ml -1 ), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).ConclusionPlasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.Genet Med advance online publication, 15 March 2018; doi:10.1038/gim.2018.31.

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

PubMed Central

Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

2015-01-01

Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

Vitamin K: from coagulation to calcification.

PubMed

Paakkari, Ilari

Vitamin K is not only essential for the synthesis of coagulation factors in the liver, but it also strengthens the bones and prevents calcification of the arteries. These effects are mediated through the same mechanism, i.e. carboxylation of Gla target proteins. The discovery of novel Gla proteins that are not associated with blood coagulation or calcium metabolism indicates that vitamin K has additional effects in the pancreas and the central nervous system, for example. As dietary supplements, vitamin K1 of plant origin and vitamins K2 of bacterial origin may exert different effects.

The roles of dry convection, cloud-radiation feedback processes and the influence of recent improvements in the parameterization of convection in the GLA GCM

NASA Technical Reports Server (NTRS)

Sud, Y.; Molod, A.

1988-01-01

The Goddard Laboratory for Atmospheres GCM is used to study the sensitivity of the simulated July circulation to modifications in the parameterization of dry and moist convection, evaporation from falling raindrops, and cloud-radiation interaction. It is shown that the Arakawa-Schubert (1974) cumulus parameterization and a more realistic dry convective mixing calculation yielded a better intertropical convergence zone over North Africa than the previous convection scheme. It is found that the physical mechanism for the improvement was the upward mixing of PBL moisture by vigorous dry convective mixing. A modified rain-evaporation parameterization which accounts for raindrop size distribution, the atmospheric relative humidity, and a typical spatial rainfall intensity distribution for convective rain was developed and implemented. This scheme led to major improvements in the monthly mean vertical profiles of relative humidity and temperature, convective and large-scale cloudiness, rainfall distributions, and mean relative humidity in the PBL.

[Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function].

PubMed

Komai, Michio; Shirakawa, Hitoshi

2007-11-01

Phylloquinone (vitamin K(1) = VK(1)) and the menaquinones (MK-n, or vitamin K(2) = VK(2)) are naturally occurring forms of VK. Most of the menaquinone series are synthesized by microorganisms, but we have reported that MK-4 is usual in being synthesized by the conversion of orally ingested VK(1) or MK-n in the major tissues of germfree rats and mice which lack their intestinal microflora. This result led us to deny 1960's Martius' hypothesis that described the participation of bacterial enzyme of the intestinal flora to this conversion. VK acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic acid (Gla) from glutamic acid (Glu) residues in the nascent Gla-protein molecule. Therefore, VK is essential for blood coagulation (various clotting factors) and bone structure (as osteocalcin [OC = BGP] and matrix Gla-protein [MGP] in mammals. In addition to the liver, VK is found in the bone, brain, heart, testis, kidney, pancreas and salivary glands mainly as MK-4, and it has been reported that MK-4 itself has specific biological activities in these tissues beside Gla-protein formation. However, the physiological role of MK-4 in these organs has not been fully understood yet. Recently MK-4 has been attracted the attention of researchers due to its activities such as apoptotic activity on the osteoclast cells and leukemia cells, SXR/PXR ligand, and so on. We further review the potent important physiological role of MK-4 in the bone as well as other major tissues.

A stimuli-responsive fluorescence platform for simultaneous determination of D-isoascorbic acid and Tartaric acid based on Maillard reaction product

NASA Astrophysics Data System (ADS)

Zhao, Yanmei; Yuan, Haiyan; Zhang, Xinling; Yang, Jidong

2018-05-01

An activatable fluorescence monitoring platform based on a novel Maillard reaction product from D-glucose and L-arginine was prepared through a facile one-pot approach and applied for simultaneous detection of D-isoascorbic acid and tartaric acid. In this work, the new Maillard reaction product GLA was first obtained, and its fluorescence intensity can be effectively quenched by KMnO4, resulting from a new complex (GLA-KMnO4) formation between GLA and KMnO4. Upon addition of D-isoascorbic acid or tartaric acid, an enhanced fluorescence was observed under the optimumed experimental conditions, indicating a stimuli-responsive fluorescence turn on platform for D-isoascorbic acid or tartaric acid can be developed. The corresponding experimental results showed that this turn on fluorescence sensing platform has a high sensitivity for D-isoascorbic acid or tartaric acid, because the detection limits were 5.9 μM and 21.5 μM, respectively. Additionally, this proposed sensing platform was applied to simultaneously detection of D-isoascorbic acid and tartaric acid in real tap water samples with satisfactory results.

Stabilized chitosan/Fe(0)-nanoparticle beads to remove heavy metals from polluted sediments.

PubMed

Liu, T; Sun, Y; Wang, Z L

2016-01-01

Sediment contamination by heavy metals has become a widespread problem that can affect the normal behaviors of rivers and lakes. After chitosan/Fe(0)-nanoparticles (CS-NZVI) beads were cross-linked with glutaraldehyde (GLA), their mechanical strength, stability and separation efficiency from the sediment were obviously improved. Moreover, the average aperture size of GLA-CS-NZVI beads was 20.6 μm and NZVI particles were nearly spherical in shape with a mean diameter of 40.2 nm. In addition, the pH showed an insignificant effect on the removal rates from the sediment. Due to the dissolution of metals species into aqueous solutions as an introduction of the salt, the removal rates of all heavy metals from the sediment were increased with an increase of the salinity. The competitive adsorption of heavy metals between the sediment particles and GLA-CS-NZVI beads became stronger as the sediment particles became smaller, leading to decreased removal rates. Therefore, the removal efficiency could be enhanced by optimizing experimental conditions and choosing appropriate materials for the target contaminants.

Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus.

PubMed

Sardana, Mayank; Vasim, Izzah; Varakantam, Swapna; Kewan, Uzma; Tariq, Ali; Koppula, Maheshwara R; Syed, Amer Ahmed; Beraun, Melissa; Drummen, Nadja E A; Vermeer, Cees; Akers, Scott R; Chirinos, Julio A

2017-02-01

Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes. We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands). The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use. In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Introduction to the Solid State Based Interior Lighting System for ISS

NASA Technical Reports Server (NTRS)

Maida, James C.

2014-01-01

Solid state lighting assembly (SSLA) were designed to replace general luminaire assembly (GLA) for both general interior illumination and improved circadian rhythm through melatonin control using multiple spectrums. To accomplish these goals, the light is design to operate in 3 modes with 3 distinct spectrum. The different spectrum provide control of the blue portion of the light which impacts melatonin production in humans which impacts sleep. General mode is a 4500K "neutral" light spectrum intended to the be the default mode of operation for day to day operations. Pre-sleep mode is a 2700K "warm" light spectrum intended to be used by the crew at the end of the work day. Phase-shift mode is a 6500K "cool" light spectrum intended to be used for altering the crew's sleep patterns.

Risk of death in heart disease is associated with elevated urinary globotriaosylceramide.

PubMed

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A; Taylor, Matthew R G; Lowes, Brian D; Fuller, Maria; Benjamin, Elfrida R; Sweetman, Lawrence

2014-02-04

Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X-linked lysosomal disorder that is a risk factor for most types of heart disease. We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α-galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow-up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near-term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. clinicaltrials.gov. Unique Identifier: NCT01019629.

Risk of Death in Heart Disease is Associated With Elevated Urinary Globotriaosylceramide

PubMed Central

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J.; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A.; Taylor, Matthew R. G.; Lowes, Brian D.; Fuller, Maria; Benjamin, Elfrida R.; Sweetman, Lawrence

2014-01-01

Background Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X‐linked lysosomal disorder that is a risk factor for most types of heart disease. Methods and Results We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α‐galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow‐up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). Conclusions In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near‐term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. Clinical Trial Registration URL: clinicaltrials.gov. Unique Identifier: NCT01019629. PMID:24496231

Gust prediction via artificial hair sensor array and neural network

NASA Astrophysics Data System (ADS)

Pankonien, Alexander M.; Thapa Magar, Kaman S.; Beblo, Richard V.; Reich, Gregory W.

2017-04-01

Gust Load Alleviation (GLA) is an important aspect of flight dynamics and control that reduces structural loadings and enhances ride quality. In conventional GLA systems, the structural response to aerodynamic excitation informs the control scheme. A phase lag, imposed by inertia, between the excitation and the measurement inherently limits the effectiveness of these systems. Hence, direct measurement of the aerodynamic loading can eliminate this lag, providing valuable information for effective GLA system design. Distributed arrays of Artificial Hair Sensors (AHS) are ideal for surface flow measurements that can be used to predict other necessary parameters such as aerodynamic forces, moments, and turbulence. In previous work, the spatially distributed surface flow velocities obtained from an array of artificial hair sensors using a Single-State (or feedforward) Neural Network were found to be effective in estimating the steady aerodynamic parameters such as air speed, angle of attack, lift and moment coefficient. This paper extends the investigation of the same configuration to unsteady force and moment estimation, which is important for active GLA control design. Implementing a Recurrent Neural Network that includes previous-timestep sensor information, the hair sensor array is shown to be capable of capturing gust disturbances with a wide range of periods, reducing predictive error in lift and moment by 68% and 52% respectively. The L2 norms of the first layer of the weight matrices were compared showing a 23% emphasis on prior versus current information. The Recurrent architecture also improves robustness, exhibiting only a 30% increase in predictive error when undertrained as compared to a 170% increase by the Single-State NN. This diverse, localized information can thus be directly implemented into a control scheme that alleviates the gusts without waiting for a structural response or requiring user-intensive sensor calibration.

Screening for Fabry disease in left ventricular hypertrophy: documentation of a novel mutation.

PubMed

Baptista, Ana; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio

2015-08-01

Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test - [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5).

Development and hydrology of biological soil crusts -- first results from a surface inoculation experiment

NASA Astrophysics Data System (ADS)

Mykhailova, Larysa; Raab, Thomas; Gypser, Stella; Fischer, Thomas

2016-04-01

Representing a set of various micro-biocoenoses, biocrusts often reside in adjacent patches, which not necessarily relate to structural elements of the habitat, like (micro-) topography or vegetational patterns. Such biocrust patches may become more stable through the formation of mutually dependent ecohydrological regimes. For example, algal patches inhibiting infiltration and generating runoff alternate with runoff-receiving moss patches possessing high water holding capacities. Here, we preliminarily report on a lysimeter field experiment where natural biocrust isolates were used for surface inoculation to (I) prove stochastic vs. deterministic biocrust development and (II) to quantitatively relate biocrust development to soil hydrology. Lysimeter sand was collected from 3-4 m below surface at natural dune outcrops in south-eastern Brandenburg, Germany (Glashütte (GLA) and Neuer Lugteich (LUG)), where biocrust samples were collected at the respective dune bases. The lysimeters were designed to prevent runoff. In a completely randomized full-factorial design, three factors were considered. (A) Inocolum in three treatments (bare control, mosses, algae), (B) mineral substrate texture in two treatments (GLA: 55% and LUG: 79% particles >630 μm), and (C) surface compaction in two treatments (control, 41.5 kN m-2 for 30 seconds). The samples were kept dry and re-moistened to -60 hPa two days before inoculation. After a species inventory, the inoculate was isolated by gently washing off sand particles from the biocrust samples. Algal/lichen crusts were dominated by Zygogonium ericetorum and Cladonia sp. at both sites. All moss crusts were dominated by Polytrichum piliferum and Ceratodon purpureus, whereas Brachythecium albicans was present at GLA only. 20 g of homogenized moist inoculate were spread over the surface of each lysimeter (Ø 19 cm, 22 cm depth). We performed autochthonous inoculation, i.e. biocrust isolates collected from GLA were used for inoculation of GLA substrate etc. The experiment started at 12.02.2015 and was located at an open area in the vicinity of a meteorological station, where all relevant for HYDRUS modeling data, as well as global radiation have been recorded every 10 min. Crust development was monitored by non-destructive NDVI imaging and a per lysimeter determination of the areal share of biocrust developmental stages: mineral surface (NDVI ≤ 0), BSC1 (0 < NDVI ≤ 0.15), BSC2 (0.15 < NDVI ≤ 0.40) and BSC3 (NDVI > 0.40). The general water balance equation and the amount of lysimeter leachate were used to determine evaporation and changes in water stocks by regular weighing. Biomass growth was inhibited in summer compared to autumn, where mosses developed faster than algae. Finer grained substrate promoted biocrust growth. Evapotranspiration increased with biomass development, presumably because the amount of water held close to the surface increased with biomass. It can be expected that this effect strengthens with increasing amounts of silt and clay. Biodiversity studies are pending, but incipient biocrust growth in the controls points to atmogenic superinfection. So far, it can be concluded that availability of water, depending on both precipitation and substrate texture, were the driving factors of biocrust development. Apart from runoff losses in hillslope conditions, biocrusts are hypothesized to take advantage over their vascular competitors by preventing water infiltration into deeper soil through increased evapotranspiration.

Fabry disease in children: correlation between ocular manifestations, genotype and systemic clinical severity.

PubMed

Allen, L E; Cosgrave, E M; Kersey, J P; Ramaswami, U

2010-12-01

Fabry disease is an X linked lysosomal disorder associated with severe multiorgan failure and premature death. This study aims to determine the prevalence of ophthalmic manifestations in children with the condition and investigate the correlation with genotype and systemic disease severity. The records of 26 children from 18 pedigrees with Fabry disease undergoing regular ophthalmic and systemic examination were reviewed. All pedigrees underwent GLA gene sequencing to determine genotype. Correlations between ocular and systemic phenotype and genotype were investigated. Corneal verticillata occurred in 50% of the children in this study (95% CI, 29% to 79%). Children with ophthalmic manifestations were more likely to have loss-of-function GLA mutations (p=0.003). Retinal vascular tortuosity was seen in seven children (27%), all of whom had systemic symptoms suggestive of autonomic neuropathy, such as diarrhoea and syncope. These symptoms seemed less prevalent in children without retinal vascular changes, although this did not reach statistical significance (p=0.134). Ophthalmic manifestations of Fabry disease are common even in young children with loss-of-function GLA gene mutations. Although the limited sample size possibly prevented statistical significance, systemic symptoms of autonomic neuropathy often coexist with retinal vascular changes and may share the same pathogenesis.

Production of γ-linolenic acid and stearidonic acid by Synechococcus sp. PCC7002 containing cyanobacterial fatty acid desaturase genes

NASA Astrophysics Data System (ADS)

Dong, Xuewei; He, Qingfang; Peng, Zhenying; Yu, Jinhui; Bian, Fei; Li, Youzhi; Bi, Yuping

2016-07-01

Genetic modification is useful for improving the nutritional qualities of cyanobacteria. To increase the total unsaturated fatty acid content, along with the ratio of ω-3/ω-6 fatty acids, genetic engineering can be used to modify fatty acid metabolism. Synechococcus sp. PCC7002, a fast-growing cyanobacterium, does not contain a Δ6 desaturase gene and is therefore unable to synthesize γ-linolenic acid (GLA) and stearidonic acid (SDA), which are important in human health. In this work, we constructed recombinant vectors Syd6D, Syd15D and Syd6Dd15D to express the Δ15 desaturase and Δ6 desaturase genes from Synechocystis PCC6803 in Synechococcus sp. PCC7002, with the aim of expressing polyunsaturated fatty acids. Overexpression of the Δ15 desaturase gene in Synechococcus resulted in 5.4 times greater accumulation of α-linolenic acid compared with the wild-type while Δ6 desaturase gene expression produced both GLA and SDA. Co-expression of the two genes resulted in low-level accumulation of GLA but much larger amounts of SDA, accounting for as much to 11.64% of the total fatty acid content.

Model of a ternary complex between activated factor VII, tissue factor and factor IX.

PubMed

Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

2002-07-01

Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

[Separation of gamma linolenic acid from evening primrose oil with urea inclusion--orthogonal experiment of optimizing technological parameters and observation of urea inclusion compound I].

PubMed

Wang, Hua; Ling, Man; Xue, Gang; Liu, Fengxia; Guo, Shuxian

2010-05-01

The influence on the urea inclusion compound under different conditions (allocated proportion, time of inclusion, temperature of inclusion) were studied through the orthogonal test, and theoretical reference of urea inclusion process for further optimization wound be offered. The orthogonal experiment was adopted, and microscope was used to observe the shape, aperture size of the urea inclusion compound under different technological parameters, the GC was employed to inspect the purity of GLA. The results indicated that the ratio of fatty acids and urea, inclusion of temperature, time of inclusion had great effect on urea inclusion compound. The three factors and its interactions significantly affected the purity of GLA. The results also showed that the best process was that the ratio of fatty acids and urea was 1 : 3, temperature of inclusion was--15 degrees C, time of inclusion was 24 h. Under the best condition, the purity of GLA reach up to 95.575 9%; and it is feasible to observe the shape and the amount of the urea inclusion compound to reflect and guide the urea inclusion technology.

A stimuli-responsive fluorescence platform for simultaneous determination of d-isoascorbic acid and Tartaric acid based on Maillard reaction product.

PubMed

Zhao, Yanmei; Yuan, Haiyan; Zhang, Xinling; Yang, Jidong

2018-05-05

An activatable fluorescence monitoring platform based on a novel Maillard reaction product from d-glucose and L-arginine was prepared through a facile one-pot approach and applied for simultaneous detection of d-isoascorbic acid and tartaric acid. In this work, the new Maillard reaction product GLA was first obtained, and its fluorescence intensity can be effectively quenched by KMnO 4 , resulting from a new complex (GLA-KMnO 4 ) formation between GLA and KMnO 4 . Upon addition of d-isoascorbic acid or tartaric acid, an enhanced fluorescence was observed under the optimumed experimental conditions, indicating a stimuli-responsive fluorescence turn on platform for d-isoascorbic acid or tartaric acid can be developed. The corresponding experimental results showed that this turn on fluorescence sensing platform has a high sensitivity for d-isoascorbic acid or tartaric acid, because the detection limits were 5.9μM and 21.5μM, respectively. Additionally, this proposed sensing platform was applied to simultaneously detection of d-isoascorbic acid and tartaric acid in real tap water samples with satisfactory results. Copyright © 2018 Elsevier B.V. All rights reserved.

Survey of the total fatty acid and triacylglycerol composition and content of 30 duckweed species and cloning of a Δ6-desaturase responsible for the production of γ-linolenic and stearidonic acids in Lemna gibba

PubMed Central

2013-01-01

Background Duckweeds, i.e., members of the Lemnoideae family, are amongst the smallest aquatic flowering plants. Their high growth rate, aquatic habit and suitability for bio-remediation make them strong candidates for biomass production. Duckweeds have been studied for their potential as feedstocks for bioethanol production; however, less is known about their ability to accumulate reduced carbon as fatty acids (FA) and oil. Results Total FA profiles of thirty duckweed species were analysed to assess the natural diversity within the Lemnoideae. Total FA content varied between 4.6% and 14.2% of dry weight whereas triacylglycerol (TAG) levels varied between 0.02% and 0.15% of dry weight. Three FA, 16:0 (palmitic), 18:2Δ9,12 (Linoleic acid, or LN) and 18:3Δ9,12,15 (α-linolenic acid, or ALA) comprise more than 80% of total duckweed FA. Seven Lemna and two Wolffiela species also accumulate polyunsaturated FA containing Δ6-double bonds, i.e., GLA and SDA. Relative to total FA, TAG is enriched in saturated FA and deficient in polyunsaturated FA, and only five Lemna species accumulate Δ6-FA in their TAG. A putative Δ6-desaturase designated LgDes, with homology to a family of front-end Δ6-FA and Δ8-spingolipid desaturases, was identified in the assembled DNA sequence of Lemna gibba. Expression of a synthetic LgDes gene in Nicotiana benthamiana resulted in the accumulation of GLA and SDA, confirming it specifies a Δ6-desaturase. Conclusions Total accumulation of FA varies three-fold across the 30 species of Lemnoideae surveyed. Nine species contain GLA and SDA which are synthesized by a Δ6 front-end desaturase, but FA composition is otherwise similar. TAG accumulates up to 0.15% of total dry weight, comparable to levels found in the leaves of terrestrial plants. Polyunsaturated FA is underrepresented in TAG, and the Δ6-FA GLA and SDA are found in the TAG of only five of the nine Lemna species that produce them. When present, GLA is enriched and SDA diminished relative to their abundance in the total FA pool. PMID:24308551

Vitamin K Status in Spaceflight and Ground-Based Models of Spaceflight

PubMed Central

Zwart, Sara R; Booth, Sarah L; Peterson, James W; Wang, Zuwei; Smith, Scott M

2011-01-01

Bone loss is a well-documented change during and after long-duration spaceflight. Many types of countermeasures to bone loss have been proposed, including vitamin K supplementation. The objective of this series of studies was to measure change in vitamin K status in response to microgravity under a variety of spaceflight and spaceflight analog (model) conditions, including long-duration spaceflight studies (n = 15), three bed rest studies (n = 15, 49, and 24), and a 14-day saturation dive (n= 6). In crew members who flew 2–6 months on the International Space Station, in-flight and postflight plasma phylloquinone concentrations were unchanged from the preflight mean. Consistent with this finding, urinary γ-carboxyglutamic acid (GLA), a measure of vitamin K-dependent protein turnover, did not change in response to flight. Serum undercarboxylated osteocalcin (%ucOC), a measure of vitamin K function, was generally unchanged in response to flight. Spaceflight findings were corroborated by findings of no changes in phylloquinone, urinary GLA, or %ucOC during or after bed rest in three separate bed rest studies (21–90 days in duration) or after a 14-day saturation dive. The data presented here do not support either a need for vitamin K supplementation during spaceflight or the suggestion of using vitamin K as a bone loss countermeasure in spaceflight. © 2011 American Society for Bone and Mineral Research. PMID:21541997

TLR-adjuvanted nanoparticle vaccines differentially influence the quality and longevity of responses to malaria antigen Pfs25.

PubMed

Thompson, Elizabeth A; Ols, Sebastian; Miura, Kazutoyo; Rausch, Kelly; Narum, David L; Spångberg, Mats; Juraska, Michal; Wille-Reece, Ulrike; Weiner, Amy; Howard, Randall F; Long, Carole A; Duffy, Patrick E; Johnston, Lloyd; O'Neil, Conlin P; Loré, Karin

2018-05-17

Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations of Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, in part due to the poorly immunogenic nature of Pfs25. Using nonhuman primates, we demonstrate that multiple aspects of Pfs25 immunity were enhanced by antigen encapsulation in poly(lactic-co-glycolic acid)-based [(PLGA)-based] synthetic vaccine particles (SVP[Pfs25]) and potent TLR-based adjuvants. SVP[Pfs25] increased Ab titers, Pfs25-specific plasmablasts, circulating memory B cells, and plasma cells in the bone marrow when benchmarked against the clinically tested multimeric form Pfs25-EPA given with GLA-LSQ. SVP[Pfs25] also induced the first reported Pfs25-specific circulating Th1 and Tfh cells to our knowledge. Multivariate correlative analysis indicated several mechanisms for the improved Ab responses. While Pfs25-specific B cells were responsible for increasing Ab titers, T cell responses stimulated increased Ab avidity. The innate immune activation differentially stimulated by the adjuvants revealed a strong correlation between type I IFN polarization, induced by R848 and CpG, and increased Ab half-life and longevity. Collectively, the data identify ways to improve vaccine-induced immunity to poorly immunogenic proteins, both by the choice of antigen and adjuvant formulation, and highlight underlying immunological mechanisms.

Determination of Critical Conditions of Spontaneous Combustion of Coal in Longwall Gob Areas / Wyznaczanie Warunków Krytycznych Samozapalania Węgla W Zrobach Ścian

NASA Astrophysics Data System (ADS)

Cygankiewicz, Janusz

2015-09-01

Decades of experience in the fight against endogenous fire hazard in coal mines indicate a major influence of certain conditions in a given area of the mine on the possibility of fire occurrence, such as: susceptibility of coals to spontaneous combustion, oxygen content in the air incoming to the self-heating coal, conditions of heat exchange between the self-heating coal mass and the environment This paper presents a numerical method for determining the critical conditions of spontaneous combustion of coal in longwall gob areas, i.e. conditions under which spontaneous combustion may occur. It has been assumed that crushed coal in the gob has a shape of a flat layer adjacent from the roof and floor side to the rocks. Our considerations have been limited to coals containing small amount of moisture. A simple model of oxidation kinetics on the coal surface expressed by the Arrhenius equation has been adopted. This model assumes that oxidation rate is independent of the amount of oxygen absorbed by coal. The rate of reaction depends only on temperature, with the parameters of the equation changing after the coal has reached the critical temperature. The article presents also a mathematical model of spontaneous heating of the coal layer in the gob area. It describes the heat balance in the coal as well as the oxygen and heat balance in the flowing gases. The model consists of a system of differential equations which are solved using numerical techniques. The developed computer program enables to perform the relevant calculations. In this paper, on the example of coal from a seam 405, we present the method for determining the following critical parameters of the layer of crushed coal: thickness of the layer, oxygen content in a stream of gases flowing through the layer and thermal conductivity of surrounding rocks. Wieloletnie doświadczenie w zakresie zwalczania zagrożenia pożarem endogenicznym w kopalniach wskazują na zasadniczy wpływ na możliwość zaistnienia pożaru niektórych warunków panujących w danym miejscu kopalni, takich jak: - skłonność węgla do samozapalania - zawartość tlenu w powietrzu dopływającym do zagrzewającego się węgla. W pracy przedstawiono numeryczną metodę wyznaczania warunków krytycznych samozapalania węgla w zrobach ścian, czyli takich po spełnieniu których może dojść do samozapalenia. Przyjęto, że znajdujący się w zrobach rozkruszony węgiel ma kształt płaskiej warstwy, sąsiadującej od stropu i spągu ze skałami. Rozważania ograniczono do węgli charakteryzujących się niską zawartością wilgoci. Przyjęto prosty model kinetyki utleniania na powierzchni węgla wyrażony równaniem Arrheniusa. Model ten zakłada niezależność szybkości utleniania od ilości tlenu pochłoniętego przez węgiel. Szybkość reakcji zależy jedynie od temperatury , przy czym występujące w równaniu parametry zmieniają się po osiągnięciu przez węgiel temperatury krytycznej. W artykule przedstawiono matematyczny model samozagrzewania warstwy węgla w zrobach opisujący bilans ciepła w węglu oraz bilans tlenu i bilans ciepła w przepływających gazach. Tworzące model układy równań różniczkowych cząstkowych rozwiązywane są metodami numerycznymi. Opracowany program komputerowy umożliwia wykonywanie stosownych obliczeń. W pracy, na przykładzie węgla z pokładu 405 , przedstawiono sposób wyznaczania warunków krytycznych warstwy rozkruszonego węgla: grubości warstwy, zawartości tlenu w przepływających przez warstwę gazach oraz przewodności cieplnej otaczających skał.

Application of Relevance Maps in Multidimensional Classification of Coal Types / Zastosowanie Map Odniesienia W Wielowymiarowej Klasyfikacji Typów Węgla

NASA Astrophysics Data System (ADS)

Niedoba, Tomasz

2015-03-01

Multidimensional data visualization methods are a modern tool allowing to classify some analyzed objects. In the case of grained materials e.g. coal, many characteristics have an influence on the material quality. In case of coal, apart from most obvious features like particle size, particle density or ash contents there are many others which cause significant differences between considered types of material. The paper presents the possibility of applying visualization techniques for coal type identification and determination of significant differences between various types of coal. Author decided to apply relevance maps to achieve this purpose. Three types of coal - 31, 34.2 and 35 (according to Polish classification of coal types) were investigated, which were initially screened on sieves and then divided into density fractions. Then, each size-density fraction was chemically analyzed to obtain other characteristics. It was stated that the applied methodology allows to identify certain coal types efficiently and can be used as a qualitative criterion for grained materials. However, it was impossible to achieve such identification comparing all three types of coal together. The presented methodology is new way of analyzing data concerning widely understood mineral processing. Surowce mineralne, które podlegają wzbogacaniu w celu ich lepszego wykorzystania mogą być (charakteryzują się) charakteryzowane wieloma wskaźnikami opisującymi ich, interesujące przeróbkarza, cechy. Podstawowymi cechami są wielkość ziaren oraz ich gęstość, które decydują o przebiegu rozdziału zbiorów ziaren (nadaw) i efektach takiego rozdziału. Rozdział prowadzi się z reguły, w celu uzyskania produktów o zróżnicowanych wartościach średnich wybranej cechy, która zwykle charakteryzowana jest zawartością określonego składnika surowca wyznaczoną na drodze analiz chemicznych. Takie podejście do surowca mineralnego prowadzi do potraktowania go jako wielowymiarowego wektora X = [X1,..., Xn]. Zasadniczym problemem jest także wybór jednostki populacji generalnej (ziarno, jednostka objętości lub masy), co może decydować o kierunkach charakteryzowania wielowymiarowych powiązań cech wektora X. Takimi kierunkami charakteryzowania mogą być: - wielowymiarowe rozkłady wektora losowego X wraz ze wszystkimi konsekwencjami metody (Lyman, 1993; Niedoba, 2009; 2011; Olejnik et al., 2010; Niedoba i Surowiak, 2012); - wielowymiarowe równania regresji wraz z analizą macierzy współczynników korelacji liniowej oraz korelacji cząstkowej (Niedoba, 2013b); - analiza czynnikowa (Tumidajski, 1997; Tumidajski and Saramak, 2009); - metody wielowymiarowej wizualizacji danych. W artykule zastosowano nowoczesną metodę wizualizacji wielowymiarowych danych - metodę tzw. map odniesienia (z ang. relevance maps). Aby zastosować ww. metodę przeprowadzono doświadczenia na trzech typach węgla, pobranych z trzech kopalni węgla kamiennego, zlokalizowanych w Górnośląskim Okręgu Przemysłowym. Były to węgle typu 31, 34.2 i 35, według polskiej klasyfikacji węgli. Każdą z pobranych prób poddano rozdziałowi na klasy ziarnowe a następnie każdą z klas ziarnowych rozdzielono na frakcje densymetryczne za pomocą rozdziału w roztworze chlorku cynku. Tak otrzymane klaso-frakcje przebadano chemiczne ze względu na wybrane parametry jakościowe węgla. Były to takie cechy jak: ciepło spalania, zawartość popiołu, zawartość siarki, zawartość substancji lotnych oraz miąższość materiału. Otrzymano w ten sposób zestaw siedmiu danych dla każdej klasy ziarnowej i każdego typu węgla. Stanowił on swoisty siedmiowymiarowy zbiór, który postanowiono zobrazować za pomocą techniki wizualizacji bazującej na tzw. mapach odniesienia. W metodzie map odniesienia na płaszczyźnie służącej do wizualizacji danych zostają rozmieszczone specjalne punkty zwane punktami odniesienia, reprezentujące poszczególne cechy. Do każdej cechy (współrzędnej) zostaje przyporządkowany punkt odniesienia reprezentujący tą cechę. Czyli przy danych 7-wymiarowych umieszczamy na płaszczyźnie 7 takich punktów odniesienia reprezentujących poszczególne współrzędne. Rozkład punktów reprezentujących przedstawiane wielowymiarowe dane odzwierciedla relacje pomiędzy tymi danymi a cechami. Im bardziej i-ta cecha występuje w danym obiekcie (czyli i-ta współrzędna ma większą wartość), tym bliżej powinien leżeć punkt reprezentujący dany obiekt względem punktu odniesienia reprezentującego i-tą cechę (współrzędną). W ten sposób każdy punkt odniesienia reprezentujący daną cechę, dzieli płaszczyznę na obszary bardziej oraz mniej zależne od cechy nr i (mniej oraz bardziej odległe od punktu odniesienia reprezentującego i-tą cechę). Dokładny opis algorytmu przedstawiono w podrozdziale 3 artykułu. Za pomocą omawianej metody dokonano wizualizacji danych dotyczących przedstawionych typów węgla. Uzyskane rezultaty przedstawiono na rysunkach 1-9. Widoki te pokazują sposób, w jaki 7-wymiarowe dane zostają przekształcone przy pomocy mapy odniesienia do dwóch wymiarów. Algorytm wizualizacji przy użyciu mapy odniesienia działa tak by pomimo znacznej redukcji liczby wymiarów, w jak największym stopniu odległości pomiędzy punktem reprezentującym konkretny wektor danych a punktami odniesienia zależały od współrzędnych tego wektora danych. W ten sposób na ekranie 2-wymiarowym, możemy zobaczyć istotne cechy danych 7-wymiarowych. Na rysunkach 1-4 widać, w jaki sposób wzrasta grupowanie punktów reprezentujących trzy różne klasy węgla (31, 34.2 oraz 35) wraz ze wzrostem parametru ITER. Widać, że punkty będące obrazami danych reprezentujących te same klasy węgla zaczynają zajmować osobne podobszary oraz zaczynają się grupować. Jednak w niektórych częściach przestrzeni obrazy punktów reprezentujących różne klasy węgla zachodzą na siebie. Przez to nie możemy na podstawie tych rysunków stwierdzić, że analizowane dane pozwalają na prawidłową klasyfikację typów węgla. W celu uzyskania bardziej czytelnych wyników postanowiono przedstawić przy pomocy mapy odniesienia, te same dane w nieco inny sposób. Postanowiono przeanalizować dane reprezentujące różne typy węgla parami. Rysunek 5 przedstawia widok uzyskany dla danych reprezentujących typy węgla 34.2 oraz 35. Widać na nim czytelnie, że obrazy punktów reprezentujących próbki węgla typu 34.2 gromadzą się w skupiskach, które łatwo można odseparować od skupisk obrazów punktów reprezentujących próbki węgla 35. Podobne obserwacje dokonano na podstawie rysunków 6 i 7, gdzie przedstawiono parami, odpowiednio, węgle typu 31 i 34.2 oraz 31 i 35. Przeprowadzona wizualizacja wielowymiarowa przy użyciu map odniesienia pozwala więc stwierdzić, że informacje zawarte w analizowanych siedmiowymiarowych danych są wystarczające do prawidłowej klasyfikacji typów węgla 31, 34.2 oraz 35.

Solid-State Lighting Module (SSLM)

NASA Technical Reports Server (NTRS)

2008-01-01

The project's goal was to build a light-emitting-diode (LED)-based light fixture that is identical in fit, form, and function to the existing International Space Station (ISS) General Luminaire Assembly (GLA) light fixture and fly it on the ISS in early FY 2008 as a Station Detailed Test Objective (SDTO). Our design offers the following strengths: proven component hardware: Our design uses components flown in other KSC-developed hardware; heat path thermal pad: LED array heat is transferred from the circuit board by silicon pad, negating the need for a cooling fan; variable colorimetry: The output light color can be changed by inserting different LED combinations.

Expression, purification, immunogenicity and protective efficacy of a recombinant nucleoside hydrolase from Leishmania donovani, a vaccine candidate for preventing cutaneous leishmaniasis.

PubMed

McAtee, C Patrick; Seid, Christopher A; Hammond, Molly; Hudspeth, Elissa; Keegan, Brian P; Liu, Zhuyun; Wei, Junfei; Zhan, Bin; Arjona-Sabido, Raul; Cruz-Chan, Vladimir; Dumonteil, Eric; Hotez, Peter J; Bottazzi, Maria Elena

2017-02-01

The nucleoside hydrolase gene from Leishmania donovani was cloned and expressed in Escherichia coli as a full length 36-kDa protein (LdNH36). Following lysis and extraction, the protein was purified by anion exchange and gel filtration chromatography. The purified protein had a molecular mass of approximately 36-kDa and was confirmed to be >99% pure. Using a nucleoside hydrolase assay, the protein was found to exhibit a Km of 741 ± 246 μM. Protein integrity was confirmed by lithium dodecyl sulfate polyacrylamide gel electrophoresis (LDS-PAGE), mass spectrometry (MS), and enzymatic assay. Analysis of antibody levels from immunized mice indicated that LdNH36 alone or in a stable emulsion with the Toll-like receptor-4 ligand glucopyranosyl lipid adjuvant (GLA-SE) as immunostimulant induced high levels of antigen-specific IgG antibodies. The cellular immune response indicated a T h 1 response in mice immunized with LdNH36, but only when formulated with GLA-SE. Mice immunized with the LdNH36 antigen in combination with the GLA-SE adjuvant and challenged with Leishmania mexicana showed significant reductions (>20 fold) in parasite burden, confirming the protective efficacy of this vaccine candidate. Copyright © 2016 Elsevier Inc. All rights reserved.

Ammonia activates pacC and patulin accumulation in an acidic environment during apple colonization by Penicillium expansum.

PubMed

Barad, Shiri; Espeso, Eduardo A; Sherman, Amir; Prusky, Dov

2016-06-01

Penicillium expansum, the causal agent of blue mould rot, causes severe post-harvest fruit maceration simultaneously with the secretion of d-gluconic acid (GLA) and the mycotoxin patulin in colonized tissue. The factor(s) inducing patulin biosynthesis during colonization of the host acidic environment is unclear. During the colonization of apple fruit in vivo and growth in culture, P. expansum secretes pH-modulating GLA and ammonia. Although patulin and its possible opportunistic precursor GLA accumulate together during fungal development, ammonia is detected on the colonized tissue's leading edge and after extended culture, close to patulin accumulation. Here, we demonstrate ammonia-induced transcript activation of the global pH modulator PacC and patulin accumulation in the presence of GLA by: (i) direct exogenous treatment of P. expansum growing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self-ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the patulin biosynthesis cluster. Ammonia induced patulin accumulation concurrently with the transcript activation of pacC and patulin biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacC transcript expression under acidic conditions. Electrophoretic mobility shift assays using P. expansum PacC and antibodies to the different cleaved proteins showed that PacC is not protected against proteolytic signalling at pH 4.5 relative to pH 7.0, but NH4 addition did not further enhance its proteolytic cleavage. Ammonia enhanced the activation of palF transcript in the Pal pathway under acidic conditions. Ammonia accumulation in the host environment by the pathogen under acidic pH may be a regulatory cue for pacC activation, towards the accumulation of secondary metabolites, such as patulin. © 2015 BSPP AND JOHN WILEY & SONS LTD.

In vivo estrogenic-like activities of Gouania longipetala Hemsl. (Rhamnaceae) bark extracts in a post-menopause-like model of ovariectomized Wistar rats.

PubMed

Paul Désiré, Dzeufiet Djomeni; Yolande Sandrine, Mengue Ngadena; Danielle Claude, Bilanda; Mireille, Kameni; Oumarou Bibi-Farouck, Aboubakar; Théophile, Dimo; Pierre, Kamtchouing

2015-06-20

Gouania longipetala is commonly used in Cameroonian traditional medicine to manage women fertility and menopausal complaints. However, despite this use, the estrogenic properties of G. longipetala have not been studied until now. The present study was aimed to assess estrogenic activities of the stem bark aqueous (GLA) and ethanolic (GLE) extracts of G. longipetala in post-menopause-like model of ovariectomized (Ovx) Wistar rats. Animals were either sham-operated or Ovx. 84 days after ovariectomy, animals were divided into seven groups of five animals and were daily treated for 28 days with distilled water (10 mL/kg) for group 1, 2% solution of Tween 80 (10 mL/kg) for group 2, estradiol valerate (1 mg/kg) for group 3, GLA (45 or 180 mg/kg) and GLE (40 or 160 mg/kg) for groups 4 to 7 respectively. Sham-operated animals daily received distilled water (10 mL/kg). During the experimental period, the body weight was registered every week. At the day 29, blood pressure was registered by invasive method while uterine and vagina morphometry as well as body, uterine and abdominal fat weights changes were analyzed. Serum levels of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were determined. Moreover, oxidative stress markers such as nitrites, reduced glutathione (GSH) and malondialdehyde (MDA) were measured in homogenized liver and aorta. Compared with the sham control, vagina and uterine dystrophy and elevated blood pressure were observed in Ovx rats treated with vehicles. Biochemical parameters showed a significant increase of total cholesterol, triglycerides, LDL-cholesterol and MDA as well as a significant decrease of nitrites and GSH in Ovx animals treated with vehicle as compared to sham group. GLA and GLE displayed estrogen-like effects on vagina and did not affect uterine wet weight and epithelial height compared with vehicle groups. Both extracts displayed anti-atherogenic properties by reducing AI, AIP and LDL-cholesterol level as compared to vehicles groups. GLA and GLE significantly prevented the increase of MDA induced by ovariectomy as compared to rats treated with vehicles. This study showed that GLA and GLE exhibited estrogenic effects by providing vaginal lubrication, by modulating blood pressure and improving lipid profile, oxidative status and endothelial function and may not have an undesirable influence on the endometrium in ovariectomized rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Significant improvement in Fabry disease podocytopathy after 3 years of treatment with agalsidase beta.

PubMed

Ito, Shuichi; Ogura, Masao; Kamei, Koichi; Matsuoka, Kentaro; Warnock, David G

2016-08-01

Fabry disease is an X-linked lysosomal disorder caused by decreased activity of α-galactosidase A (GLA). Consequent accumulation of globotriaosylceramide (GL-3) in lysosomes results in damage to a variety of organs, including the kidneys. Enzyme replacement therapy (ERT) is an effective treatment, but whether it should be started before organ damage is evident is a matter of debate. A 10-year-old boy who complained of severe sole pain for 3 years had been misdiagnosed with juvenile idiopathic arthritis. Further investigations revealed decreased GLA activity and a M1T mutation in the GLA gene causing protein truncation, suggestive of Fabry disease. Despite normal renal function and urinalysis, renal biopsy showed abnormal structure, with marked accumulation of GL-3 in podocytes, partial effacement of foot processes and irregularly reduced expression of nephrin in the slit diaphragm. After 1 year of ERT with 1 mg/kg agalsidase beta once every 2 weeks, his pain had resolved with ERT combined with carbamazepine and pregabalin. After 3 years of the ERT, repeat biopsy showed little renal GL-3 deposition, resolution of foot process effacement, and a dramatic improvement in nephrin expression. There may be a window of opportunity in which pain and renal injury can be addressed in the early stages of Fabry disease. Early initiation of ERT should therefore be considered for children with Fabry disease.

Structure and dynamics of zymogen human blood coagulation factor X.

PubMed

Venkateswarlu, Divi; Perera, Lalith; Darden, Tom; Pedersen, Lee G

2002-03-01

The solution structure and dynamics of the human coagulation factor X (FX) have been investigated to understand the key structural elements in the zymogenic form that participates in the activation process. The model was constructed based on the 2.3-A-resolution x-ray crystallographic structure of active-site inhibited human FXa (PDB:1XKA). The missing gamma-carboxyglutamic acid (GLA) and part of epidermal growth factor 1 (EGF1) domains of the light chain were modeled based on the template of GLA-EGF1 domains of the tissue factor (TF)-bound FVIIa structure (PDB:1DAN). The activation peptide and other missing segments of FX were introduced using homology modeling. The full calcium-bound model of FX was subjected to 6.2 ns of molecular dynamics simulation in aqueous medium using the AMBER6.0 package. We observed significant reorientation of the serine-protease (SP) domain upon activation leading to a compact multi-domain structure. The solution structure of zymogen appears to be in a well-extended conformation with the distance between the calcium ions in the GLA domain and the catalytic residues estimated to be approximately 95 A in contrast to approximately 83 A in the activated form. The latter is in close agreement with fluorescence studies on FXa. The S1-specificity residues near the catalytic triad show significant differences between the zymogen and activated structures.

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

PubMed Central

Ferreira, Susana; Auray-Blais, Christiane; Boutin, Michel; Lavoie, Pamela; Nunes, José Pedro; Martins, Elisabete; Garman, Scott; Oliveira, João Paulo

2016-01-01

Recent data have shown that lyso-Gb3, the deacylated derivative of globotriaosylceramide (Gb3), is possibly involved in the pathogenesis of Fabry disease (FD) and might be a clinically useful biomarker of its metabolic load. To test this hypothesis, we assayed Gb3 and lyso-Gb3 and related analogs in plasma and/or urine samples of 12 clinically well-characterized subjects carrying several different GLA variant alleles associated with a wide range of residual α-galactosidase A activities. Urinary Gb3 was measured by HPLC–MS/MS; plasma and urinary lyso-Gb3 and related analogs were measured by UPLC–MS/MS. Individual profiles of Gb3 and lyso-Gb3 and related analogs closely correlated with the phenotypic data for each subject, discerning the classical FD patient from the two patients carrying cardiac variants as well as these from all the others without FD. The lyso-Gb3 analog at m/z 836 was found at increased levels only in patients manifesting clinically severe heart disease, irrespective of the pathogenicity of the GLA variant they carried. This finding suggests that this lyso-Gb3 analog might be an earlier biomarker of progressive heart disease, non-specific of the FD cardiomyopathy. The possibility that urinary Gb3 is a specific marker of kidney involvement in FD deserves further study. PMID:26070511

The analysis sensitivity to tropical winds from the Global Weather Experiment

NASA Technical Reports Server (NTRS)

Paegle, J.; Paegle, J. N.; Baker, W. E.

1986-01-01

The global scale divergent and rotational flow components of the Global Weather Experiment (GWE) are diagnosed from three different analyses of the data. The rotational flow shows closer agreement between the analyses than does the divergent flow. Although the major outflow and inflow centers are similarly placed in all analyses, the global kinetic energy of the divergent wind varies by about a factor of 2 between different analyses while the global kinetic energy of the rotational wind varies by only about 10 percent between the analyses. A series of real data assimilation experiments has been performed with the GLA general circulation model using different amounts of tropical wind data during the First Special Observing Period of the Global Weather Experiment. In exeriment 1, all available tropical wind data were used; in the second experiment, tropical wind data were suppressed; while, in the third and fourth experiments, only tropical wind data with westerly and easterly components, respectively, were assimilated. The rotational wind appears to be more sensitive to the presence or absence of tropical wind data than the divergent wind. It appears that the model, given only extratropical observations, generates excessively strong upper tropospheric westerlies. These biases are sufficiently pronounced to amplify the globally integrated rotational flow kinetic energy by about 10 percent and the global divergent flow kinetic energy by about a factor of 2. Including only easterly wind data in the tropics is more effective in controlling the model error than including only westerly wind data. This conclusion is especially noteworthy because approximately twice as many upper tropospheric westerly winds were available in these cases as easterly winds.

Cellular Localization and Characterization of Cytosolic Binding Partners for Gla Domain-containing Proteins PRRG4 and PRRG2*

PubMed Central

Yazicioglu, Mustafa N.; Monaldini, Luca; Chu, Kirk; Khazi, Fayaz R.; Murphy, Samuel L.; Huang, Heshu; Margaritis, Paris; High, Katherine A.

2013-01-01

The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins. PMID:23873930

Rare Earth Elements of Orzeskie Beds of South-West Part Upper Silesian Coal Basin (Poland) / Pierwiastki Ziem Rzadkich Z Pokładów Węgla Warstw Orzeskich Południowo-Zachodniej Części Gzw (Polska)

NASA Astrophysics Data System (ADS)

Adamczyk, Zdzisław; Białecka, Barbara; Moszko, Joanna Całusz; Komorek, Joanna; Lewandowska, Małgorzata

2015-03-01

The subject of the research concerned the coal samples from 360/1, 361 and 362/1 seams of the Orzesze beds in the "Pniówek" coal mine. The obtained samples were characterized by low ash content - 2.22- 6.27% of the mass. The chemical composition of the ash indicates the presence of aluminosilicate minerals in the analyzed coal samples - most likely clay minerals, the presence of which has been confirmed in microscopic tests of the petrographic composition of channel samples of coal. The content of rare earth elements (REE sum) in the ash of the tested coal seams ranged from 364 to 1429 ppm. Variation of the REE content has been observed within a single seam. The fraction of REE indicates a relation with a mineral substance. No relation of the REE fraction and the presence of red beds has been found based on the tested samples. The content of REE found in ash, normalized to chondrites, is characterized by LREE enrichment in relation to HREE. The Eu anomaly is most likely related to tuff and tonstein levels occurring in Orzesze beds, which accompany the coal seams in the Upper Silesian Coal Basin (i.a., south of the studied area). The research has indicated that LREE in the tested samples are more related to the mineral substance, while HREE have a stronger affinity with organic substances. Przedmiotem badań były próbki węgla z pokładów 360/1, 361 i 362/1 warstw orzeskich KWK Pniówek. Próbki te charakteryzują się niewielką zawartością popiołu 2,22-6,27% mas. Skład chemiczny popiołów wskazuje na obecność w analizowanych próbkach węgla minerałów z grupy glinokrzemianów najprawdopodobniej minerałów ilastych, których obecność była stwierdzona w badaniach mikroskopowych składu petrograficznego próbek bruzdowych węgla. Zawartości pierwiastków ziem rzadkich (suma REE) w popiołach badanych pokładów węgla wahają się od 364 do 1429 ppm. Obserwuje się zróżnicowanie zawartości REE w obrębie jednego pokładu. Udział REE wykazuje związek z substancją mineralną. Nie stwierdzono związku udziału REE, w badanych próbkach, z obecnością utworów pstrych w stropie karbonu. Zawartości REE oznaczone w popiołach, znormalizowane do chondrytów, charakteryzują się wzbogaceniem LREE wobec HREE. Anomalia Eu związana jest prawdopodobnie z występującymi w warstwach orzeskich (m.in. na północ od obszaru badań) Górnośląskiego Zagłębia Węglowego poziomami tufów i tonsteinów, które towarzyszą pokładom węgla. Badania wykazały, że LREE w badanych próbkach związane są raczej z substancją mineralną, natomiast HREE posiadają silniejsze powinowactwo z substancją organiczną.

Canola and hydrogenated soybean oils accelerate ectopic bone formation induced by implantation of bone morphogenetic protein in mice.

PubMed

Hashimoto, Yoko; Mori, Mayumi; Kobayashi, Shuichiro; Hanya, Akira; Watanabe, Shin-Ichi; Ohara, Naoki; Noguchi, Toshihide; Kawai, Tatsushi; Okuyama, Harumi

2014-01-01

Canola oil (Can) and hydrogenated soybean oil (H2-Soy) are commonly used edible oils. However, in contrast to soybean oil (Soy), they shorten the survival of stroke-prone spontaneously hypertensive (SHRSP) rats. It has been proposed that the adverse effects of these oils on the kidney and testis are caused at least in part by dihydro-vitamin K (VK) 1 in H2-Soy and unidentified component(s) in Can. Increased intake of dihydro-VK1 is associated with decreased tissue VK2 levels and bone mineral density in rats and humans, respectively. The aim of the present study was to determine the effects of these oils on bone morphogenetic protein (BMP)-induced ectopic bone formation, which is promoted by VK2 deficiency, in relation to the role of VK in the γ-carboxylation of osteocalcin and matrix Gla protein. A crude extract of BMPs was implanted into a gap in the fascia of the femoral muscle in 5-week-old mice maintained on a Soy, Can, or H2-Soy diet. Newly formed bone volume, assessed by three-dimensional X-ray micro-computed tomography and three-dimensional reconstruction imaging for bone, was 4-fold greater in the Can and H2-Soy groups than in the Soy group. The plasma carboxylated osteocalcin (Gla-OC) and total OC (Gla-OC plus undercarboxylated osteocalcin [Glu-OC]) levels were significantly lower in the Can group than in the Soy group ( p < 0.05). However, these levels did not significantly differ between the H2-Soy and Soy groups. The plasma Gla-OC/Glu-OC ratio in the Can and H2-Soy groups was significantly lower (in Can; p = 0.044) or was almost significantly lower (in H2-Soy; p = 0.053) than that in the Soy group. In conclusion, Can and H2-Soy accelerated BMP-induced bone formation in mice to a greater extent than Soy. Further research is required to evaluate whether the difference in accelerated ectopic bone formation is associated with altered levels of VK2 and VK-dependent protein(s) among the three dietary groups.

River gradient anomalies reveal recent tectonic movements when assuming an exponential gradient decrease along a river course

NASA Astrophysics Data System (ADS)

Žibret, Gorazd; Žibret, Lea

2017-03-01

High resolution digital models, combined with GIS or other terrain modelling software, allow many new possibilities in geoscience. In this paper we develop, describe and test a novel method, the GLA method, to detect active tectonic uplift or subsidence along river courses. It is a modification of Hack's SL-index method in order to overcome the disadvantages of the latter. The core assumption of the GLA method is that over geological time river profiles quickly adjust to follow an exponential decrease in elevation along the river course. Any large deviation can be attributed to active tectonic movement, or to disturbances in erosion/sedimentation processes caused by an anthropogenic structure (e.g. artificial dam). During the testing phase, the locations of identified deviations were compared to the locations of faults, identified on a 1:100,000 geological map. Results show that higher magnitude deviations are found within a maximum radius of 200 m from the fault, and the majority of detected deviations within a maximum radius of 600 m from faults or thrusts. However, these results are not the best that could be obtained because the geological map that was used (and the only one available for the area) is not of the appropriate scale, and was therefore not precise enough. Comparison of deviation magnitudes against PSInSAR measurements of vertical displacements in the vicinity revealed that in spite of the very few suitable points available, a good correlation between both independent methods was obtained (R2 = 0.68 for the E research area and R2 = 0.69 for the W research area). The GLA method was applied to the three test sites where previous studies have shown active tectonic movements. It shows that deviations occur at the intersections between active faults and river courses, as well as also correctly detected active uplift, attributed to the increased sedimentation rate above an artificial hydropower dam, and an increased erosion rate below. The method gives promising results, and it is acknowledged that the GLA method needs to be tested in other locations around the world.

On the distance of genetic relationships and the accuracy of genomic prediction in pig breeding.

PubMed

Meuwissen, Theo H E; Odegard, Jorgen; Andersen-Ranberg, Ina; Grindflek, Eli

2014-08-01

With the advent of genomic selection, alternative relationship matrices are used in animal breeding, which vary in their coverage of distant relationships due to old common ancestors. Relationships based on pedigree (A) and linkage analysis (GLA) cover only recent relationships because of the limited depth of the known pedigree. Relationships based on identity-by-state (G) include relationships up to the age of the SNP (single nucleotide polymorphism) mutations. We hypothesised that the latter relationships were too old, since QTL (quantitative trait locus) mutations for traits under selection were probably more recent than the SNPs on a chip, which are typically selected for high minor allele frequency. In addition, A and GLA relationships are too recent to cover genetic differences accurately. Thus, we devised a relationship matrix that considered intermediate-aged relationships and compared all these relationship matrices for their accuracy of genomic prediction in a pig breeding situation. Haplotypes were constructed and used to build a haplotype-based relationship matrix (GH), which considers more intermediate-aged relationships, since haplotypes recombine more quickly than SNPs mutate. Dense genotypes (38 453 SNPs) on 3250 elite breeding pigs were combined with phenotypes for growth rate (2668 records), lean meat percentage (2618), weight at three weeks of age (7387) and number of teats (5851) to estimate breeding values for all animals in the pedigree (8187 animals) using the aforementioned relationship matrices. Phenotypes on the youngest 424 to 486 animals were masked and predicted in order to assess the accuracy of the alternative genomic predictions. Correlations between the relationships and regressions of older on younger relationships revealed that the age of the relationships increased in the order A, GLA, GH and G. Use of genomic relationship matrices yielded significantly higher prediction accuracies than A. GH and G, differed not significantly, but were significantly more accurate than GLA. Our hypothesis that intermediate-aged relationships yield more accurate genomic predictions than G was confirmed for two of four traits, but these results were not statistically significant. Use of estimated genotype probabilities for ungenotyped animals proved to be an efficient method to include the phenotypes of ungenotyped animals.

Parameterization of turbulence and the planetary boundary layer in the GLA Fourth Order GCM

NASA Technical Reports Server (NTRS)

Helfand, H. M.

1985-01-01

A new scheme has been developed to model the planetary boundary layer in the GLAS Fourth Order GCM through explicit resolution of its vertical structure into two or more vertical layers. This involves packing the lowest layers of the GCM close to the ground and developing new parameterization schemes that can express the turbulent vertical fluxes of heat, momentum and moisture at the earth's surface and between the layers that are contained with the PBL region. Offline experiments indicate that the combination of the modified level 2.5 second-order turbulent closure scheme and the 'extended surface layer' similarity scheme should work well to simulate the behavior of the turbulent PBL even at the coarsest vertical resolution with which such schemes will conceivably be used in the GLA Fourth Order GCM.

Clinical Benefits of n-3 PUFA and ɤ-Linolenic Acid in Patients with Rheumatoid Arthritis.

PubMed

Veselinovic, Mirjana; Vasiljevic, Dragan; Vucic, Vesna; Arsic, Aleksandra; Petrovic, Snjezana; Tomic-Lucic, Aleksandra; Savic, Maja; Zivanovic, Sandra; Stojic, Vladislava; Jakovljevic, Vladimir

2017-03-25

(1) Background: Marine n -3 polyunsaturated fatty acids (PUFA) and ɤ-linolenic acid (GLA) are well-known anti-inflammatory agents that may help in the treatment of inflammatory disorders. Their effects were examined in patients with rheumatoid arthritis; (2) Methods: Sixty patients with active rheumatoid arthritis were involved in a prospective, randomized trial of a 12 week supplementation with fish oil (group I), fish oil with primrose evening oil (group II), or with no supplementation (group III). Clinical and laboratory evaluations were done at the beginning and at the end of the study; (3) Results: The Disease Activity Score 28 (DAS 28 score), number of tender joints and visual analogue scale (VAS) score decreased notably after supplementation in groups I and II ( p < 0.001). In plasma phospholipids the n -6/ n -3 fatty acids ratio declined from 15.47 ± 5.51 to 10.62 ± 5.07 ( p = 0.005), and from 18.15 ± 5.04 to 13.50 ± 4.81 ( p = 0.005) in groups I and II respectively. The combination of n -3 PUFA and GLA (group II) increased ɤ-linolenic acid (0.00 ± 0.00 to 0.13 ± 0.11, p < 0.001), which was undetectable in all groups before the treatments; (4) Conclusion: Daily supplementation with n -3 fatty acids alone or in combination with GLA exerted significant clinical benefits and certain changes in disease activity.

Globotriaosylceramide induces lysosomal degradation of endothelial KCa3.1 in fabry disease.

PubMed

Choi, Shinkyu; Kim, Ji Aee; Na, Hye-Young; Cho, Sung-Eun; Park, Seonghee; Jung, Sung-Chul; Suh, Suk Hyo

2014-01-01

Globotriaosylceramide (Gb3) induces KCa3.1 downregulation in Fabry disease (FD). We investigated whether Gb3 induces KCa3.1 endocytosis and degradation. KCa3.1, especially plasma membrane-localized KCa3.1, was downregulated in both Gb3-treated mouse aortic endothelial cells (MAECs) and human umbilical vein endothelial cells. Gb3-induced KCa3.1 downregulation was prevented by lysosomal inhibitors but not by a proteosomal inhibitor. Endoplasmic reticulum stress-inducing agents did not induce KCa3.1 downregulation. Gb3 upregulated the protein levels of early endosome antigen 1 and lysosomal-associated membrane protein 2 in MAECs. Compared with MAECs from age-matched wild-type mice, those from aged α-galactosidase A (Gla)-knockout mice, an animal model of FD, showed downregulated KCa3.1 expression and upregulated early endosome antigen 1 and lysosomal-associated membrane protein 2 expression. In contrast, no significant difference was found in early endosome antigen 1 and lysosomal-associated membrane protein 2 expression between young Gla-knockout and wild-type MAECs. In aged Gla-knockout MAECs, clathrin was translocated close to the cell border and clathrin knockdown recovered KCa3.1 expression. Rab5, an effector of early endosome antigen 1, was upregulated, and Rab5 knockdown restored KCa3.1 expression, the current, and endothelium-dependent relaxation. -Gb3 accelerates the endocytosis and lysosomal degradation of endothelial KCa3.1 via a clathrin-dependent process, leading to endothelial dysfunction in FD.

Characterization of amylolytic enzyme overproducing mutant of Aspergillus luchuensis obtained by ion beam mutagenesis.

PubMed

Kojo, Toshihiro; Kadooka, Chihiro; Komohara, Marisa; Onitsuka, Shiori; Tanimura, Miya; Muroi, Yukiko; Kurazono, Shugo; Shiraishi, Yohei; Oda, Ken; Iwashita, Kazuhiro; Onoue, Masahira; Okutsu, Kayu; Yoshizaki, Yumiko; Takamine, Kazunori; Futagami, Taiki; Mori, Kazuki; Tamaki, Hisanori

2018-01-15

Aspergillus luchuensis is a kuro (black) koji fungus that has been used as a starch degrader for the awamori- and shochu-making industries in Japan. In this study, we investigated the effect of ion beam irradiation on A. luchuensis RIB2601 and obtained a high starch-degrading mutant strain U1. Strain U1 showed reduced growth rate, whereas it showed higher α-amylase, glucoamylase, and α-glucosidase activities on a mycelial mass basis than the wild type (wt) strain both on agar plates and in rice koji. In addition, strain U1 showed higher N-acetylglucosamine content in the cell wall and higher sensitivity to calcofluor white, suggesting a deficiency in cell wall composition. Interestingly, produced protein showed higher expression of acid-labile α-amylase (AmyA) and glucoamylase (GlaA) in strain U1, although real-time RT-PCR indicated no significant change in the transcription of the amyA or glaA gene. These results suggested that the high amylolytic activity of strain U1 is attributable to a high AmyA and GlaA production level, but the elevated production is not due to transcriptional regulation of the corresponding genes. Furthermore, RNA-seq analysis indicated that strain U1 shows transcriptional changes in at least 604 genes related to oxidation-reduction, transport, and glucosamine-containing compound metabolic processes, which may be involved in the deficient cell wall composition of strain U1.

Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum

PubMed Central

Brampton, Christopher; Yamaguchi, Yukiko; Vanakker, Olivier; Laer, Lut Van; Chen, Li-Hsieh; Thakore, Manoj; De Paepe, Anne; Pomozi, Viola; Szabó, Pál T; Martin, Ludovic; Váradi, András

2011-01-01

Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by calcified elastic fibers in cutaneous, ocular and vascular tissues. PXE is caused by mutations in ABCC6, which encodes a protein of the ATP-driven organic anion transporter family. The inability of this transporter to secrete its substrate into the circulation is the likely cause of PXE. Vitamin K plays a role in the regulation of mineralization processes as a co-factor in the carboxylation of calcification inhibitors such as Matrix Gla Protein (MGP). Vitamin K precursor or a conjugated form has been proposed as potential substrate(s) for ABCC6. We investigated whether an enriched diet of vitamin K1 or vitamin K2 (MK4) could stop or slow the disease progression in Abcc6-/- mice. Abcc6-/- mice were placed on a diet of either vitamin K1 or MK4 at 5 or 100 mg/kg at prenatal, 3 weeks or 3 months of age. Disease progression was quantified by measuring the calcium content of one side of the mouse muzzle skin and histological staining for calcium of the opposing side. Raising the vitamin K1 or MK4 content of the diet increased the concentration of circulating MK4 in the serum. However, this increase did not significantly affect the MGP carboxylation status or reduce its abnormal abundance, the total calcium content or the pathologic calcification in the whiskers of the 3 treatment groups compared to controls. Our findings showed that raising the dietary intake of vitamin K1 or MK4 was not beneficial in the treatment of PXE and suggested that the availability of vitamin K may not be a limiting factor in this pathology. PMID:21597330

A fungal biofilm reactor based on metal structured packing improves the quality of a Gla::GFP fusion protein produced by Aspergillus oryzae.

PubMed

Zune, Q; Delepierre, A; Gofflot, S; Bauwens, J; Twizere, J C; Punt, P J; Francis, F; Toye, D; Bawin, T; Delvigne, F

2015-08-01

Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-state-related physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilm reactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae. The biofilm reactor comprises a metal structured packing allowing the attachment of the fungal biomass. Since the production of the target protein is under the control of the promoter glaB, specifically induced in solid-state fermentation, the biofilm mode of culture is expected to enhance the global productivity. Although production of the target protein was enhanced by using the biofilm mode of culture, we also found that fusion protein production is also significant when the submerged mode of culture is used. This result is related to high shear stress leading to biomass autolysis and leakage of intracellular fusion protein into the extracellular medium. Moreover, 2-D gel electrophoresis highlights the preservation of fusion protein integrity produced in biofilm conditions. Two fungal biofilm reactor designs were then investigated further, i.e. with full immersion of the packing or with medium recirculation on the packing, and the scale-up potentialities were evaluated. In this context, it has been shown that full immersion of the metal packing in the liquid medium during cultivation allows for a uniform colonization of the packing by the fungal biomass and leads to a better quality of the fusion protein.

Matrix-Gla Protein rs4236 [A/G] gene polymorphism and serum and GCF levels of MGP in patients with subgingival dental calculus.

PubMed

Doğan, Gülnihal Emrem; Demir, Turgut; Aksoy, Hülya; Sağlam, Ebru; Laloğlu, Esra; Yildirim, Abdulkadir

2016-10-01

Matrix-Gla Protein (MGP) is one of the major Gla-containing protein associated with calcification process. It also has a high affinity for Ca 2+ and hydroxyapatite. In this study we aimed to evaluate the MGP rs4236 [A/G] gene polymorphism in association with subgingival dental calculus. Also a possible relationship between MGP gene polymorphism and serum and GCF levels of MGP were examined. MGP rs4236 [A/G] gene polymorphism was investigated in 110 patients with or without subgingival dental calculus, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. Additionally, serum and GCF levels of MGP of the patients were compared according to subgingival dental calculus. Comparison of patients with and without subgingival dental calculus showed no statistically significant difference in MGP rs4236 [A/G] gene polymorphism (p=0.368). MGP concentrations in GCF of patients with subgingival dental calculus were statistically higher than those without subgingival dental calculus (p=0.032). However, a significant association was not observed between the genotypes of AA, AG and GG of the MGP rs4236 gene and the serum and GCF concentrations of MGP in subjects. In this study, it was found that MGP rs4236 [A/G] gene polymorphism was not to be associated with subgingival dental calculus. Also, that GCF MGP levels were detected higher in patients with subgingival dental calculus than those without subgingival dental calculus independently of polymorphism, may be the effect of adaptive mechanism to inhibit calculus formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between polyunsaturated fatty acid levels in maternal diets and human milk in the first month post-partum.

PubMed

Liu, G; Ding, Z; Li, X; Chen, X; Wu, Y; Xie, L

2016-08-01

The present study evaluated the relationship between dietary fatty acid (FA) intakes and human milk FA levels. Healthy lactating women (n = 514) from Northern China participated in the study. Dietary intake was assessed with a 24-h dietary recall questionnaire and evaluated using golden key maternal nutrition software (Wincome, Shanghai, China) and China Food Composition 2009. Human milk FA composition was determined by gas chromatography. The maternal daily median intakes of linoleic acid (LA), α-linolenic acid (ALA) and arachidonic acid (AA) were 19.93 g, 3.08 g and 16.33 mg, respectively. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were below the recommended levels. FA levels in 100 g of human milk were 0.363 g LA, 0.038 g γ-linolenic acid (GLA), 0.052 g dihomo γ-linolenic acid (DGLA), 0.144 g ALA, 0.079 g AA, 0.007 g EPA, 0.018 g docosatetraenoic acid (DTA) and 0.048 g DHA. Multiple linear regression analysis revealed that human milk DGLA levels were negatively correlated with dietary LA intake (β = -0.223, P = 0.030), and human milk GLA and DTA levels were negatively correlated with dietary ALA intake (β = -2.189, P = 0.031; β = -2.252, P = 0.027) after adjusting for possible confounding factors. The results of the present study suggest the presence of competitive interactions between n-3 fatty acids (ALA) and n-6 fatty acids (GLA and DTA). © 2015 The British Dietetic Association Ltd.

Application of Multidimensional Data Visualization by Means of Self-Organizing Kohonen Maps to Evaluate Classification Possibilities of Various Coal Types / Zastosowanie Wizualizacji Wielowymiarowych Danych Za Pomocą Sieci Kohonena Do Oceny Możliwości Klasyfikacji Różnych Typów Węgla

NASA Astrophysics Data System (ADS)

Jamróz, Dariusz; Niedoba, Tomasz

2015-03-01

Multidimensional data visualization methods are a modern tool allowing to classify some analysed objects. In the case of grained materials e.g. coal, many characteristics have an influence on the material quality. The paper presents the possibility of applying visualization techniques for coal type identification and determination of significant differences between various types of coal. To achieve this purpose, the method of Kohonen maps was applied by means of which three types of coal - 31, 34.2 and 35 (according to Polish classification of coal types) were investigated. It was stated that the applied methodology allows to identify certain coal types efficiently and can be used as a qualitative criterion for grained materials. Metody wizualizacji wielowymiarowych danych są nowoczesnym narzędziem umożliwającym klasyfikację analizowanych obiektów, którymi mogą być różnego typu dane opisujące wybrane zjawisko lub materiał. W przypadku materiałów uziarnionych, jakim jest np. węgiel, wiele cech ma wpływ na jakość materiału, tj. np. gęstość, wielkość ziaren, ciepło spalania, zawartość popiołu, zawartość siarki itp. Na potrzeby artykułu przeprowadzono rozdział węgli z trzech wybranych kopalni węgla kamiennego, zlokalizowanych w Górnośląskim Okręgu Przemysłowym. Każda z tych kopalni pracuje na innego typu węglu. W tym przypadku były to węgle o typach 31, 34.2 oraz 35 (według polskiej klasyfikacji typów węgla). Najpierw, materiał został podzielony na klasy ziarnowe a następnie za pomocą rozdziale w cieczy ciężkiej (roztwór chlorku cynku) na frakcje gęstościowe. Dla tak przygotowanego materiału przeprowadzono następnie analizy chemiczne mające na celu określenie takich parametrów, jak zawartość siarki, zawartość popiołu, zawartość części lotnych, ciepło spalania oraz wilgotność analityczną. W ten sposób, dla każdej klaso-frakcji uzyskano bogate charakterystyki badanego materiału. Nasuwa się więc pytanie, czy możliwa jest identyfikacja typu węgla za pomocą dostępnych danych. W tym celu zastosowano wielowymiarową technikę wizualizacji statystycznej. Istnieje wiele metod takiej wizualizacji, z których kilka było już przedmiotem wcześniejszych publikacji autorów. W tym wypadku autorzy zdecydowali się zastosować metodę sieci Kohonena. Metoda ta została opisana w rozdziale 2 pracy, gdzie oprócz opisu teoretycznego podano również główne wzory stosowane podczas modelowania tą metodą (wzory (1)-(5)). Do zbadania postawionego problemu wykorzystano optymalną liczbę iteracji i optymalny czas uczenia sieci. Pewnym problemem pojawiającym się przy takiej wizualizacji jest konieczność doboru parametrów, w celu uzyskania widoku, który w sposób czytelny prezentuje poszukiwane przez nas informacje. Należy wspomnieć, że w trakcie prowadzonych eksperymentów uzyskiwano widoki przy użyciu sieci neuronowej o wielkości od 10 × 10 do 100 × 100 neuronów. Widoki były uzyskiwane przy wartości parametru MAX_DISTANCE od 1 do wielkości sieci oraz parametru ITER od 1 do 5000. Eksperymenty były prowadzone dla różnych wzorów określających modyfikację wag. Przedstawione w pracy wyniki stanowią najbardziej czytelne z uzyskanych. Wizualizacja wielowymiarowa przy użyciu sieci Kohonena pozwala stwierdzić, że informacje zawarte w analizowanych siedmiowymiarowych danych są wystarczające do prawidłowej klasyfikacji typów węgla 31, 34.2 oraz 35, przy czym nawet zobrazowanie 3 typów węgla na jednym rysunku pozwala stwierdzić, że neurony reprezentujące próbki węgla danego typu gromadzą się w skupiskach, które można od siebie odseparować. Z tego wynika, że dane zawierają informacje wystarczające do prawidłowej klasyfikacji węgla. Zauważyć jednak warto, że przedstawienie przy pomocy sieci Kohonena, danych reprezentujących różne typy węgla parami, pozwala uzyskać jeszcze bardziej czytelne wyniki. Najlepsze efekty osiągnięto dla sieci o 40 wierszach oraz 40 kolumnach neuronów, co łącznie dało liczbę 1600 neuronów, zaś czytelność wyników rośnie wraz z postępem uczenia sieci neuronowej (wzrostem parametru ITER). Przeprowadzone doświadczenia w pełni potwierdzają, że zastosowana metoda może być z powodzeniem wykorzystana w badaniach jakościowych związanych z różnego typu materiałami uziarnionymi, w tym również węglem. Badania w tym zakresie są kontynuowane.

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

PubMed

van den Heuvel, E G H M; van Schoor, N M; Vermeer, C; Zwijsen, R M L; den Heijer, M; Comijs, H C

2015-11-01

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. Longitudinal study with six years follow-up. Community based. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Vitamin K

USDA-ARS?s Scientific Manuscript database

Vitamin K, a fat-soluble vitamin, is an enzyme cofactor for post-translation modification of specific glutamate residues that are converted into '-carboxyglutamic acid (Gla) residues by a vitamin K-dependent (VKD) carboxylase. Seven VKD coagulation proteins are synthesized in the liver. The extra-he...

Specific Types of Coal Macerals from Orzesze and Ruda Beds from "Pniówek" Coal Mine (Upper Silesian Coal Basin - Poland) as a Manifestation of Thermal Metamorphism

NASA Astrophysics Data System (ADS)

Adamczyk, Zdzisław; Komorek, Joanna; Lewandowska, Małgorzata

2014-03-01

Subject of the research were coal samples from the seams of Orzesze and Ruda beds from "Pniówek" coal mine. All samples represent methabituminous coal B, which present high vitrinite content (V mmf > 60%). Optical character of vitrinite from all analyzed coal samples is biaxial negative and it is characterized by low differentiation of bireflectance. The experiments have shown that the coal rank of investigated samples is generally decreasing with increasing both depth of coal seams and the distance between sampling point and the Carboniferous roof. It may suggests inversion of coalification. Specific types of macerals, typical for thermally metamorphosed coals have been found for all analysed coal samples. It was found, presence of such components like: fluorescing bituminous substance (FBS) filling of cellular spaces in semifusinite, fusinite, and funginite; pseudomorphs after megaspores exhibiting strong bireflectance, and anisotropic semifusinite. Petrographic components with a structure similar to structure of coke and pyrolytic carbon were observed rarely. Presence of colotelinite grains which are visible darker, impregnated with bituminous substance and exhibiting weak fluorescence may be related with influence of temperature on coal. Carbonates occur as filling of cellular spaces in semifusinite, in examined coal samples and there are the effect of thermal alteration of coal. Przedmiotem badań były próbki węgla z pokładów warstw orzeskich i rudzkich KWK Pniówek. Badane próbki reprezentują węgiel średniouwęglony typu B (metabitumiczny), wysokowitrynitowy. Stwierdzono, że witrynit z badanych próbek ma dwuosiowy ujemny charakter optyczny i wykazuje małe zróżnicowanie w wartościach dwójodbicia. Przeprowadzone badania wykazały, że stopień uwęglenia badanych próbek generalnie maleje wraz ze wzrostem głębokości występowania pokładów węgla oraz ze wzrostem odległości miejsca opróbowania od stropu karbonu co może wskazywać na inwersję uwęglenia. We wszystkich analizowanych próbkach węgla stwierdzono występowanie specyficznych odmian macerałów typowych dla węgli zmetamorfizowanych termicznie. W próbkach stwierdzono obecność takich składników jak: fluoryzująca substancja bitumiczna (FBS) wypełniająca przestrzenie komórkowe w semifuzynicie, fuzynicie i funginicie; pseudomorfozy po makrosporach wykazujące silne dwójodbicie oraz anizotropowy semifuzynit. Rzadziej obserwowano składniki petrograficzne o strukturze wykazującej podobieństwo do struktury koksu i węgiel pirolityczny. Z oddziaływaniem temperatury na badany węgiel można wiązać także obecność w analizowanych próbkach wyraźnie ciemniejszych, przesyconych substancją bitumiczną, wykazujących słabą fluorescencję ziaren kolotelinitu. Przejawem przemian termicznych obserwowanych w badanych próbkach węgla może być także obecność węglanów najczęściej wypełniających przestrzenie komórkowe w semifuzynicie.

Another Way to Divide a Line Segment into "n" Equal Parts

ERIC Educational Resources Information Center

Besteman, Nathan; Ferdinands, John

2005-01-01

Another way to divide a line segment discovered by Nathan Besteman is described along with Euclid's and the GLaD construction. The related projects and problems that teachers of geometry can assign to their students are also presented.

Mars atmospheric circulation - Aspects from Viking Landers

NASA Technical Reports Server (NTRS)

Ryan, J. A.

1985-01-01

Winds measured by the two Viking Landers have been filtered and then compared with predictions from the general circulation model and to Orbiter observations of clouds and surface phenomena that indicate wind direction. This was done to determine the degree to which filtered winds may represent aspects of the general circulation. Excellent agreement was found between wind direction data from Lander 1 and the model predictions and Orbiter observations. For Lander 2, agreement was generally good, but there were periods of disagreement which indicate that the filtering did not remove other extraneous effects. It is concluded that Lander 1 gives a good representation of the general circulation at 22.5 deg N latitude but that Lander 2 is suspect. Most wind data from Lander 1 have yet to be analyzed. It appears that when analyzed these Lander 1 data (covering 3.5 Mars years) can provide information about interannual variations in the general circulation at the Lander latitude.

Modelling of Underground Coal Gasification Process Using CFD Methods / Modelowanie Procesu Podziemnego Zgazowania Węgla Kamiennego Z Zastosowaniem Metod CFD

NASA Astrophysics Data System (ADS)

Wachowicz, Jan; Łączny, Jacek Marian; Iwaszenko, Sebastian; Janoszek, Tomasz; Cempa-Balewicz, Magdalena

2015-09-01

The results of model studies involving numerical simulation of underground coal gasification process are presented. For the purpose of the study, the software of computational fluid dynamics (CFD) was selected for simulation of underground coal gasification. Based on the review of the literature, it was decided that ANSYS-Fluent will be used as software for the performance of model studies. The ANSYS- -Fluent software was used for numerical calculations in order to identify the distribution of changes in the concentration of syngas components as a function of duration of coal gasification process. The nature of the calculations was predictive. A geometric model has been developed based on construction data of the georeactor used during the researches in Experimental Mine "Barbara" and Coal Mine "Wieczorek" and it was prepared by generating a numerical grid. Data concerning the georeactor power supply method and the parameters maintained during the process used to define the numerical model. Some part of data was supplemented based on the literature sources. The main assumption was to base the simulation of the georeactor operation on a mathematical models describing reactive fluid flow. Components of the process gas and the gasification agent move along the gasification channel and simulate physicochemical phenomena associated with the transfer of mass and energy as well as chemical reactions (together with the energy effect). Chemical reactions of the gasification process are based on a kinetic equation which determines the course of a particular type of equation of chemical coal gasification. The interaction of gas with the surrounding coal layer has also been described as a part of the model. The description concerned the transport of thermal energy. The coal seam and the mass rock are treated as a homogeneous body. Modelling studies assumed the coal gasification process is carried out with the participation of separately oxygen and air as a gasification agent, under the specific conditions of the georeactor operations within the time interval of 100 hours and 305 hours. The results of the numerical solution have been compared with the results of experimental results under in-situ conditions. Zaprezentowano wyniki badań modelowych polegających na numerycznej symulacji procesu podziemnego zgazowania węgla. Dla potrzeb realizowanej pracy dokonano wyboru oprogramowania wykorzystywanego do symulacji procesu podziemnego zgazowania węgla. Na podstawie przeglądu literatury zdecydowano, że oprogramowaniem, za pomocą, którego będą realizowane badania modelowe, będzie oprogramowanie informatyczne ANSYS-Fluent. Za jego pomocą przeprowadzano obliczenia numeryczne z zamiarem zidentyfikowania rozkładu zmian stężenia składników gazu procesowego w funkcji czasu trwania procesu zgazowania węgla. Przeprowadzone obliczenia miały charakter predykcji. W oparciu o dane konstrukcyjne georeaktora stosowanego podczas badań na KD Barbara oraz KWK Wieczorek, opracowano model geometryczny oraz wykonano jego dyskretyzację poprzez wygenerowanie odpowiedniej siatki numerycznej w oparciu, o którą wykonywane są obliczenia. Dane dotyczące sposobu zasilania georeaktora oraz parametrów utrzymywanych podczas procesu wykorzystano do definiowania modelu numerycznego. Część danych została uzupełniona w oparciu o źródła literaturowe. Głównym przyjętym założeniem było oparcie symulacji pracy georeaktora o modele opisujące reaktywny przepływ płynu. Składniki gazu procesowego oraz czynnik zgazowujący przemieszczają się wzdłuż kanału zgazowującego symulując zjawiska fizykochemiczne związane z transportem masy i energii oraz zachodzące reakcje chemiczne (wraz z efektem energetycznym). Chemizm procesu zgazowania oparto o równanie kinetyczne, które determinuje przebieg danego typu równania chemicznego zgazowania węgla. W ramach modelu opisano też interakcję gazu z otaczającą warstwą węgla. Opis ten dotyczył transportu energii cieplnej. Warstwę węgla oraz warstwy geologiczne otaczające georeaktor traktuje się jako ciało jednorodne. Badania modelowe zakładały prowadzenie procesu zgazowania calizny węglowej przy udziale, osobno tlenu i powietrza, jako czynnika zgazowującego, w warunkach ustalonych pracy georeaktora w przedziale czasu 100 godzin i 305 godzin. Uzyskane wyniki rozwiązania numerycznego zestawiono z wynikami badań eksperymentalnych w warunkach in-situ.

Au/Si nanorod-based biosensor for food pathogen detection

USDA-ARS?s Scientific Manuscript database

Technical Abstract Among several potentials of nanotechnology applications for food industry, development of nanoscale sensors for food safety and quality measurement are emerging. A novel biosensor for Salmonella detection was developed using Au/Si nanorods. The Si nanorods were fabricated by gla...

Ex-Ante Economic Impact Assessment of Genetically Modified Banana Resistant to Xanthomonas Wilt in the Great Lakes Region of Africa.

PubMed

Ainembabazi, John Herbert; Tripathi, Leena; Rusike, Joseph; Abdoulaye, Tahirou; Manyong, Victor

2015-01-01

Credible empirical evidence is scanty on the social implications of genetically modified (GM) crops in Africa, especially on vegetatively propagated crops. Little is known about the future success of introducing GM technologies into staple crops such as bananas, which are widely produced and consumed in the Great Lakes Region of Africa (GLA). GM banana has a potential to control the destructive banana Xanthomonas wilt disease. To gain a better understanding of future adoption and consumption of GM banana in the GLA countries which are yet to permit the production of GM crops; specifically, to evaluate the potential economic impacts of GM cultivars resistant to banana Xanthomonas wilt disease. The paper uses data collected from farmers, traders, agricultural extension agents and key informants in the GLA. We analyze the perceptions of the respondents about the adoption and consumption of GM crop. Economic surplus model is used to determine future economic benefits and costs of producing GM banana. On the release of GM banana for commercialization, the expected initial adoption rate ranges from 21 to 70%, while the ceiling adoption rate is up to 100%. Investment in the development of GM banana is economically viable. However, aggregate benefits vary substantially across the target countries ranging from US$ 20 million to 953 million, highest in countries where disease incidence and production losses are high, ranging from 51 to 83% of production. The findings support investment in the development of GM banana resistant to Xanthomonas wilt disease. The main beneficiaries of this technology development are farmers and consumers, although the latter benefit more than the former from reduced prices. Designing a participatory breeding program involving farmers and consumers signifies the successful adoption and consumption of GM banana in the target countries.

TITRATION: A Randomized Study to Assess 2 Treatment Algorithms with New Insulin Glargine 300 units/mL.

PubMed

Yale, Jean-François; Berard, Lori; Groleau, Mélanie; Javadi, Pasha; Stewart, John; Harris, Stewart B

2017-10-01

It was uncertain whether an algorithm that involves increasing insulin dosages by 1 unit/day may cause more hypoglycemia with the longer-acting insulin glargine 300 units/mL (GLA-300). The objective of this study was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in people with uncontrolled type 2 diabetes mellitus, mainly in a primary care setting. This was a 12-week, open-label, randomized, multicentre pilot study. Participants were randomly assigned to 1 of 2 algorithms: they either increased their dosage by 1 unit/day (INSIGHT, n=108) or the dose was adjusted by the investigator at least once weekly, but no more often than every 3 days (EDITION, n=104). The target fasting self-monitored blood glucose was in the range of 4.4 to 5.6 mmol/L. The percentages of participants reaching the primary endpoint of fasting self-monitored blood glucose ≤5.6 mmol/L without nocturnal hypoglycemia were 19.4% (INSIGHT) and 18.3% (EDITION). At week 12, 26.9% (INSIGHT) and 28.8% (EDITION) of participants achieved a glycated hemoglobin value of ≤7%. No differences in the incidence of hypoglycemia of any category were noted between algorithms. Participants in both arms of the study were much more satisfied with their new treatment as assessed by the Diabetes Treatment Satisfaction Questionnaire. Most health-care professionals (86%) preferred the INSIGHT over the EDITION algorithm. The frequency of adverse events was similar between algorithms. A patient-driven titration algorithm of 1 unit/day with GLA-300 is effective and comparable to the previously tested EDITION algorithm and is preferred by health-care professionals. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Optimizing Glycemic Control Through Titration of Insulin Glargine 100 U/mL: A Review of Current and Future Approaches with a Focus on Asian Populations.

PubMed

Deerochanawong, Chaicharn; Bajpai, Shailendra; Dwipayana, I Made Pande; Hussein, Zanariah; Mabunay, Maria Aileen; Rosales, Reynaldo; Tsai, Shih-Tzer; Tsang, Man Wo

2017-12-01

Various data have demonstrated inadequate glycemic control amongst Asians with type 2 diabetes mellitus (T2DM), possibly on account of suboptimal titration of basal insulin-an issue which needs to be further examined. Here we review the available global and Asia-specific data on titration of basal insulin, with a focus on the use of insulin glargine 100 U/mL (Gla-100). We also discuss clinical evidence on the efficacy and safety of titrating Gla-100, different approaches to titration, including some of the latest technological advancements, and guidance on the titration of basal insulin from international and local Asian guidelines. The authors also provide their recommendations for the initiation and titration of basal insulin for Asian populations. Discussion of the data included in this review and in relation to the authors' clinical experience with treating T2DM in Asian patients is also included. Briefly, clinical studies demonstrate the achievement of adequate glycemic control in adults with T2DM through titration of Gla-100. However, studies investigating approaches to titration, specifically in Asian populations, are lacking and need to be conducted. Given that the management of insulin therapy is a multidisciplinary team effort involving endocrinologists, primary care physicians, nurse educators, and patients, greater resources and education targeted at these groups are needed regarding the optimal titration of basal insulin. Technological advancements in the form of mobile or web-based applications for automated dose adjustment can aid different stakeholders in optimizing the dose of basal insulin, enabling a larger number of patients in Asia to reach their target glycemic goals with improved outcomes.

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

PubMed

Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P; Viana-Baptista, Miguel; Caldeira-Gomes, António; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C; Oliveira, João Paulo

2015-02-01

Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition. Copyright © 2014 Elsevier Inc. All rights reserved.

The length of the linker between the epidermal growth factor-like domains in factor VIIa is critical for a productive interaction with tissue factor.

PubMed

Persson, Egon; Madsen, Jesper J; Olsen, Ole H

2014-12-01

Formation of the factor VIIa (FVIIa)-tissue factor (TF) complex triggers the blood coagulation cascade. Using a structure-based rationale, we investigated how the length of the linker region between the two epidermal growth factor (EGF)-like domains in FVIIa influences TF binding and the allosteric activity enhancement, as well as the interplay between the γ-carboxyglutamic acid (Gla)-containing and protease domains. Removal of two residues from the native linker was compatible with normal cofactor binding and accompanying stimulation of the enzymatic activity, as was extension by two (Gly-Ser) residues. In sharp contrast, truncation by three or four residues abolished the TF-mediated stabilization of the active conformation of FVIIa and abrogated TF-induced activity enhancement. In addition, FVIIa variants with short linkers associated 80-fold slower with soluble TF (sTF) as compared with wild-type FVIIa, resulting in a corresponding increase in the equilibrium dissociation constant. Molecular modeling suggested that the shortest FVIIa variants would have to be forced into a tense and energetically unfavorable conformation in order to be able to interact productively with TF, explaining our experimental observations. We also found a correlation between linker length and the residual intrinsic enzymatic activity of Ca(2+)-free FVIIa; stepwise truncation resulting in gradually higher activity with des(83-86)-FVIIa reaching the level of Gla-domainless FVIIa. The linker appears to determine the average distance between the negatively charged Gla domain and a structural element in the protease domain, presumably of opposite charge, and proximity has a negative impact on apo-FVIIa activity. © 2014 The Protein Society.

A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.

PubMed

Borrás, Teresa; Smith, Matthew H; Buie, LaKisha K

2015-04-01

Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice. An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry. As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative. Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.

Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients.

PubMed

Boxma, Paul Y; van den Berg, Else; Geleijnse, Johanna M; Laverman, Gozewijn D; Schurgers, Leon J; Vermeer, Cees; Kema, Ido P; Muskiet, Frits A; Navis, Gerjan; Bakker, Stephan J L; de Borst, Martin H

2012-01-01

Vitamin K is essential for activation of γ-carboxyglutamate (Gla)-proteins including the vascular calcification inhibitor matrix Gla-protein (MGP). Insufficient vitamin K intake leads to production of uncarboxylated, mostly inactive proteins and contributes to an increased cardiovascular risk. In kidney transplant recipients, cardiovascular risk is high but vitamin K intake and status have not been defined. We investigated dietary vitamin K intake, vascular vitamin K status and its determinants in kidney transplant recipients. We estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60) with stable renal function (creatinine clearance 61 [42-77] (median [interquartile range]) ml/min), who were 75 [35-188] months after transplantation, using three-day food records and food frequency questionnaires. Vascular vitamin K status was assessed by measuring plasma desphospho-uncarboxylated MGP (dp-ucMGP). Total vitamin K intake was below the recommended level in 50% of patients. Lower vitamin K intake was associated with less consumption of green vegetables (33 vs 40 g/d, p = 0.06) and increased dp-ucMGP levels (621 vs 852 pmol/L, p<0.05). Accordingly, dp-ucMGP levels were elevated (>500 pmol/L) in 80% of patients. Multivariate regression identified creatinine clearance, coumarin use, body mass index, high sensitivity-CRP and sodium excretion as independent determinants of dp-ucMGP levels. In a considerable part of the kidney transplant population, vitamin K intake is too low for maximal carboxylation of vascular MGP. The high dp-ucMGP levels may result in an increased risk for arterial calcification. Whether increasing vitamin K intake may have health benefits for kidney transplant recipients should be addressed by future studies.

Surface-coated fly ash reinforced biodegradable poly(vinyl alcohol) composite films: part 2-analysis and characterization

NASA Astrophysics Data System (ADS)

Nath, D. C. D.; Bandyopadhyay, S.; Campbell, J.; Yu, A.; Blackburn, D.; White, C.

2010-12-01

Composite films of poly(vinyl alcohol) (PVA) reinforced with 5, 10, 15, 20 and 25 wt.% surface-coated fly ash by surfactant, sodium lauryl sulphate (SLS-FA) along with 1 wt.% cross-linking agent, glutaraldehyde (GLA) were prepared by aqueous casting method. The tensile strengths of the composite films were increased proportionally with the addition of SLS-FA. The maximum 75% higher strength of the composite with 20 wt.% was achieved compared to that of neat PVA. The modulus of the composites was also increased proportionally with SLS-FA and the maximum 218% reached in composite with 20 wt.%, but the strain at break was decreased with addition of SLS-FA. Changes in FTIR spectra reflect the chemical and/or physical bonding in the ternary PVA, SLS-FA and GLA component systems. In the study of surface morphology, the connectivity was visualized in SEM images along with interstitial voids. The films with SLS-FA show 53% smoother surface calculated with AFM compared to unmodified FA composite films.

Aeroservoelastic Wind-Tunnel Test of the SUGAR Truss Braced Wing Wind-Tunnel Model

NASA Technical Reports Server (NTRS)

Scott, Robert C.; Allen, Timothy J.; Funk, Christie J.; Castelluccio, Mark A.; Sexton, Bradley W.; Claggett, Scott; Dykman, John; Coulson, David A.; Bartels, Robert E.

2015-01-01

The Subsonic Ultra Green Aircraft Research (SUGAR) Truss-Braced Wing (TBW) aeroservoelastic (ASE) wind-tunnel test was conducted in the NASA Langley Transonic Dynamics Tunnel (TDT) and was completed in April, 2014. The primary goals of the test were to identify the open-loop flutter boundary and then demonstrate flutter suppression. A secondary goal was to demonstrate gust load alleviation (GLA). Open-loop flutter and limit cycle oscillation onset boundaries were identified for a range of Mach numbers and various angles of attack. Two sets of control laws were designed for the model and both sets of control laws were successful in suppressing flutter. Control laws optimized for GLA were not designed; however, the flutter suppression control laws were assessed using the TDT Airstream Oscillation System. This paper describes the experimental apparatus, procedures, and results of the TBW wind-tunnel test. Acquired system ID data used to generate ASE models is also discussed.2 study.

Assessing the impact of different satellite retrieval methods on forecast available potential energy

NASA Technical Reports Server (NTRS)

Whittaker, Linda M.; Horn, Lyle H.

1990-01-01

The effects of the inclusion of satellite temperature retrieval data, and of different satellite retrieval methods, on forecasts made with the NASA Goddard Laboratory for Atmospheres (GLA) fourth-order model were investigated using, as the parameter, the available potential energy (APE) in its isentropic form. Calculation of the APE were used to study the differences in the forecast sets both globally and in the Northern Hemisphere during 72-h forecast period. The analysis data sets used for the forecasts included one containing the NESDIS TIROS-N retrievals, the GLA retrievals using the physical inversion method, and a third, which did not contain satellite data, used as a control; two data sets, with and without satellite data, were used for verification. For all three data sets, the Northern Hemisphere values for the total APE showed an increase throughout the forecast period, mostly due to an increase in the zonal component, in contrast to the verification sets, which showed a steady level of total APE.

Assessment of headlamp glare and potential countermeasures : the effects of headlamp mounting height

DOT National Transportation Integrated Search

2008-01-01

This project examined the effects of headlamp mounting height on the disability and the sensation of discomfort caused by glare. This was performed through a field study and a simulation study. In the field study, subjects evaluated the degree of gla...

A Thermodynamically General Theory for Convective Circulations and Vortices

NASA Astrophysics Data System (ADS)

Renno, N. O.

2007-12-01

Convective circulations and vortices are common features of atmospheres that absorb low-entropy-energy at higher temperatures than they reject high-entropy-energy to space. These circulations range from small to planetary-scale and play an important role in the vertical transport of heat, momentum, and tracer species. Thus, the development of theoretical models for convective phenomena is important to our understanding of many basic features of planetary atmospheres. A thermodynamically general theory for convective circulations and vortices is proposed. The theory includes irreversible processes and quantifies the pressure drop between the environment and any point in a convective updraft. The article's main result is that the proposed theory provides an expression for the pressure drop along streamlines or streamtubes that is a generalization of Bernoulli's equation to convective circulations. We speculate that the proposed theory not only explains the intensity, but also shed light on other basic features of convective circulations and vortices.

Enhancing the hydrogeological landscape (HGL) characterisation of the Greater Launceston area (GLA) through better understanding of dolerite weathering, stream water properties and a revised landscape evolution model

NASA Astrophysics Data System (ADS)

Moore, Leah; Nicholson, Allan; Cook, Wayne; Sweeney, Margaret

2014-05-01

In the Greater Launceston Area (GLA) in northern Tasmania, Australia, there is a widespread urban salinity problem with severe impacts on urban/peri-urban infrastructure in localised areas. Salinity patterns in the landscape (elevated flux to waterways; salt efflorescence at the land surface) could be related to: the underlying rock type, the thickness of regolith materials and hence the volume of the salt store, the landforms present and the amount of water passing over and through the landscape. In northern Tasmania secondary mineralogy on dolerite typically includes formation of Fe/Ca smectite phases (e.g. nontronite, saponite) and Fe-Ti oxides/sesquioxides (e.g. hematite, goethite) with some primary phases (e.g. Ca-plagioclase feldspar, augite) weathering through to a suite dominated by kaolinite clay and Fe-Ti oxides/sesquioxides. Deeply weathered profiles in the GLA have weathered to the kaolintite-clay dominant mineralogy and in places there are gibbsite/beidellite/hematite/goethite bauxites developed. Most existing salinity mapping emphasises salt manifestation over paleo-estuarine sediments of the Paleogene Tamar-Esk River system, so incorporation of deeply weathered Jurassic dolerite materials into the salt budget considerably augments the estimated potential hazard. Rapid stream surveys provide a snapshot of stream electrical conductivity (EC) over the study area at regular intervals allowing a broad evaluation of salt flux patterns in surfaces waters. Higher EC readings were obtained from selected streams draining: deeply weathered dolerite profiles (0.37 1.86 dS/m) and deeply weathered Paleogene paleo-estuarine sediments (0.49 to 1.16 dS/m). Lower values were measured on up-faulted dolerite blocks (<0.10 dS/m); moderately weathered, high relief dolerite (<0.03 dS/m), and in incised streams flowing over a rocky dolerite substrate (<0.03 dS/m). The patterns of stream EC reflect the nature of the regolith materials the streams drain, and match mapped patterns for distribution of deeply weathered Jurassic dolerite and moderately to deeply weathered bedded paleo-estuarine sediments of the Paleogene Tamar-Esk river system, some Quaternary terrace deposits along the Tamar and Esk Rivers; and some Holocene estuarine sediments. Recent geomorphic mapping has enabled development of a more comprehensive and consistent landscape evolution model that builds on existing knowledge. This model describes the influence of a progressively incising Tamar-Esk river system in response to episodic lowering of the local base level, with multiple episodes of valley widening as the river system stabilised after incision. Successive lowering events dissected earlier landforms, but locally remnant surfaces are preserved that represent former fluvial plain and terrace features. These processes were partially controlled by the structural configuration and contrasting resistance of the underlying lithologies, influencing the planform geometries of the rivers, and consequently the potential to preserve paleo-fluvial features. Because the Tamar River is an estuarine system, some of the lowermost preserved surfaces are likely to reflect marine processes (e.g. 5-7m; 10-12m ASL). The geomorphic mapping was conducted independently of the hydrogeological landscape (HGL) characterisation in the GLA, but there is strong correlation between the areas identified as having elevated salinity hazard (HGL) and newly mapped remnant surfaces in this landscape. This work complements HGL research and supports development of an increasingly rigorous evidence-based framework for GLA salinity hazard management.

Circulation control propellers for general aviation, including a BASIC computer program

NASA Technical Reports Server (NTRS)

Taback, I.; Braslow, A. L.; Butterfield, A. J.

1983-01-01

The feasibility of replacing variable pitch propeller mechanisms with circulation control (Coanada effect) propellers on general aviation airplanes was examined. The study used a specially developed computer program written in BASIC which could compare the aerodynamic performance of circulation control propellers with conventional propellers. The comparison of aerodynamic performance for circulation control, fixed pitch and variable pitch propellers is based upon the requirements for a 1600 kg (3600 lb) single engine general aviation aircraft. A circulation control propeller using a supercritical airfoil was shown feasible over a representative range of design conditions. At a design condition for high speed cruise, all three types of propellers showed approximately the same performance. At low speed, the performance of the circulation control propeller exceeded the performance for a fixed pitch propeller, but did not match the performance available from a variable pitch propeller. It appears feasible to consider circulation control propellers for single engine aircraft or multiengine aircraft which have their propellers on a common axis (tractor pusher). The economics of the replacement requires a study for each specific airplane application.

Correlations between the modelled potato crop yield and the general atmospheric circulation

NASA Astrophysics Data System (ADS)

Sepp, Mait; Saue, Triin

2012-07-01

Biology-related indicators do not usually depend on just one meteorological element but on a combination of several weather indicators. One way to establish such integral indicators is to classify the general atmospheric circulation into a small number of circulation types. The aim of present study is to analyse connections between general atmospheric circulation and potato crop yield in Estonia. Meteorologically possible yield (MPY), calculated by the model POMOD, is used to characterise potato crop yield. Data of three meteorological stations and the biological parameters of two potato sorts were applied to the model, and 73 different classifications of atmospheric circulation from catalogue 1.2 of COST 733, domain 05 are used to qualify circulation conditions. Correlation analysis showed that there is at least one circulation type in each of the classifications with at least one statistically significant (99%) correlation with potato crop yield, whether in Kuressaare, Tallinn or Tartu. However, no classifications with circulation types correlating with MPY in all three stations at the same time were revealed. Circulation types inducing a decrease in the potato crop yield are more clearly represented. Clear differences occurred between the observed geographical locations as well as between the seasons: derived from the number of significant circulation types, summer and Kuressaare stand out. Of potato varieties, late 'Anti' is more influenced by circulation. Analysis of MSLP maps of circulation types revealed that the seaside stations (Tallinn, Kuressaare) suffer from negative effects of anti-cyclonic conditions (drought), while Tartu suffers from the cyclonic activity (excessive water).

Relations between winter precipitation and atmospheric circulation simulated by the Geophysical Fluid Dynamics Laboratory general circulation model

USGS Publications Warehouse

McCabe, G.J.; Dettinger, M.D.

1995-01-01

General circulation model (GCM) simulations of atmospheric circulation are more reliable than GCM simulations of temperature and precipitation. In this study, temporal correlations between 700 hPa height anomalies simulated winter precipitation at eight locations in the conterminous United States are compared with corresponding correlations in observations. The objectives are to 1) characterize the relations between atmospheric circulation and winter precipitation simulated by the GFDL, GCM for selected locations in the conterminous USA, ii) determine whether these relations are similar to those found in observations of the actual climate system, and iii) determine if GFDL-simulated precipitation is forced by the same circulation patterns as in the real atmosphere. -from Authors

Interactions among Radiation, Convection, and Large-Scale Dynamics in a General Circulation Model.

NASA Astrophysics Data System (ADS)

Randall, David A.; Harshvardhan; Dazlich, Donald A.; Corsetti, Thomas G.

1989-07-01

We have analyzed the effects of radiatively active clouds on the climate simulated by the UCLA/GLA GCM, with particular attention to the effects of the upper tropospheric stratiform clouds associated with deep cumulus convection, and the interactions of these clouds with convection and the large-scale circulation.Several numerical experiments have been performed to investigate the mechanisms through which the clouds influence the large-scale circulation. In the `NODETLQ' experiment, no liquid water or ice was detrained from cumulus clouds into the environment; all of the condensate was rained out. Upper level supersaturation cloudiness was drastically reduced, the atmosphere dried, and tropical outgoing longwave radiation increased. In the `NOANVIL' experiment, the radiative effects of the optically thich upper-level cloud sheets associated with deep cumulus convection were neglected. The land surface received more solar radiation in regions of convection, leading to enhanced surface fluxes and a dramatic increase in precipitation. In the `NOCRF' experiment, the longwave atmospheric cloud radiative forcing (ACRF) was omitted, paralleling the recent experiment of Slingo and Slingo. The results suggest that the ACRF enhances deep penetrative convection and precipitation, while suppressing shallow convection. They also indicate that the ACRF warms and moistens the tropical troposphere. The results of this experiment are somewhat ambiguous, however; for example, the ACRF suppresses precipitation in some parts of the tropics, and enhances it in others.To isolate the effects of the ACRF in a simpler setting, we have analyzed the climate of an ocean-covered Earth, which we call Seaworld. The key simplicities of Seaworld are the fixed boundary temperature with no land points, the lack of mountains, and the zonal uniformity of the boundary conditions. Results are presented from two Seaworld simulations. The first includes a full suite of physical parameterizations, while the second omits all radiative effects of the clouds. The differences between the two runs are, therefore, entirely due to the direct and indirect and indirect effects of the ACRF. Results show that the ACRF in the cloudy run accurately represents the radiative heating perturbation relative to the cloud-free run. The cloudy run is warmer in the middle troposphere, contains much more precipitable water, and has about 15% more globally averaged precipitation. There is a double tropical rain band in the cloud-free run, and a single, more intense tropical rain band in the cloudy run. The cloud-free run produces relatively weak but frequent cumulus convection, while the cloudy run produces relatively intense but infrequent convection. The mean meridional circulation transport nearly twice as much mass in the cloudy run. The increased tropical rising motion in the cloudy run leads to a deeper boundary layer and also to more moisture in the troposphere above the boundary layer. This accounts for the increased precipitable water content of the atmosphere. The clouds lead to an increase in the intensity of the tropical easterlies, and cause the midlatitude westerly jets to shift equatorward.Taken together, our results show that upper tropospheric clouds associated with moist convection, whose importance has recently been emphasized in observational studies, play a very complex and powerful role in determining the model results. This points to a need to develop more realistic parameterizations of these clouds.

12 CFR 262.3 - Applications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... published. Similarly, the Board will consider comments on an application from the Attorney General or a.... Such notice shall be published in a newspaper of general circulation in— (A) [Reserved] (B) The... published in a newspaper of general circulation in the community or communities in which the head office of...

An Active Flow Circulation Controlled Flap Concept for General Aviation Aircraft Applications

NASA Technical Reports Server (NTRS)

Jones, Gregory S.; Viken, Sally A.; Washburn, Anthony E.; Jenkins, Luther N.; Cagle, C. Mark

2002-01-01

A recent focus on revolutionary aerodynamic concepts has highlighted the technology needs of general aviation and personal aircraft. New and stringent restrictions on these types of aircraft have placed high demands on aerodynamic performance, noise, and environmental issues. Improved high lift performance of these aircraft can lead to slower takeoff and landing speeds that can be related to reduced noise and crash survivability issues. Circulation Control technologies have been around for 65 years, yet have been avoided due to trade offs of mass flow, pitching moment, perceived noise etc. The need to improve the circulation control technology for general aviation and personal air-vehicle applications is the focus of this paper. This report will describe the development of a 2-D General Aviation Circulation Control (GACC) wing concept that utilizes a pulsed pneumatic flap.

Transcriptional, translational, and physiological signatures of undernourished honey bees (Apis mellifera) suggest a role for hormonal factors in hypopharyngeal gland degradation

USDA-ARS?s Scientific Manuscript database

Honey bee colonies function as a superorganism, where facultatively sterile female workers perform various tasks that support the hive. Nurse workers undergo numerous anatomical and physiological changes in preparation for brood rearing, including the growth of hypopharyngeal glands (HGs). These gla...

Adjuvanted multi-epitope vaccines protect HLA-A*1101 transgenic mice against Toxoplasma gondii

USDA-ARS?s Scientific Manuscript database

We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion (GLA-SE)) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included five of our best down selecte...

The association between vitamin K status and knee osteoarthritis features in older adults: the Health, Aging and Body Composition Study

USDA-ARS?s Scientific Manuscript database

Background: Vitamin K-dependent proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence. Objective: To cla...

Euclid, Fibonacci, Sketchpad.

ERIC Educational Resources Information Center

Litchfield, Daniel C.; Goldenheim, David A.

1997-01-01

Describes the solution to a geometric problem by two ninth-grade mathematicians using The Geometer's Sketchpad computer software program. The problem was to divide any line segment into a regular partition of any number of parts, a variation on a problem by Euclid. The solution yielded two constructions, one a GLaD construction and the other using…

Effects of 20 standard amino acids on the growth, total fatty acids production, and γ-linolenic acid yield in Mucor circinelloides.

PubMed

Tang, Xin; Zhang, Huaiyuan; Chen, Haiqin; Chen, Yong Q; Chen, Wei; Song, Yuanda

2014-12-01

Twenty standard amino acids were examined as single nitrogen source on the growth, total fatty acids production, and yield of γ-linolenic acid (GLA) in Mucor circinelloides. Of the amino acids, tyrosine gave the highest biomass and lipid accumulation and thus resulted in a high GLA yield with respective values of 17.8 g/L, 23 % (w/w, dry cell weight, DCW), and 0.81 g/L, which were 36, 25, and 72 % higher than when the fungus was grown with ammonium tartrate. To find out the potential mechanism underlying the increased lipid accumulation of M. circinelloides when grown on tyrosine, the activity of lipogenic enzymes of the fungus during lipid accumulation phase was measured. The enzyme activities of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and ATP-citrate lyase were up-regulated, while NADP-isocitrate dehydrogenase was down-regulated by tyrosine during the lipid accumulation phase of the fungus which suggested that these enzymes may be involved in the increased lipid biosynthesis by tyrosine in this fungus.

An Inactivated Rabies Virus–Based Ebola Vaccine, FILORAB1, Adjuvanted With Glucopyranosyl Lipid A in Stable Emulsion Confers Complete Protection in Nonhuman Primate Challenge Models

PubMed Central

Johnson, Reed F.; Kurup, Drishya; Hagen, Katie R.; Fisher, Christine; Keshwara, Rohan; Papaneri, Amy; Perry, Donna L.; Cooper, Kurt; Jahrling, Peter B.; Wang, Jonathan T.; ter Meulen, Jan; Wirblich, Christoph; Schnell, Matthias J.

2016-01-01

The 2013–2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus–based EBOV vaccine, in rhesus and cynomolgus monkeys. Our results demonstrate that the use of the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid A in stable emulsion (GLA-SE) as an adjuvant increased the efficacy of FILORAB1 to 100% protection against lethal EBOV challenge, with no to mild clinical signs of disease. Furthermore, all vaccinated subjects developed protective anti–rabies virus antibody titers. Taken together, these results support further development of FILORAB1/GLA-SE as an effective preexposure EBOV vaccine. PMID:27456709

Comparative study of lipids in mature seeds of six Cordia species (family Boraginaceae) collected in different regions of Brazil.

PubMed

Carvalho, Patricía de O; Arrebola, Melissa B; Sawaya, Alexandra C H F; Cunha, Ildenize B S; Bastos, Deborah H M; Eberlin, Marcos N

2006-08-01

The oil content, FA, and lipid class composition of the mature seeds of six Cordia species were analyzed. Mature seeds of each species were collected in their natural habitat from 2002 to 2004. The total lipid content varied from 1.9% to 13.2%, there being significant differences between the results found in different years for each species and between the species analyzed. The contents of FFA varied from 2.0% to 7.9% of total lipids. Neutral lipids (NL) were the largest class, making up between 89.6% and 96.4% of the total lipids; the phospholipids (PL) were the second largest class (3.0% to 8.9% of the total lipids), and the glycolipids (GL) were the smallest class (0.6 to 3.4%). The presence of GLA was determined in each class of lipids; it is predominant in the NL. Levels of GLA ranged from 1.2% to 6.8% of total seed FA. This is, to our knowledge the first study of lipid composition in seeds of species of Cordia from Brazil.

Application of Silver Ion High-Performance Liquid Chromatography for Quantitative Analysis of Selected n-3 and n-6 PUFA in Oil Supplements.

PubMed

Czajkowska-Mysłek, Anna; Siekierko, Urszula; Gajewska, Magdalena

2016-04-01

The aim of this study was to develop a simple method for simultaneous determination of selected cis/cis PUFA-LNA (18:2), ALA (18:3), GLA (18:3), EPA (20:5), and DHA (22:6) by silver ion high-performance liquid chromatography coupled to a diode array detector (Ag-HPLC-DAD). The separation was performed on three Luna SCX Silver Loaded columns connected in series maintained at 10 °C with isocratic elution by 1% acetonitrile in n-hexane. The applied chromatographic system allowed a baseline separation of standard mixture of n-3 and n-6 fatty acid methyl esters containing LNA, DHA, and EPA and partial separation of ALA and GLA positional isomers. The method was validated by means of linearity, precision, stability, and recovery. Limits of detection (LOD) for considered PUFA standard solutions ranged from 0.27 to 0.43 mg L(-1). The developed method was used to evaluate of n-3 and n-6 fatty acids contents in plant and fish softgel oil capsules, results were compared with reference GC-FID based method.

Evaluation and Sensitivity Analysis of an Ocean Model Response to Hurricane Ivan (PREPRINT)

DTIC Science & Technology

2009-05-18

analysis of upper-limb meridional overturning circulation interior ocean pathways in the tropical/subtropical Atlantic . In: Interhemispheric Water...diminishing returns are encountered when either resolution is increased. 3 1. Introduction Coupled ocean-atmosphere general circulation models have become...northwest Caribbean Sea 4 and GOM. Evaluation is difficult because ocean general circulation models incorporate a large suite of numerical algorithms

Decreased undercarboxylated osteocalcin in children with type 2 diabetes mellitus.

PubMed

Takaya, Junji; Tanabe, Yuko; Kuroyanagi, Yuichi; Kaneko, Kazunari

2016-08-01

Osteocalcin (OC) is a bone-specific protein secreted by osteoblasts and often used as a bone formation biomarker. OC undergoes post-translational carboxylation to yield carboxylated osteocalcin (Gla-OC) and undercarboxylated osteocalcin (uc-OC) molecules. The aim of this study was to explore the association between bone and glucose metabolism by evaluating OC, ionized cations, and markers of glucose metabolism in children with obesity and type 2 diabetes mellitus (DM2). The subjects were nine children with DM2 [six males, three females; age 15.7±4.1 years; duration of disease 3.2±1.2 years], 18 children with simple obesity [12 males, six females; age 12.6±4.1 years], and 12 controls [eight males, four females; age 12.3±3.2 years]. Serum Gla-OC and uc-OC levels were determined using an enzyme-linked immunosorbent assay (ELISA). Patients with DM2 (0.65±0.46 ng/mL), but not with obesity (1.11±0.55 ng/mL), had lower uc-OC levels than controls (1.25±0.49 ng/mL). Serum uc-OC was negatively correlated with mean serum glucose levels (r=-0.447, p=0.013) and hemoglobin A1c (HbA1c) (r=-0.455, p=0.012) in all subjects. Serum Gla-OC was correlated with serum alkaline phosphatase (r=0.601, p<0.001) and inorganic phosphorus (r=0.686, p<0.001), yet negatively correlated with age (r=-0.383, p=0.030). Mean serum ionized magnesium was lower in DM2 subjects than in controls. Mean serum ionized calcium was higher in obese subjects than in controls. In all subjects, mean serum ionized magnesium was negatively correlated with mean serum glucose levels. Osteoblast-derived protein OC, especially uc-OC, may have a role in the pathophysiology of diabetes by being associated with blood glucose homeostasis.

Ex-Ante Economic Impact Assessment of Genetically Modified Banana Resistant to Xanthomonas Wilt in the Great Lakes Region of Africa

PubMed Central

Ainembabazi, John Herbert; Tripathi, Leena; Rusike, Joseph; Abdoulaye, Tahirou; Manyong, Victor

2015-01-01

Background Credible empirical evidence is scanty on the social implications of genetically modified (GM) crops in Africa, especially on vegetatively propagated crops. Little is known about the future success of introducing GM technologies into staple crops such as bananas, which are widely produced and consumed in the Great Lakes Region of Africa (GLA). GM banana has a potential to control the destructive banana Xanthomonas wilt disease. Objective To gain a better understanding of future adoption and consumption of GM banana in the GLA countries which are yet to permit the production of GM crops; specifically, to evaluate the potential economic impacts of GM cultivars resistant to banana Xanthomonas wilt disease. Data Sources The paper uses data collected from farmers, traders, agricultural extension agents and key informants in the GLA. Analysis We analyze the perceptions of the respondents about the adoption and consumption of GM crop. Economic surplus model is used to determine future economic benefits and costs of producing GM banana. Results On the release of GM banana for commercialization, the expected initial adoption rate ranges from 21 to 70%, while the ceiling adoption rate is up to 100%. Investment in the development of GM banana is economically viable. However, aggregate benefits vary substantially across the target countries ranging from US$ 20 million to 953 million, highest in countries where disease incidence and production losses are high, ranging from 51 to 83% of production. Conclusion The findings support investment in the development of GM banana resistant to Xanthomonas wilt disease. The main beneficiaries of this technology development are farmers and consumers, although the latter benefit more than the former from reduced prices. Designing a participatory breeding program involving farmers and consumers signifies the successful adoption and consumption of GM banana in the target countries. PMID:26414379

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment.

PubMed

Eguchi, Takanori; Sogawa, Chiharu; Okusha, Yuka; Uchibe, Kenta; Iinuma, Ryosuke; Ono, Kisho; Nakano, Keisuke; Murakami, Jun; Itoh, Manabu; Arai, Kazuya; Fujiwara, Toshifumi; Namba, Yuri; Murata, Yoshiki; Ohyama, Kazumi; Shimomura, Manami; Okamura, Hirohiko; Takigawa, Masaharu; Nakatsura, Tetsuya; Kozaki, Ken-Ichi; Okamoto, Kuniaki; Calderwood, Stuart K

2018-01-01

Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression.

Awareness of Fabry disease in cardiology: A gap to be filled.

PubMed

Brito, Dulce; Cardim, Nuno; Lopes, Luís Rocha; Belo, Adriana; Mimoso, Jorge; Gonçalves, Lino; Madeira, Hugo

2018-06-01

In adults, unexplained left ventricular hypertrophy is usually due to sarcomeric hypertrophic cardiomyopathy (HCM). Fabry disease (FD) is rare but may mimic sarcomeric HCM, and has an adverse prognosis in the absence of specific treatment. We aimed to assess cardiologists' awareness of FD based on data from the Portuguese Registry of Hypertrophic Cardiomyopathy. A total of 811 index patients, aged 55 ± 16 years, 486 (59.9%) male, were included. Three groups were characterized: A - 128 patients, 74 (57.8%) male, with pathogenic or likely pathogenic mutation(s) in sarcomeric genes; B - 234 patients, 146 (62.4%) male, with negative genetic testing; and C - 449 patients, 266 (59.2%) male, no genetic testing performed. The groups were compared in terms of whether FD was excluded in the registry. Potential red flags for FD were also analyzed and compared between groups. Patients in group A were younger and more frequently had familial HCM (A - 53.9% vs. B - 20.1% vs. C - 18.3%; p <0.001). FD was recorded as excluded in 217 (26.8%), similar in all groups; GLA gene testing was performed in only 50/217 patients (A - 48.6%, B - 25.7%, p = 0.019; C - 13.4%, p = 0.036 for B vs. C), mostly in women (p <0.001) in groups B and C. Alpha-galactosidase A (α-Gal A) activity was assessed in 39/217 (18%) patients, with no difference between groups, but more often in men (p = 0.005). Among patients with potential red flags for FD, only 46.7% underwent specific tests (GLA gene testing and/or α-Gal A activity). When GLA genotyping was performed no mutations were identified. There is a need to improve cardiologists' alertness for the identification of FD among the Portuguese HCM population. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases

PubMed Central

Viegas, Carla S. B.; Costa, Rúben M.; Santos, Lúcia; Videira, Paula A.; Silva, Zélia; Araújo, Nuna; Macedo, Anjos L.; Matos, António P.; Vermeer, Cees; Simes, Dina C.

2017-01-01

Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and γ-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein γ-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNFα, IL-1β and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application. PMID:28542410

Adjuvant composition and delivery route shape immune response quality and protective efficacy of a recombinant vaccine for Entamoeba histolytica.

PubMed

Abhyankar, Mayuresh M; Orr, Mark T; Lin, Susan; Suraju, Mohammed O; Simpson, Adrian; Blust, Molly; Pham, Tiep; Guderian, Jeffrey A; Tomai, Mark A; Elvecrog, James; Pedersen, Karl; Petri, William A; Fox, Christopher B

2018-01-01

Amebiasis caused by Entamoeba histolytic a is the third leading cause of parasitic mortality globally, with some 100,000 deaths annually, primarily among young children. Protective immunity to amebiasis is associated with fecal IgA and IFN-γ in humans; however, no vaccine exists. We have previously identified recombinant LecA as a potential protective vaccine antigen. Here we describe the development of a stable, manufacturable PEGylated liposomal adjuvant formulation containing two synthetic Toll-like receptor (TLR) ligands: GLA (TLR4) and 3M-052 (TLR7/8). The liposomes stimulated production of monocyte/macrophage chemoattractants MCP-1 and Mip-1β, and Th1-associated cytokines IL-12p70 and IFN-γ from human whole blood dependent on TLR ligand composition and dose. The liposomes also demonstrated acceptable physicochemical compatibility with the recombinant LecA antigen. Whereas mice immunized with LecA and GLA-liposomes demonstrated enhanced antigen-specific fecal IgA titers, mice immunized with LecA and 3M-052-liposomes showed a stronger Th1 immune profile. Liposomes containing GLA and 3M-052 together elicited both LecA-specific fecal IgA and Th1 immune responses. Furthermore, the quality of the immune response could be modulated with modifications to the liposomal formulation based on PEG length. Compared to subcutaneous administration, the optimized liposome adjuvant composition with LecA antigen administered intranasally resulted in significantly enhanced fecal IgA, serum IgG2a, as well as systemic IFN-γ and IL-17A levels in mice. The optimized intranasal regimen provided greater than 80% protection from disease as measured by parasite antigen in the colon. This work demonstrates the physicochemical and immunological characterization of an optimized mucosal adjuvant system containing a combination of TLR ligands with complementary activities and illustrates the importance of adjuvant composition and route of delivery to enhance a multifaceted and protective immune response to amebiasis.

Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment

PubMed Central

Okusha, Yuka; Uchibe, Kenta; Iinuma, Ryosuke; Ono, Kisho; Nakano, Keisuke; Murakami, Jun; Itoh, Manabu; Arai, Kazuya; Fujiwara, Toshifumi; Namba, Yuri; Murata, Yoshiki; Ohyama, Kazumi; Shimomura, Manami; Okamura, Hirohiko; Takigawa, Masaharu; Nakatsura, Tetsuya; Kozaki, Ken-ichi; Okamoto, Kuniaki; Calderwood, Stuart K.

2018-01-01

Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression. PMID:29415026

Impact of variations of gravitational acceleration on the general circulation of the planetary atmosphere

NASA Astrophysics Data System (ADS)

Kilic, Cevahir; Raible, Christoph C.; Stocker, Thomas F.; Kirk, Edilbert

2017-01-01

Fundamental to the redistribution of energy in a planetary atmosphere is the general circulation and its meridional structure. We use a general circulation model of the atmosphere in an aquaplanet configuration with prescribed sea surface temperature and investigate the influence of the gravitational acceleration g on the structure of the circulation. For g =g0 = 9.81 ms-2 , three meridional cells exist in each hemisphere. Up to about g /g0 = 1.4 all cells increase in strength. Further increasing this ratio results in a weakening of the thermally indirect cell, such that a two- and finally a one-cell structure of the meridional circulation develops in each hemisphere. This transition is explained by the primary driver of the thermally direct Hadley cell: the diabatic heating at the equator which is proportional to g. The analysis of the energetics of the atmospheric circulation based on the Lorenz energy cycle supports this finding. For Earth-like gravitational accelerations transient eddies are primarily responsible for the meridional heat flux. For large gravitational accelerations, the direct zonal mean conversion of energy dominates the meridional heat flux.

Balanced and Unbalanced Aspects of Tropical Cyclone Intensification

DTIC Science & Technology

2009-10-06

axisymmetric balance theory. The secondary ( overturning ) circulation and balanced tendency for the primary circulation are obtained by solving a...balance theory. The secondary ( overturning ) circulation and balanced tendency for the primary circulation are obtained by solving a general form of the... meridional circulation . This equation is often referred to as the Sawyer–Eliassen (SE) equation (Willoughby, 1979; Shapiro and Willoughby, 1982). For

Optimal Diphthongs: An OT Analysis of the Acquisition of Spanish Diphthongs

ERIC Educational Resources Information Center

Krause, Alice

2013-01-01

This dissertation investigates the acquisition of Spanish diphthongs by adult native speakers of English. The following research questions will be addressed: 1) How do adult native speakers of English pronounce sequences of two vowels in their L2 Spanish at different levels of acquisition? 2) Can OT learnability models, specifically the GLA,…

Sol-Gel Processing Science Using a Sol-Gel Optics Research Facility (SGORF)

DTIC Science & Technology

1989-09-10

Malaysia , Hong-Kong) where labor rates are perhaps one-tenth those of the U.S.. Figure 1 presents the trends of imports and exports of all optical... ACerS Annual Meeting, Washington, DC, May 1972. 2. W. A. Plummer, "Differential Dilatometry--A Powerful Tool," Corning Gla 33 Works, Corning, NY 14830

The novel cyst nematode effector protein 19C07 interacts with the Arabidopsis auxin influx transporter LAX3 to control feeding site development

USDA-ARS?s Scientific Manuscript database

Plant-parasitic cyst nematodes penetrate plant roots and transform cells near the vasculature into specialized feeding sites, called syncytia. Syncytia form by incorporating neighboring cells into a single fused cell by cell wall dissolution. This process is initiated via injection of esophageal gla...

Movers, Shakers, & Everyone in Between: Faculty Personas Surrounding Active Learning in the Undergraduate STEM Classroom

ERIC Educational Resources Information Center

Guy, Batsheva R.

2017-01-01

This qualitative study explores the attitudes that STEM (Science, Technology, Engineering, and Mathematics) faculty have about active learning (AL), the barriers that STEM faculty face when implementing AL, and what would encourage STEM faculty to use AL. Data was gathered using a modified Group-Level Assessment (GLA), a participatory method meant…

A Constraint-Based Approach to Acquisition of Word-Final Consonant Clusters in Turkish Children

ERIC Educational Resources Information Center

Gokgoz-Kurt, Burcu

2017-01-01

The current study provides a constraint-based analysis of L1 word-final consonant cluster acquisition in Turkish child language, based on the data originally presented by Topbas and Kopkalli-Yavuz (2008). The present analysis was done using [?]+obstruent consonant cluster acquisition. A comparison of Gradual Learning Algorithm (GLA) under…

The influence of the tropics upon the prediction of the Southern Hemisphere circulation within the GLAS GCM. [Goddard Laboratory for Atmospheric Sciences General Circulation Model

NASA Technical Reports Server (NTRS)

Baker, W. E.; Paegle, J.

1983-01-01

An examination is undertaken of the sensitivity of short term Southern Hemisphere circulation prediction to tropical wind data and tropical latent heat release. The data assimilation experiments employ the Goddard Laboratory for Atmospheric Sciences' fourth-order general circulation model. Two of the experiments are identical, but for the fact that one uses tropical wind data while the other does not. A third experiment contains the identical initial conditions of forecasts with tropical winds, while suppressing tropical latent heat release.

Feasibility study: Atmospheric general circulation experiment, volume 2

NASA Technical Reports Server (NTRS)

Homsey, R. J. (Editor)

1981-01-01

The feasibility analysis of the atmospheric general circulation experiment (AGCE) are documented. The analysis performed in each technical area, the rationale and substantiation for the design approaches selected for the hardware, and the design details for the baseline AGCE are presented.

Vertical Helicity Flux as an Index of General Atmospheric Circulation

NASA Astrophysics Data System (ADS)

Kurgansky, M. V.; Maksimenkov, L. O.; Khapaev, A. A.; Chkhetiani, O. G.

2018-04-01

As an index of the general atmospheric circulation over the hemisphere, it is proposed to calculate the hemisphere-area-averaged (poleward of the latitude 20°) product of the Coriolis parameter by the wind velocity squared at the upper boundary of the planetary boundary layer. In practical calculations, data on the wind velocity at an isobaric level of 850 hPa were used. Control calculations for the 900 hPa level gave similar results. It is shown that the index introduced adequately characterizes the seasonal and interannual variability of the general atmospheric circulation over both hemispheres.

Calibrating the ECCO ocean general circulation model using Green's functions

NASA Technical Reports Server (NTRS)

Menemenlis, D.; Fu, L. L.; Lee, T.; Fukumori, I.

2002-01-01

Green's functions provide a simple, yet effective, method to test and calibrate General-Circulation-Model(GCM) parameterizations, to study and quantify model and data errors, to correct model biases and trends, and to blend estimates from different solutions and data products.

General Anesthesia Inhibits the Activity of the “Glymphatic System”

PubMed Central

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; Martinez de Lizarrondo, Sara; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the “glymphatic system” hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent. PMID:29344300

General Anesthesia Inhibits the Activity of the "Glymphatic System".

PubMed

Gakuba, Clement; Gaberel, Thomas; Goursaud, Suzanne; Bourges, Jennifer; Di Palma, Camille; Quenault, Aurélien; de Lizarrondo, Sara Martinez; Vivien, Denis; Gauberti, Maxime

2018-01-01

INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS: In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.

Atmospheric Diabatic Heating in Different Weather States and the General Circulation

NASA Technical Reports Server (NTRS)

Rossow, William B.; Zhang, Yuanchong; Tselioudis, George

2016-01-01

Analysis of multiple global satellite products identifies distinctive weather states of the atmosphere from the mesoscale pattern of cloud properties and quantifies the associated diabatic heating/cooling by radiative flux divergence, precipitation, and surface sensible heat flux. The results show that the forcing for the atmospheric general circulation is a very dynamic process, varying strongly at weather space-time scales, comprising relatively infrequent, strong heating events by ''stormy'' weather and more nearly continuous, weak cooling by ''fair'' weather. Such behavior undercuts the value of analyses of time-averaged energy exchanges in observations or numerical models. It is proposed that an analysis of the joint time-related variations of the global weather states and the general circulation on weather space-time scales might be used to establish useful ''feedback like'' relationships between cloud processes and the large-scale circulation.

Thermospheric dynamics during November 21-22, 1981 - Dynamics Explorer measurements and thermospheric general circulation model predictions

NASA Technical Reports Server (NTRS)

Roble, R. G.; Killeen, T. L.; Spencer, N. W.; Heelis, R. A.; Reiff, P. H.

1988-01-01

Time-dependent aurora and magnetospheric convection parameterizations have been derived from solar wind and aurora particle data for November 21-22, 1981, and are used to drive the auroral and magnetospheric convection models that are embedded in the National Center for Atmospheric Research thermospheric general circulation model (TGCM). Neutral wind speeds and transition boundaries between the midlatitude solar-driven circulation and the high-latitude magnetospheric convection-driven circulation are examined on an orbit-by-orbit basis. The results show that TGCM-calculated winds and reversal boundary locations are in generally good agreement with Dynamics Explorer 2 measurements for the orbits studied. This suggests that, at least for this particular period of relatively moderate geomagnetic activity, the TGCM parameterizations on the eveningside of the auroral oval and polar cap are adequate.

Clarifying the Dynamics of the General Circulation: Phillips's 1956 Experiment.

NASA Astrophysics Data System (ADS)

Lewis, John M.

1998-01-01

In the mid-1950s, amid heated debate over the physical mechanisms that controlled the known features of the atmosphere's general circulation, Norman Phillips simulated hemispheric motion on the high-speed computer at the Institute for Advanced Study. A simple energetically consistent model was integrated for a simulated time of approximately 1 month. Analysis of the model results clarified the respective roles of the synoptic-scale eddies (cyclones-anticyclones) and mean meridional circulation in the maintenance of the upper-level westerlies and the surface wind regimes. Furthermore, the modeled cyclones clearly linked surface frontogenesis with the upper-level Charney-Eady wave. In addition to discussing the model results in light of the controversy and ferment that surrounded general circulation theory in the 1940s-1950s, an effort is made to follow Phillips's scientific path to the experiment.

A Nonlinear Multigrid Solver for an Atmospheric General Circulation Model Based on Semi-Implicit Semi-Lagrangian Advection of Potential Vorticity

NASA Technical Reports Server (NTRS)

McCormick, S.; Ruge, John W.

1998-01-01

This work represents a part of a project to develop an atmospheric general circulation model based on the semi-Lagrangian advection of potential vorticity (PC) with divergence as the companion prognostic variable.

Assimilation of TOPEX/POSEIDON Altimeter Data into a Global Ocean Circulation Model: Are the Results Any Good?

NASA Technical Reports Server (NTRS)

Fukumori, I.; Fu, L. L.; Chao, Y.

1998-01-01

The feasibility of assimilating satellite altimetry data into a global ocean general ocean general circulation model is studied. Three years of TOPEX/POSEIDON data is analyzed using a global, three-dimensional, nonlinear primitive equation model.

Integration of a highly ordered gold nanowires array with glucose oxidase for ultra-sensitive glucose detection.

PubMed

Cui, Jiewu; Adeloju, Samuel B; Wu, Yucheng

2014-01-27

A highly sensitive amperometric nanobiosensor has been developed by integration of glucose oxidase (GO(x)) with a gold nanowires array (AuNWA) by cross-linking with a mixture of glutaraldehyde (GLA) and bovine serum albumin (BSA). An initial investigation of the morphology of the synthesized AuNWA by field emission scanning electron microscopy (FESEM) and field emission transmission electron microscopy (FETEM) revealed that the nanowires array was highly ordered with rough surface, and the electrochemical features of the AuNWA with/without modification were also investigated. The integrated AuNWA-BSA-GLA-GO(x) nanobiosensor with Nafion membrane gave a very high sensitivity of 298.2 μA cm(-2) mM(-1) for amperometric detection of glucose, while also achieving a low detection limit of 0.1 μM, and a wide linear range of 5-6000 μM. Furthermore, the nanobiosensor exhibited excellent anti-interference ability towards uric acid (UA) and ascorbic acid (AA) with the aid of Nafion membrane, and the results obtained for the analysis of human blood serum indicated that the device is capable of glucose detection in real samples. Copyright © 2013 Elsevier B.V. All rights reserved.

An Inactivated Rabies Virus-Based Ebola Vaccine, FILORAB1, Adjuvanted With Glucopyranosyl Lipid A in Stable Emulsion Confers Complete Protection in Nonhuman Primate Challenge Models.

PubMed

Johnson, Reed F; Kurup, Drishya; Hagen, Katie R; Fisher, Christine; Keshwara, Rohan; Papaneri, Amy; Perry, Donna L; Cooper, Kurt; Jahrling, Peter B; Wang, Jonathan T; Ter Meulen, Jan; Wirblich, Christoph; Schnell, Matthias J

2016-10-15

The 2013-2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus-based EBOV vaccine, in rhesus and cynomolgus monkeys. Our results demonstrate that the use of the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid A in stable emulsion (GLA-SE) as an adjuvant increased the efficacy of FILORAB1 to 100% protection against lethal EBOV challenge, with no to mild clinical signs of disease. Furthermore, all vaccinated subjects developed protective anti-rabies virus antibody titers. Taken together, these results support further development of FILORAB1/GLA-SE as an effective preexposure EBOV vaccine. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

G.L. Amidon, H. Lennernas, V.P. Shah, and J.R. Crison. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995--backstory of BCS.

PubMed

Shah, Vinod P; Amidon, Gordon L

2014-09-01

The Biopharmaceutics Classification System (BCS) has become widely accepted today in the academic, industrial, and regulatory world. While the initial application of the BCS was to regulatory science bioequivalence (BE) issues and related implications, it has come to be utilized widely by the pharmaceutical industry in drug discovery and development as well. This brief manuscript will relate the story of the BCS development. While much of the ground work for the BCS goes back to the pharmacokinetic and drug absorption research by Gordon Amidon (GLA) in the 1970s and 1980s, the realization of the need for a classification or categorization of drug and drug products for setting dissolution standards became apparent to GLA during his 1990-1991 sabbatical year at the FDA. Initiated at the invitation of the then CEDR director, Dr. Carl Peck, to become a visiting scientist at the FDA, the goal was to promote regulatory research at the FDA, in my case, in biopharmaceutics, and to develop a science-based system to simplify regulatory requirements.

Matrix Gla Protein Polymorphisms are Associated with Coronary Artery Calcification in Men

PubMed Central

Crosier, Michael D.; Booth, Sarah L.; Peter, Inga; Dawson-Hughes, Bess; Price, Paul A.; O’Donnell, Christopher J.; Hoffmann, Udo; Williamson, Matthew K.; Ordovas, Jose M.

2009-01-01

Summary Matrix Gla protein (MGP) is a key regulator of vascular calcification. Genetic variation at the MGP locus could modulate the development of coronary artery calcification (CAC). Our aim was to examine the cross-sectional association between MGP single nucleotide polymorphisms (SNPs) [rs1800802 (T-138C), rs1800801 (G-7A), and rs4236 (Ala102Thr)] and CAC. CAC was measured by multidetector computed tomography (MDCT), in older men and women of European descent, (n = 386; 60 to 80 y of age). Serum MGP was measured by radioimmunoassay. Linear, Tobit and Ordinal regression analyses all revealed that in men, homozygous carriers of the minor allele of rs1800802 , rs1800801 , or rs4236 (minor allele frequency: 21, 38, and 40%, respectively) were associated with a decreased quantity of CAC, relative to major allele carriers. This association was not found in women. Although genetic variation in MGP was associated with serum MGP concentrations, there were no associations between serum MGP and CAC. The results of this study suggest a role for MGP genetic variants in coronary atherosclerosis among men that is not reflected in serum MGP concentrations. PMID:19352064

Recombinant Human Factor IX Produced from Transgenic Porcine Milk

PubMed Central

Lee, Meng-Hwan; Lin, Yin-Shen; Tu, Ching-Fu; Yen, Chon-Ho

2014-01-01

Production of biopharmaceuticals from transgenic animal milk is a cost-effective method for highly complex proteins that cannot be efficiently produced using conventional systems such as microorganisms or animal cells. Yields of recombinant human factor IX (rhFIX) produced from transgenic porcine milk under the control of the bovine α-lactalbumin promoter reached 0.25 mg/mL. The rhFIX protein was purified from transgenic porcine milk using a three-column purification scheme after a precipitation step to remove casein. The purified protein had high specific activity and a low ratio of the active form (FIXa). The purified rhFIX had 11.9 γ-carboxyglutamic acid (Gla) residues/mol protein, which approached full occupancy of the 12 potential sites in the Gla domain. The rhFIX was shown to have a higher isoelectric point and lower sialic acid content than plasma-derived FIX (pdFIX). The rhFIX had the same N-glycosylation sites and phosphorylation sites as pdFIX, but had a higher specific activity. These results suggest that rhFIX produced from porcine milk is physiologically active and they support the use of transgenic animals as bioreactors for industrial scale production in milk. PMID:24955355

Simulation of seasonal cloud forcing anomalies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randall, D.A.

1990-08-01

One useful way to classify clouds is according to the processes that generate them. There are three main cloud-formation agencies: deep convection; surface evaporation; large-scale lifting in the absence of conditional instability. Although traditionally clouds have been viewed as influencing the atmospheric general circulation primarily through the release of latent heat, the atmospheric science literature contains abundant evidence that, in reality, clouds influence the general circulation through four more or less equally important effects: interactions with the solar and terrestrial radiation fields; condensation and evaporation; precipitation; small-scale circulations within the atmosphere. The most advanced of the current generation of GCMsmore » include parameterizations of all four effects. Until recently there has been lingering skepticism, in the general circulation modeling community, that the radiative effects of clouds significantly influence the atmospheric general circulation. GCMs have provided the proof that the radiative effects of clouds are important for the general circulation of the atmosphere. An important concept in analysis of the effects of clouds on climate is the cloud radiative forcing (CRF), which is defined as the difference between the radiative flux which actually occurs in the presence of clouds, and that which would occur if the clouds were removed but the atmospheric state were otherwise unchanged. We also use the term CRF to denote warming or cooling tendencies due to cloud-radiation interactions. Cloud feedback is the change in CRF that accompanies a climate change. The present study concentrates on the planetary CRF and its response to external forcing, i.e. seasonal change.« less

A Regression Study of Demand, Cost and Pricing Public Library Circulation Services.

ERIC Educational Resources Information Center

Stratton, Peter J.

This paper examines three aspects of the public library's circulation service: (1) a demand function for the service is estimated; (2) a long-run unit circulation cost curve is developed; and (3) using the economist's notion of "efficiency," a general model for the pricing of the circulation service is presented. The estimated demand…

40 CFR 93.156 - Public participation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... placing a notice by prominent advertisement in a daily newspaper of general circulation in the area....158 for a Federal action by placing a notice by prominent advertisement in a daily newspaper of... placing a notice by prominent advertisement in a daily newspaper of general circulation in the area...

A Wind Tunnel Model to Explore Unsteady Circulation Control for General Aviation Applications

NASA Technical Reports Server (NTRS)

Cagle, Christopher M.; Jones, Gregory S.

2002-01-01

Circulation Control airfoils have been demonstrated to provide substantial improvements in lift over conventional airfoils. The General Aviation Circular Control model is an attempt to address some of the concerns of this technique. The primary focus is to substantially reduce the amount of air mass flow by implementing unsteady flow. This paper describes a wind tunnel model that implements unsteady circulation control by pulsing internal pneumatic valves and details some preliminary results from the first test entry.

Documentation of the GLAS fourth order general circulation model. Volume 1: Model documentation

NASA Technical Reports Server (NTRS)

Kalnay, E.; Balgovind, R.; Chao, W.; Edelmann, J.; Pfaendtner, J.; Takacs, L.; Takano, K.

1983-01-01

The volume 1, of a 3 volume technical memoranda which contains a documentation of the GLAS Fourth Order General Circulation Model is presented. Volume 1 contains the documentation, description of the stratospheric/tropospheric extension, user's guide, climatological boundary data, and some climate simulation studies.

General circulation of the South Atlantic between 5 deg N and 35 deg S

NASA Technical Reports Server (NTRS)

Ollitrault, Michel; Mercier, H.; Blanc, F.; Letraon, L. Y.

1991-01-01

The TOPEX/POSEIDON altimeter will provide the temporal mean seal level. So, secondly, we propose to compute the difference between these two surfaces (mean sea level minus general circulation dynamic topography). The result will be an estimate of the marine geoid, which is time invariant for the 5-year period under consideration. If this geoid is precise enough, it will permit a description of seasonal variability of the large-scale surface circulation. If there happens to be enough float data, it may be possible to infer the first vertical modes of this variability. Thus the main goal of our investigation is to determine the 3-D general circulation of the South Atlantic and the large-scale seasonal fluctuations. This last objective, however, may be restricted to the western part of the South Atlantic because float deployments have been scheduled only in the Brasil basin.

Numerical simulation of the circulation of the atmosphere of Titan

NASA Technical Reports Server (NTRS)

Hourdin, F.; Levan, P.; Talagrand, O.; Courtin, Regis; Gautier, Daniel; Mckay, Christopher P.

1992-01-01

A three dimensional General Circulation Model (GCM) of Titan's atmosphere is described. Initial results obtained with an economical two dimensional (2D) axisymmetric version of the model presented a strong superrotation in the upper stratosphere. Because of this result, a more general numerical study of superrotation was started with a somewhat different version of the GCM. It appears that for a slowly rotating planet which strongly absorbs solar radiation, circulation is dominated by global equator to pole Hadley circulation and strong superrotation. The theoretical study of this superrotation is discussed. It is also shown that 2D simulations systemically lead to instabilities which make 2D models poorly adapted to numerical simulation of Titan's (or Venus) atmosphere.

Cloud-radiative effects on implied oceanic energy transport as simulated by atmospheric general circulation models

NASA Technical Reports Server (NTRS)

Gleckler, P. J.; Randall, D. A.; Boer, G.; Colman, R.; Dix, M.; Galin, V.; Helfand, M.; Kiehl, J.; Kitoh, A.; Lau, W.

1995-01-01

This paper summarizes the ocean surface net energy flux simulated by fifteen atmospheric general circulation models constrained by realistically-varying sea surface temperatures and sea ice as part of the Atmospheric Model Intercomparison Project. In general, the simulated energy fluxes are within the very large observational uncertainties. However, the annual mean oceanic meridional heat transport that would be required to balance the simulated surface fluxes is shown to be critically sensitive to the radiative effects of clouds, to the extent that even the sign of the Southern Hemisphere ocean heat transport can be affected by the errors in simulated cloud-radiation interactions. It is suggested that improved treatment of cloud radiative effects should help in the development of coupled atmosphere-ocean general circulation models.

Cyclonic circulation of Saturn's atmosphere due to tilted convection

NASA Astrophysics Data System (ADS)

Afanasyev, Y. D.; Zhang, Y.

2018-03-01

Saturn displays cyclonic vortices at its poles and the general atmospheric circulation at other latitudes is dominated by embedded zonal jets that display cyclonic circulation. The abundance of small-scale convective storms suggests that convection plays a role in producing and maintaining Saturn's atmospheric circulation. However, the dynamical influence of small-scale convection on Saturn's general circulation is not well understood. Here we present laboratory analogue experiments and propose that Saturn's cyclonic circulation can be explained by tilted convection in which buoyancy forces do not align with the planet's rotation axis. In our experiments—conducted with a cylindrical water tank that is heated at the bottom, cooled at the top and spun on a rotating table—warm rising plumes and cold sinking water generate small anticyclonic and cyclonic vortices that are qualitatively similar to Saturn's convective storms. Numerical simulations complement the experiments and show that this small-scale convection leads to large-scale cyclonic flow at the surface and anticyclonic circulation at the base of the fluid layer, with a polar vortex forming from the merging of smaller cyclonic storms that are driven polewards.

Observations and Modeling of the Transient General Circulation of the North Pacific Basin

NASA Technical Reports Server (NTRS)

McWilliams, James C.

2000-01-01

Because of recent progress in satellite altimetry and numerical modeling and the accumulation and archiving of long records of hydrographic and meteorological variables, it is becoming feasible to describe and understand the transient general circulation of the ocean (i.e., variations with spatial scales larger than a few hundred kilometers and time scales of seasonal and longer-beyond the mesoscale). We have carried out various studies in investigation of the transient general circulation of the Pacific Ocean from a coordinated analysis of satellite altimeter data, historical hydrographic gauge data, scatterometer wind observations, reanalyzed operational wind fields, and a variety of ocean circulation models. Broadly stated, our goal was to achieve a phenomenological catalogue of different possible types of large-scale, low-frequency variability, as a context for understanding the observational record. The approach is to identify the simplest possible model from which particular observed phenomena can be isolated and understood dynamically and then to determine how well these dynamical processes are represented in more complex Oceanic General Circulation Models (OGCMs). Research results have been obtained on Rossby wave propagation and transformation, oceanic intrinsic low-frequency variability, effects of surface gravity waves, pacific data analyses, OGCM formulation and developments, and OGCM simulations of forced variability.

The importance of non-quasigeostrophic forcing during the development of a blocking anticyclone

NASA Technical Reports Server (NTRS)

Tsou, Chih-Hua; Smith, Phillip J.

1990-01-01

This study examines the impact of non-quasigeostrophic (NQG) processes during the development of a blocking anticyclone (January 21, 1979 over the southern tip of Greenland) and a precursor, upstream intense cyclone (January 18, 1979). Energy quantities and height tendencies determined from quasigeostrophic estimates are compared with the same quantities obtained from more general formulations. GLA FGGE Level III-b analysis on a 4 deg lat by 5 deg long grid was used to obtain energetics results. It is concluded that NQG processes strengthened the intensity of the block and a precursor explosive cyclone and that a portion of this increase resulted from enhanced baroclinic conversion of eddy potential to eddy kinetic energy and reduced barotropic energy conversion from eddy to zonal flow. It is suggested that NQG vorticity advection, instead of moderating wave developments, enhanced the block development, and it is also suggested that QG forcing might not have been adequate to produce the observed block development.

Identifying the Strengths, Needs, and Barriers to Student Success for First Generation, Low-Income, First Year College Students

ERIC Educational Resources Information Center

Hayes, Linda A.

2013-01-01

This participatory action research needs assessment was to empower the students in a large urban research university to explore and to identify the strengths of the program, to identify the needs, and to identify the barriers to student success during their first year of college. Using qualitative methods of Group Level Interviews (GLA) and…

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

PubMed

Oster, Gerry; Sullivan, Sean D; Dalal, Mehul R; Kazemi, Mahmood R; Rojeski, Maria; Wysham, Carol H; Sung, Jennifer; Johnstone, Bryan; Cali, Anna M G; Wei, L J; Traylor, Louise; Anhalt, Henry; Hull, Michelle; Van Vleet, John; Meneghini, Luigi F

2016-11-01

This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites. Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. www.clinicaltrials.gov identifier is NCT02451137.

How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

PubMed Central

Rodriguez-Teja, Mercedes; Breit, Claudia; Clarke, Mitchell; Talar, Kamil; Wang, Kai; Mohammad, Mohammad A.; Pickwell, Sage; Etchandy, Guillermina; Stasiuk, Graeme J.; Sturge, Justin

2016-01-01

Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed. PMID:27684203

Total chemical synthesis of human matrix Gla protein

PubMed Central

Hackeng, Tilman M.; Rosing, Jan; Spronk, Henri M.H.; Vermeer, Cees

2001-01-01

Human matrix Gla protein (MGP) is a vitamin K–dependent extracellular matrix protein that binds Ca2+ ions and that is involved in the prevention of vascular calcification. MGP is a 10.6-kD protein (84 amino acids) containing five γ-carboxyglutamic acid (Gla) residues and one disulfide bond. Studies of the mechanism by which MGP prevents calcification of the arterial media are hampered by the low solubility of the protein (<10 μg/mL). Because of solubility problems, processing of a recombinantly expressed MGP-fusion protein chimera to obtain MGP was unsuccessful. Here we describe the total chemical synthesis of MGP by tBoc solid-phase peptide synthesis (SPPS) and native chemical ligation. Peptide Tyr1-Ala53 was synthesized on a derivatized resin yielding a C-terminal thioester group. Peptide Cys54-Lys84 was synthesized on Lys-PAM resin yielding a C-terminal carboxylic acid. Subsequent native chemical ligation of the two peptides resulted in the formation of a native peptide bond between Ala53 and Cys54. Folding of the 1–84-polypeptide chain in 3 M guanidine (pH 8) resulted in a decrease of molecular mass from 10,605 to 10,603 (ESI-MS), representing the loss of two protons because of the formation of the Cys54-Cys60 internal disulfide bond. Like native MGP, synthetic MGP had the same low solubility when brought into aqueous buffer solutions with physiological salt concentrations, confirming its native like structure. However, the solubility of MGP markedly increased in borate buffer at pH 7.4 in the absence of sodium chloride. Ca2+-binding to MGP was confirmed by analytical HPLC, on which the retention time of MGP was reduced in the presence of CaCl2. Circular dichroism studies revealed a sharp increase in α-helicity at 0.2 mM CaCl2 that may explain the Ca2+-dependent shift in high-pressure liquid chromatography (HPLC)-retention time of MGP. In conclusion, facile and efficient chemical synthesis in combination with native chemical ligation yielded MGP preparations that can aid in unraveling the mechanism by which MGP prevents vascular calcification. PMID:11274477

40 CFR 147.3101 - Public notice of permit actions.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., the Director shall also publish notice in a daily or weekly newspaper of general circulation in the... requirements of § 124.10 of this chapter, the Director shall provide to the affected Tribal government all... permit, shall publish such notice in at least two newspapers of general circulation in the area of the...

On the design of an interactive biosphere for the GLAS general circulation model

NASA Technical Reports Server (NTRS)

Mintz, Y.; Sellers, P. J.; Willmott, C. J.

1983-01-01

Improving the realism and accuracy of the GLAS general circulation model (by adding an interactive biosphere that will simulate the transfers of latent and sensible heat from land surface to atmosphere as functions of the atmospheric conditions and the morphology and physiology of the vegetation) is proposed.

Stratospheric wind errors, initial states and forecast skill in the GLAS general circulation model

NASA Technical Reports Server (NTRS)

Tenenbaum, J.

1983-01-01

Relations between stratospheric wind errors, initial states and 500 mb skill are investigated using the GLAS general circulation model initialized with FGGE data. Erroneous stratospheric winds are seen in all current general circulation models, appearing also as weak shear above the subtropical jet and as cold polar stratospheres. In this study it is shown that the more anticyclonic large-scale flows are correlated with large forecast stratospheric winds. In addition, it is found that for North America the resulting errors are correlated with initial state jet stream accelerations while for East Asia the forecast winds are correlated with initial state jet strength. Using 500 mb skill scores over Europe at day 5 to measure forecast performance, it is found that both poor forecast skill and excessive stratospheric winds are correlated with more anticyclonic large-scale flows over North America. It is hypothesized that the resulting erroneous kinetic energy contributes to the poor forecast skill, and that the problem is caused by a failure in the modeling of the stratospheric energy cycle in current general circulation models independent of vertical resolution.

Global Observations and Understanding of the General Circulation of the Oceans

NASA Technical Reports Server (NTRS)

1984-01-01

The workshop was organized to: (1) assess the ability to obtain ocean data on a global scale that could profoundly change our understanding of the circulation; (2) identify the primary and secondary elements needed to conduct a World Ocean Circulation Experiment (WOCE); (3) if the ability is achievable, to determine what the U.S. role in such an experiment should be; and (4) outline the steps necessary to assure that an appropriate program is conducted. The consensus of the workshop was that a World Ocean Circulation Experiment appears feasible, worthwhile, and timely. Participants did agree that such a program should have the overall goal of understanding the general circulation of the global ocean well enough to be able to predict ocean response and feedback to long-term changes in the atmosphere. The overall goal, specific objectives, and recommendations for next steps in planning such an experiment are included.

Quasi-periodic oscillations in a symmetric general circulation model

NASA Technical Reports Server (NTRS)

Goswami, B. N.; Shukla, J.

1984-01-01

Observational evidence has been presented for the existence of quasi-periodic fluctuations of the tropical circulation with periods around two weeks and around 40 days. It is expected that an understanding of the mechanisms of these quasi-periodic oscillations in the tropical atmosphere will improve the predictability of the short range climate fluctuations in the tropics. The present study evolved as an outgrowth of an investigation conducted by Goswami et al. (1984). In this investigation remarkable oscillations of the Hadlay circulation for an ocean covered earth were observed. In the current study evidence is presented regarding the episodic behavior of the tropical circulation in general, and the propagation characteristics of these oscillations in the lower atmosphere. Attention is given to the results of six different experiments.

On the Freshwater Sensitivity of the Arctic-Atlantic Thermohaline Circulation

NASA Astrophysics Data System (ADS)

Lambert, E.; Eldevik, T.; Haugan, P.

2016-02-01

The North Atlantic thermohaline circulation (THC) carries heat and salt toward the Arctic. This circulation is generally believed to be inhibited by northern freshwater input as indicated by the `box-model' of Stommel (1961). The inferred freshwater-sensitivity of the THC, however, varies considerably between studies, both quantitatively and qualitatively. The northernmost branch of the Atlantic THC, which forms a double estuarine circulation in the Arctic Mediterranean, is one example where both strengthening and weakening of the circulation may occur due to increased freshwater input. We have accordingly built on Stommel's original concept to accomodate a THC similar to that in the Arctic Mediterranean. This model consists of three idealized basins, or boxes, connected by two coupled branches of circulation - the double estuary. The net transport of these two branches represents the extension of the Gulf Stream toward the Arctic. Its sensitivity to a change in freshwater forcing depends largely on the distribution of freshwater over the two northern basins. Varying this distribution opens a spectrum of qualitative behaviours ranging from Stommel's original freshwater-inhibited overturning circulation to a freshwater-facilitated estuarine circulation. Between these limiting cases, a Hopf and a cusp bifurcation divide the spectrum into three qualitative regions. In the first region, the circulation behaves similarly to Stommel's circulation, and sufficient freshwater input can induce an abrupt transition into a reversed flow; in the second, a similar transition can be found, although it does not reverse the circulation; in the third, no transition can occur and the circulation is generally facilitated by the northern freshwater input. Overall, the northern THC appears more stable than what would be inferred based on Stommel's model; it requires a larger amount and more localized freshwater input to `collapse' it, and a double estuary circulation is less prone to flow reversal.

Combination of TOPEX/POSEIDON Data with a Hydrographic Inversion for Determination of the Oceanic General Circulation and its Relation to Geoid Accuracy

NASA Technical Reports Server (NTRS)

Ganachaud, Alexandre; Wunsch, Carl; Kim, Myung-Chan; Tapley, Byron

1997-01-01

A global estimate of the absolute oceanic general circulation from a geostrophic inversion of in situ hydrographic data is tested against and then combined with an estimate obtained from TOPEX/POSEIDON altimetric data and a geoid model computed using the JGM-3 gravity-field solution. Within the quantitative uncertainties of both the hydrographic inversion and the geoid estimate, the two estimates derived by very different methods are consistent. When the in situ inversion is combined with the altimetry/geoid scheme using a recursive inverse procedure, a new solution, fully consistent with both hydrography and altimetry, is found. There is, however, little reduction in the uncertainties of the calculated ocean circulation and its mass and heat fluxes because the best available geoid estimate remains noisy relative to the purely oceanographic inferences. The conclusion drawn from this is that the comparatively large errors present in the existing geoid models now limit the ability of satellite altimeter data to improve directly the general ocean circulation models derived from in situ measurements. Because improvements in the geoid could be realized through a dedicated spaceborne gravity recovery mission, the impact of hypothetical much better, future geoid estimates on the circulation uncertainty is also quantified, showing significant hypothetical reductions in the uncertainties of oceanic transport calculations. Full ocean general circulation models could better exploit both existing oceanographic data and future gravity-mission data, but their present use is severely limited by the inability to quantify their error budgets.

Documentation of the GLAS fourth order general circulation model. Volume 2: Scalar code

NASA Technical Reports Server (NTRS)

Kalnay, E.; Balgovind, R.; Chao, W.; Edelmann, D.; Pfaendtner, J.; Takacs, L.; Takano, K.

1983-01-01

Volume 2, of a 3 volume technical memoranda contains a detailed documentation of the GLAS fourth order general circulation model. Volume 2 contains the CYBER 205 scalar and vector codes of the model, list of variables, and cross references. A variable name dictionary for the scalar code, and code listings are outlined.

Development and validation of a colorimetric assay for simultaneous quantification of neutral and uronic sugars.

PubMed

Rondel, Caroline; Marcato-Romain, Claire-Emmanuelle; Girbal-Neuhauser, Elisabeth

2013-05-15

A colorimetric assay based on the conventional anthrone reaction was investigated for specific quantification of uronic acids (UA) in the presence of neutral sugars and/or proteins. Scanning of glucose (Glu) and glucuronic acid (GlA) was performed after the reaction with anthrone and a double absorbance reading was made, at 560 nm and at 620 nm, in order to quantify the UA and neutral sugars separately. The assay was implemented on binary or ternary solutions containing Glu, GlA and bovine serum albumin (BSA) in order to validate its specificity towards sugars and check possible interference with other biochemical components such as proteins. Statistical analysis indicated that this assay provided correct quantification of uronic sugars from 50 to 400 mg/l and of neutral sugars from 20 to 80 mg/l, in the presence of proteins with concentrations reaching 600 mg/l. The proposed protocol can be of great interest for simultaneous determination of uronic and neutral sugars in complex biological samples. In particular, it can be used to correctly quantify the Extracellular Polymeric Substances (EPS) isolated from the biological matrix of many bacterial aggregates, even in the presence of EPS extractant such as EDTA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glassy-State Stabilization of a Dominant Negative Inhibitor Anthrax Vaccine Containing Aluminum Hydroxide and Glycopyranoside Lipid A Adjuvants

PubMed Central

Hassett, Kimberly J.; Vance, David J.; Jain, Nishant K.; Sahni, Neha; Rabia, Lilia A.; Cousins, Megan C.; Joshi, Sangeeta; Volkin, David B.; Middaugh, Russell; Mantis, Nicholas J.; Carpenter, John F.; Randolph, Theodore W.

2014-01-01

During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, Dominant Negative Inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40 °C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40 °C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40 °C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40 °C was observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose. PMID:25581103

Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis.

PubMed

Cavaco, Sofia; Viegas, Carla S B; Rafael, Marta S; Ramos, Acácio; Magalhães, Joana; Blanco, Francisco J; Vermeer, Cees; Simes, Dina C

2016-03-01

Osteoarthritis (OA) is a whole-joint disease characterized by articular cartilage loss, tissue inflammation, abnormal bone formation and extracellular matrix (ECM) mineralization. Disease-modifying treatments are not yet available and a better understanding of osteoarthritis pathophysiology should lead to the discovery of more effective treatments. Gla-rich protein (GRP) has been proposed to act as a mineralization inhibitor and was recently shown to be associated with OA in vivo. Here, we further investigated the association of GRP with OA mineralization-inflammation processes. Using a synoviocyte and chondrocyte OA cell system, we showed that GRP expression was up-regulated following cell differentiation throughout ECM calcification, and that inflammatory stimulation with IL-1β results in an increased expression of COX2 and MMP13 and up-regulation of GRP. Importantly, while treatment of articular cells with γ-carboxylated GRP inhibited ECM calcification, treatment with either GRP or GRP-coated basic calcium phosphate (BCP) crystals resulted in the down-regulation of inflammatory cytokines and mediators of inflammation, independently of its γ-carboxylation status. Our results strengthen the calcification inhibitory function of GRP and strongly suggest GRP as a novel anti-inflammatory agent, with potential beneficial effects on the main processes responsible for osteoarthritis progression. In conclusion, GRP is a strong candidate target to develop new therapeutic approaches.

Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.

PubMed

Borgonio-Cuadra, Verónica Marusa; González-Huerta, Norma Celia; Rojas-Toledo, Emma Xochitl; Morales-Hernández, Eugenio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Tovilla-Zárate, Carlos Alfonso; González-Castro, Thelma Beatriz; Hernández-Díaz, Yazmín; López-Narváez, María Lilia; Miranda-Duarte, Antonio

2018-05-18

Primary osteoarthritis (OA) is a complex entity in which several loci related to different molecular pathways or classes of molecules are associated with its development as demonstrated through genetic association studies. Genes involved in bone formation and mineralization, such as osteopontin (OPN) and Matrix Gla protein (MGP), could also be related with OA. The aim of this study was to evaluate the association between the genetic variants of OPN and MGP with primary knee osteoarthritis in a Mexican population. A case-control study was conducted in 296 patients with primary knee osteoarthritis and in 354 control subjects. Study groups were assessed radiologically. The rs11730582 of OPN and rs1800802, rs1800801, and rs4236 of MGP were determined by TaqMan allele discrimination assays. The haplotypes of the polymorphisms of MGP were constructed. The association was tested through univariate and multivariate non-conditional logistic regression analyses. The polymorphisms of MGP complied with Hardy-Weinberg (HW) equilibrium. The polymorphisms of OPN and MGP were not significantly associated with primary knee osteoarthritis in the codominant, dominant, and recessive models (p > 0.05). Our study suggests that there are no associations between OPN and MGP polymorphisms with primary knee osteoarthritis in Mexican population.

Automated Circulation Systems as a Source of Secondary Information.

ERIC Educational Resources Information Center

Chapin, Giny Ziegler

This report looks at the use of public library online circulation systems for the generation of in-house secondary information--such as statistical reports and mailing lists--and also considers problems in maintaining confidentiality of patron records when using online circulation systems. Based on a survey of the literature, general information…

Simulation of seasonal anomalies of atmospheric circulation using coupled atmosphere-ocean model

NASA Astrophysics Data System (ADS)

Tolstykh, M. A.; Diansky, N. A.; Gusev, A. V.; Kiktev, D. B.

2014-03-01

A coupled atmosphere-ocean model intended for the simulation of coupled circulation at time scales up to a season is developed. The semi-Lagrangian atmospheric general circulation model of the Hydrometeorological Centre of Russia, SLAV, is coupled with the sigma model of ocean general circulation developed at the Institute of Numerical Mathematics, Russian Academy of Sciences (INM RAS), INMOM. Using this coupled model, numerical experiments on ensemble modeling of the atmosphere and ocean circulation for up to 4 months are carried out using real initial data for all seasons of an annual cycle in 1989-2010. Results of these experiments are compared to the results of the SLAV model with the simple evolution of the sea surface temperature. A comparative analysis of seasonally averaged anomalies of atmospheric circulation shows prospects in applying the coupled model for forecasts. It is shown with the example of the El Niño phenomenon of 1997-1998 that the coupled model forecasts the seasonally averaged anomalies for the period of the nonstationary El Niño phase significantly better.

Radiation and Dissipation of Internal Waves Generated by Geostrophic Motions Impinging on Small-Scale Topography

DTIC Science & Technology

2009-02-01

the largest zonal current in the world, which links the Atlantic , Indian and Pacific Oceans. The associated Meridional Overturning Circulation (MOC...formed in polar regions (Wunsch and Ferrari, 2004). Mixing is especially important in the Southern Ocean where the Meridional Overturning Circulation ...general circulation of the ocean and an important driver of the lower cell of the Meridional Overturning Circulation . Wunsch (1998) estimated that the

36 CFR 910.17 - Pedestrian circulation system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... GENERAL GUIDELINES AND UNIFORM STANDARDS FOR URBAN PLANNING AND DESIGN OF DEVELOPMENT WITHIN THE PENNSYLVANIA AVENUE DEVELOPMENT AREA Urban Planning and Design Concerns § 910.17 Pedestrian circulation system...

36 CFR 910.17 - Pedestrian circulation system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... GENERAL GUIDELINES AND UNIFORM STANDARDS FOR URBAN PLANNING AND DESIGN OF DEVELOPMENT WITHIN THE PENNSYLVANIA AVENUE DEVELOPMENT AREA Urban Planning and Design Concerns § 910.17 Pedestrian circulation system...

The influence of surface waves on water circulation in a mid-Atlantic continental shelf region

NASA Technical Reports Server (NTRS)

Whitlock, C. H.; Talay, T. A.

1974-01-01

The importance of wave-induced currents in different weather conditions and water depths (18.3 m and 36.6 m) is assessed in a mid-Atlantic continental-shelf region. A review of general circulation conditions is conducted. Factors which perturb the general circulation are examined using analytic techniques and limited experimental data. Actual wind and wave statistics for the region are examined. Relative magnitudes of the various currents are compared on a frequency of annual occurrence basis. Results indicated that wave-induced currents are often the same order of magnitude as other currents in the region and become more important at higher wind and wave conditions. Wind-wave and ocean-swell characteristics are among those parameters which must be monitored for the analytical computation of continental-shelf circulation.

Uncertainties in Carbon Dioxide Radiative Forcing in Atmospheric General Circulation Models

NASA Technical Reports Server (NTRS)

Cess, R. D.; Zhang, M.-H.; Potter, G. L.; Gates, W. L.; Taylor, K. E.; Barker, H. W.; Colman, R. A.; Fraser, J. R.; McAvaney, B. J.; Dazlich, D. A.;

Performance Analysis and Optimization on the UCLA Parallel Atmospheric General Circulation Model Code

NASA Technical Reports Server (NTRS)

Lou, John; Ferraro, Robert; Farrara, John; Mechoso, Carlos

1996-01-01

An analysis is presented of several factors influencing the performance of a parallel implementation of the UCLA atmospheric general circulation model (AGCM) on massively parallel computer systems. Several modificaitons to the original parallel AGCM code aimed at improving its numerical efficiency, interprocessor communication cost, load-balance and issues affecting single-node code performance are discussed.

Simulation of the early Martian climate using a general circulation model, DRAMATIC MGCM: Impacts of thermal inertia

NASA Astrophysics Data System (ADS)

Kamada, A.; Kuroda, T.; Kasaba, Y.; Terada, N.; Akiba, T.

2017-09-01

Our Mars General Circulation Model was used to reproduce the early Martian climate which was thought to be warm and wet. Our simulation with high thermal inertia assuming wet soils and ancient ocean/lakes succeeded in producing the surface temperature above 273K throughout a year in low-mid latitudes of northern hemisphere.

Efficient quantum circuits for dense circulant and circulant like operators

PubMed Central

Zhou, S. S.

2017-01-01

Circulant matrices are an important family of operators, which have a wide range of applications in science and engineering-related fields. They are, in general, non-sparse and non-unitary. In this paper, we present efficient quantum circuits to implement circulant operators using fewer resources and with lower complexity than existing methods. Moreover, our quantum circuits can be readily extended to the implementation of Toeplitz, Hankel and block circulant matrices. Efficient quantum algorithms to implement the inverses and products of circulant operators are also provided, and an example application in solving the equation of motion for cyclic systems is discussed. PMID:28572988

The intra- and extracellular proteome of Aspergillus niger growing on defined medium with xylose or maltose as carbon substrate.

PubMed

Lu, Xin; Sun, Jibin; Nimtz, Manfred; Wissing, Josef; Zeng, An-Ping; Rinas, Ursula

2010-04-20

The filamentous fungus Aspergillus niger is well-known as a producer of primary metabolites and extracellular proteins. For example, glucoamylase is the most efficiently secreted protein of Aspergillus niger, thus the homologous glucoamylase (glaA) promoter as well as the glaA signal sequence are widely used for heterologous protein production. Xylose is known to strongly repress glaA expression while maltose is a potent inducer of glaA promoter controlled genes. For a more profound understanding of A. niger physiology, a comprehensive analysis of the intra- and extracellular proteome of Aspergillus niger AB1.13 growing on defined medium with xylose or maltose as carbon substrate was carried out using 2-D gel electrophoresis/Maldi-ToF and nano-HPLC MS/MS. The intracellular proteome of A. niger growing either on xylose or maltose in well-aerated controlled bioreactor cultures revealed striking similarities. In both cultures the most abundant intracellular protein was the TCA cycle enzyme malate-dehydrogenase. Moreover, the glycolytic enzymes fructose-bis-phosphate aldolase and glyceraldehyde-3-phosphate-dehydrogenase and the flavohemoglobin FhbA were identified as major proteins in both cultures. On the other hand, enzymes involved in the removal of reactive oxygen species, such as superoxide dismutase and peroxiredoxin, were present at elevated levels in the culture growing on maltose but only in minor amounts in the xylose culture. The composition of the extracellular proteome differed considerably depending on the carbon substrate. In the secretome of the xylose-grown culture, a variety of plant cell wall degrading enzymes were identified, mostly under the control of the xylanolytic transcriptional activator XlnR, with xylanase B and ferulic acid esterase as the most abundant ones. The secretome of the maltose-grown culture did not contain xylanolytic enzymes, instead high levels of catalases were found and glucoamylase (multiple spots) was identified as the most abundant extracellular protein. Surprisingly, the intracellular proteome of A. niger growing on xylose in bioreactor cultures differed more from a culture growing in shake flasks using the same medium than from the bioreactor culture growing on maltose. For example, in shake flask cultures with xylose as carbon source the most abundant intracellular proteins were not the glycolytic and the TCA cycle enzymes and the flavohemoglobin, but CipC, a protein of yet unknown function, superoxide dismutase and an NADPH dependent aldehyde reductase. Moreover, vacuolar proteases accumulated to higher and ER-resident chaperones and foldases to lower levels in shake flask compared to the bioreactor cultures. The utilization of xylose or maltose was strongly affecting the composition of the secretome but of minor influence on the composition of the intracellular proteome. On the other hand, differences in culture conditions (pH control versus no pH control, aeration versus no aeration and stirring versus shaking) have a profound effect on the intracellular proteome. For example, lower levels of ER-resident chaperones and foldases and higher levels of vacuolar proteases render shake flask conditions less favorable for protein production compared to controlled bioreactor cultures.

The intra- and extracellular proteome of Aspergillus niger growing on defined medium with xylose or maltose as carbon substrate

PubMed Central

2010-01-01

Background The filamentous fungus Aspergillus niger is well-known as a producer of primary metabolites and extracellular proteins. For example, glucoamylase is the most efficiently secreted protein of Aspergillus niger, thus the homologous glucoamylase (glaA) promoter as well as the glaA signal sequence are widely used for heterologous protein production. Xylose is known to strongly repress glaA expression while maltose is a potent inducer of glaA promoter controlled genes. For a more profound understanding of A. niger physiology, a comprehensive analysis of the intra- and extracellular proteome of Aspergillus niger AB1.13 growing on defined medium with xylose or maltose as carbon substrate was carried out using 2-D gel electrophoresis/Maldi-ToF and nano-HPLC MS/MS. Results The intracellular proteome of A. niger growing either on xylose or maltose in well-aerated controlled bioreactor cultures revealed striking similarities. In both cultures the most abundant intracellular protein was the TCA cycle enzyme malate-dehydrogenase. Moreover, the glycolytic enzymes fructose-bis-phosphate aldolase and glyceraldehyde-3-phosphate-dehydrogenase and the flavohemoglobin FhbA were identified as major proteins in both cultures. On the other hand, enzymes involved in the removal of reactive oxygen species, such as superoxide dismutase and peroxiredoxin, were present at elevated levels in the culture growing on maltose but only in minor amounts in the xylose culture. The composition of the extracellular proteome differed considerably depending on the carbon substrate. In the secretome of the xylose-grown culture, a variety of plant cell wall degrading enzymes were identified, mostly under the control of the xylanolytic transcriptional activator XlnR, with xylanase B and ferulic acid esterase as the most abundant ones. The secretome of the maltose-grown culture did not contain xylanolytic enzymes, instead high levels of catalases were found and glucoamylase (multiple spots) was identified as the most abundant extracellular protein. Surprisingly, the intracellular proteome of A. niger growing on xylose in bioreactor cultures differed more from a culture growing in shake flasks using the same medium than from the bioreactor culture growing on maltose. For example, in shake flask cultures with xylose as carbon source the most abundant intracellular proteins were not the glycolytic and the TCA cycle enzymes and the flavohemoglobin, but CipC, a protein of yet unknown function, superoxide dismutase and an NADPH dependent aldehyde reductase. Moreover, vacuolar proteases accumulated to higher and ER-resident chaperones and foldases to lower levels in shake flask compared to the bioreactor cultures. Conclusions The utilization of xylose or maltose was strongly affecting the composition of the secretome but of minor influence on the composition of the intracellular proteome. On the other hand, differences in culture conditions (pH control versus no pH control, aeration versus no aeration and stirring versus shaking) have a profound effect on the intracellular proteome. For example, lower levels of ER-resident chaperones and foldases and higher levels of vacuolar proteases render shake flask conditions less favorable for protein production compared to controlled bioreactor cultures. PMID:20406453

Methods of testing parameterizations: Vertical ocean mixing

NASA Technical Reports Server (NTRS)

Tziperman, Eli

1992-01-01

The ocean's velocity field is characterized by an exceptional variety of scales. While the small-scale oceanic turbulence responsible for the vertical mixing in the ocean is of scales a few centimeters and smaller, the oceanic general circulation is characterized by horizontal scales of thousands of kilometers. In oceanic general circulation models that are typically run today, the vertical structure of the ocean is represented by a few tens of discrete grid points. Such models cannot explicitly model the small-scale mixing processes, and must, therefore, find ways to parameterize them in terms of the larger-scale fields. Finding a parameterization that is both reliable and plausible to use in ocean models is not a simple task. Vertical mixing in the ocean is the combined result of many complex processes, and, in fact, mixing is one of the less known and less understood aspects of the oceanic circulation. In present models of the oceanic circulation, the many complex processes responsible for vertical mixing are often parameterized in an oversimplified manner. Yet, finding an adequate parameterization of vertical ocean mixing is crucial to the successful application of ocean models to climate studies. The results of general circulation models for quantities that are of particular interest to climate studies, such as the meridional heat flux carried by the ocean, are quite sensitive to the strength of the vertical mixing. We try to examine the difficulties in choosing an appropriate vertical mixing parameterization, and the methods that are available for validating different parameterizations by comparing model results to oceanographic data. First, some of the physical processes responsible for vertically mixing the ocean are briefly mentioned, and some possible approaches to the parameterization of these processes in oceanographic general circulation models are described in the following section. We then discuss the role of the vertical mixing in the physics of the large-scale ocean circulation, and examine methods of validating mixing parameterizations using large-scale ocean models.

Minimal modeling of the extratropical general circulation

NASA Technical Reports Server (NTRS)

O'Brien, Enda; Branscome, Lee E.

1989-01-01

The ability of low-order, two-layer models to reproduce basic features of the mid-latitude general circulation is investigated. Changes in model behavior with increased spectral resolution are examined in detail. Qualitatively correct time-mean heat and momentum balances are achieved in a beta-plane channel model which includes the first and third meridional modes. This minimal resolution also reproduces qualitatively realistic surface and upper-level winds and mean meridional circulations. Higher meridional resolution does not result in substantial changes in the latitudinal structure of the circulation. A qualitatively correct kinetic energy spectrum is produced when the resolution is high enough to include several linearly stable modes. A model with three zonal waves and the first three meridional modes has a reasonable energy spectrum and energy conversion cycle, while also satisfying heat and momentum budget requirements. This truncation reproduces the basic mechanisms and zonal circulation features that are obtained at higher resolution. The model performance improves gradually with higher resolution and is smoothly dependent on changes in external parameters.

36 CFR 910.18 - Vehicular circulation and storage systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CORPORATION GENERAL GUIDELINES AND UNIFORM STANDARDS FOR URBAN PLANNING AND DESIGN OF DEVELOPMENT WITHIN THE PENNSYLVANIA AVENUE DEVELOPMENT AREA Urban Planning and Design Concerns § 910.18 Vehicular circulation and...

Diagnostic Studies With GLA Fields

NASA Technical Reports Server (NTRS)

Salstein, David A.

1997-01-01

Assessments of the NASA Goddard Earth Observing System-1 Data Assimilation System (GEOS-1 DAS) regarding heating rates, energetics and angular momentum quantities were made. These diagnostics can be viewed as measures of climate variability. Comparisons with the NOAA/NCEP reanalysis system of momentum and energetics diagnostics are included. Water vapor and angular momentum are diagnosed in many models, including those of NASA, as part of the Atmospheric Model Intercomparison Project. Relevant preprints are included herein.

Selected translated abstracts of Russian-language climate-change publications. 4: General circulation models (in English;Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burtis, M.D.; Razuvaev, V.N.; Sivachok, S.G.

1996-10-01

This report presents English-translated abstracts of important Russian-language literature concerning general circulation models as they relate to climate change. Into addition to the bibliographic citations and abstracts translated into English, this report presents the original citations and abstracts in Russian. Author and title indexes are included to assist the reader in locating abstracts of particular interest.

High-resolution interpolation of climate scenarios for Canada derived from general circulation model simulations

Treesearch

D. T. Price; D. W. McKenney; L. A. Joyce; R. M. Siltanen; P. Papadopol; K. Lawrence

2011-01-01

Projections of future climate were selected for four well-established general circulation models (GCMs) forced by each of three greenhouse gas (GHG) emissions scenarios recommended by the Intergovernmental Panel on Climate Change (IPCC), namely scenarios A2, A1B, and B1 of the IPCC Special Report on Emissions Scenarios. Monthly data for the period 1961-2100 were...

The Numerical Studies Program for the Atmospheric General Circulation Experiment (AGCE) for Spacelab Flights

NASA Technical Reports Server (NTRS)

Fowlis, W. W. (Editor); Davis, M. H. (Editor)

1981-01-01

The atmospheric general circulation experiment (AGCE) numerical design for Spacelab flights was studied. A spherical baroclinic flow experiment which models the large scale circulations of the Earth's atmosphere was proposed. Gravity is simulated by a radial dielectric body force. The major objective of the AGCE is to study nonlinear baroclinic wave flows in spherical geometry. Numerical models must be developed which accurately predict the basic axisymmetric states and the stability of nonlinear baroclinic wave flows. A three dimensional, fully nonlinear, numerical model and the AGCE based on the complete set of equations is required. Progress in the AGCE numerical design studies program is reported.

Summer Study Program in Geophysical Fluid Dynamics 1989. General Circulation of the Oceans

DTIC Science & Technology

1989-11-01

Description of the Surface Circulation 2.2 A Description of the Interior Circulation 2.3 Formation Sites and Circulation of Deepwater Masses 2.4 Mode...and atmosphere, we have to follow basic laws of physics which lead us to try to solve a series of conservation equations, Mass : Dp*+ P() Du. - , ’ O.j...r~--~)(18) where,= vorticity 0 - 1 Vertically integrated mass conservation gives which leads to T.3) (19) Using the fact that Ro, ;<<I, the lowest

Circulation in the South China Sea during summer 2000 as obtained from observations and a generalized topography-following ocean model

NASA Astrophysics Data System (ADS)

Wang, Huiqun; Yuan, Yaochu; Guan, Weibing; Lou, Ruyun; Wang, Kangshan

2004-07-01

On the basis of the recently obtained hydrographic data in the South China Sea, the improved Princeton Ocean Model with a generalized topography-following coordinate system is used to study the circulation in the region during summer 2000. Several sensitivity experiments are carried out to achieve reasonable model parameters for the South China Sea (SCS). It is shown from the resting stratification experiments that the generalized topography-following coordinate scheme is better than the standard sigma grid scheme for reducing the pressure gradient errors. The combination of sea surface height anomaly derived from TOPEX/Poseidon and numerical results with both diagnostic and semidiagnostic simulations provides a consistent circulation pattern for the SCS in August, and the main circulation features can be summarized as follows: (1) There is a notable anticyclonic warm eddy southeast of Vietnam with a horizontal scale of ˜300 km, and there is a cyclonic cold eddy. The simultaneous existence of these cold and warm eddies is one of the important circulation characteristics in the SCS during summer 2000. (2) A secondary cold eddy is found east of Vietnam. (3) The northwestern part of the SCS is dominated by an anticyclonic circulation system. (4) There is also a secondary warm eddy southwest off the Luzon Island. (5) A cyclonic eddy is found west off the Borneo Island. (6) A western intensification phenomenon obviously occurs in the SCS. The dynamical mechanisms of the above-mentioned circulation pattern in the SCS are the interaction between the wind stress and bottom topography and the joint effect of baroclinicity and relief.

3D General Circulation Model of the Middle Atmosphere of Jupiter

NASA Astrophysics Data System (ADS)

Zube, Nicholas Gerard; Zhang, Xi; Li, Cheng; Le, Tianhao

2017-10-01

The characteristics of Jupiter’s large-scale stratospheric circulation remain largely unknown. Detailed distributions of temperature and photochemical species have been provided by recent observations [1], but have not yet been accurately reproduced by middle atmosphere general circulation models (GCM). Jupiter’s stratosphere and upper troposphere are influenced by radiative forcing from solar insolation and infrared cooling from hydrogen and hydrocarbons, as well as waves propagating from the underlying troposphere [2]. The relative significance of radiative and mechanical forcing on stratospheric circulation is still being debated [3]. Here we present a 3D GCM of Jupiter’s atmosphere with a correlated-k radiative transfer scheme. The simulation results are compared with observations. We analyze the impact of model parameters on the stratospheric temperature distribution and dynamical features. Finally, we discuss future tracer transport and gravity wave parameterization schemes that may be able to accurately simulate the middle atmosphere dynamics of Jupiter and other giant planets.[1] Kunde et al. 2004, Science 305, 1582.[2] Zhang et al. 2013a, EGU General Assembly, EGU2013-5797-2.[3] Conrath 1990, Icarus, 83, 255-281.

A Complex Use of the Materials Extracted from an Open-Cast Lignite Mine

NASA Astrophysics Data System (ADS)

Buryan, Petr; Bučko, Zdeněk; Mika, Petr

2014-12-01

The company Sokolovská uhelná, was the largest producer of city gas in the Czech Republic. After its substitution by natural gas the gasification technology became the basis of the production of electricity in the combine cycle power plant with total output 400 MW. For the possibility of gasification of liquid by- -products forming during the coal gasification a entrained-flow gasifier capable to process also alternative liquid fuels has been in installed. The concentrated waste gas with these sulphur compounds is conducted to the desulphurisation where the highly desired, pure, 96 % H2SO4 is produced. Briquettable brown coal is crushed, milled and dried and then it is passed into briquetting presses where briquettes, used mainly as a fuel in households, are pressed without binder in the punch under the pressure of 175 MPa. Fine brown coal dust (multidust) is commercially used for heat production in pulverized-coal burners. It forms not only during coal drying after separation on electrostatic separators, but it is also acquired by milling of dried coal in a vibratory bar mill. Slag from boilers of classical power plant, cinder form generators and ashes deposited at the dump are dehydrated and they are used as a quality bedding material during construction of communications in the mines of SUAS. Fly ash is used in building industry for partial substitution of cement in concrete. Flue gases after separation of fly ash are desulphurized by wet limestone method, where the main product is gypsum used, among others, in the building industry. Expanded clays from overburdens of coal seams, that are raw material for the production of "Liapor" artificial aggregate, are used heavily. This artificial aggregate is characterized by outstanding thermal and acoustic insulating properties. Przedsiębiorstwo Sokolovska uhelna jest największym producentem gazu miejskiego w Republice Czeskiej. Po jego zastąpieniu przez gaz ziemny, technologia gazyfikacji stała się podstawą do produkcji elektryczności w elektrowni o cyklu mieszanym o całkowitej mocy wyjściowej 400 MW. W celu umożliwienia gazyfikacji ciekłych produktów ubocznych gazyfikacji węgla, zainstalowano na drodze przepływu generator gazu, umożliwiający przetwarzanie alternatywnych paliw ciekłych. Skoncentrowany gaz odlotowy zawierający związki siarki odprowadzany jest do instalacji odsiarczającej, gdzie produkowany jest cenny produkt H2SO4, o wysokim stopniu czystości (96%). Węgiel brunatny nadający się do produkcji brykietów jest kruszony, mielony i suszony, następnie przechodzi przez proces brykietowania w odpowiednich prasach, gdzie formowane są brykiety, poprzez ich sprasowanie pod ciśnieniem 175 MPa. Brykiety takie wykorzystywane są powszechnie jako paliwo w gospodarstwach domowych. Drobnoziarniste pyły węgla brunatnego (paliwa pyłowe) wykorzystywane są na skalę komercyjną do produkcji ciepła w paleniskach pyłowych. Pyły węglowe powstają nie tylko w trakcie suszenia węgla po procesie oddzielania w separatorach elektrostatycznych, lecz także w procesie mielenia suszonego węgla w młynach wibracyjnych. Żużel z kotłów w konwencjonalnej elektrowni, popioły z generatorów oraz te osadzające się w instalacji podlegają wysuszeniu, następnie wykorzystywane są jako wysokiej jakości materiał na podłoże w różnorodnych instalacjach. Popioły lotne wykorzystywane są przemyśle budowlanym jako częściowe zamienniki cementu. Po oddzieleni popiołu lotnego, gazy wylotowe kierowane są do instalacji odsiarczania z wykorzystaniem technologii wilgotnego wapienia, w wyniku tego procesu powstaje gips, wykorzystywany, miedzy innymi, w przemyśle budowlanym. Glinki z warstw nadkładu nad pokładami węgla wykorzystywane są powszechnie jako surowiec do produkcji sztucznego kruszywa "Liapor', wykazującego wyjątkowe właściwości termiczne i dźwiękoizolacyjne.

Integrated and spectral energetics of the GLAS general circulation model

NASA Technical Reports Server (NTRS)

Tenenbaum, J.

1981-01-01

Integrated and spectral error energetics of the Goddard Laboratory for Atmospheric Sciences (GLAS) general circulation model are compared with observations for periods in January 1975, 1976, and 1977. For two cases the model shows significant skill in predicting integrated energetics quantities out to two weeks, and for all three cases, the integrated monthly mean energetics show qualitative improvements over previous versions of the model in eddy kinetic energy and barotropic conversions. Fundamental difficulties remain with leakage of energy to the stratospheric level. General circulation model spectral energetics predictions are compared with the corresponding observational spectra on a day by day basis. Eddy kinetic energy can be correct while significant errors occur in the kinetic energy of wavenumber three. Single wavenumber dominance in eddy kinetic energy and the correlation of spectral kinetic and potential energy are demonstrated.

Representation of Clear and Cloudy Boundary Layers in Climate Models. Chapter 14

NASA Technical Reports Server (NTRS)

Randall, D. A.; Shao, Q.; Branson, M.

1997-01-01

The atmospheric general circulation models which are being used as components of climate models rely on their boundary layer parameterizations to produce realistic simulations of the surface turbulent fluxes of sensible heat. moisture. and momentum: of the boundary-layer depth over which these fluxes converge: of boundary layer cloudiness: and of the interactions of the boundary layer with the deep convective clouds that grow upwards from it. Two current atmospheric general circulation models are used as examples to show how these requirements are being addressed: these are version 3 of the Community Climate Model. which has been developed at the U.S. National Center for Atmospheric Research. and the Colorado State University atmospheric general circulation model. The formulations and results of both models are discussed. Finally, areas for future research are suggested.

High resolution interpolation of climate scenarios for the conterminous USA and Alaska derived from general circulation model simulations

Treesearch

Linda A. Joyce; David T. Price; Daniel W. McKenney; R. Martin Siltanen; Pia Papadopol; Kevin Lawrence; David P. Coulson

2011-01-01

Projections of future climate were selected for four well-established general circulation models (GCM) forced by each of three greenhouse gas (GHG) emissions scenarios, namely A2, A1B, and B1 from the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES). Monthly data for the period 1961-2100 were downloaded mainly from the web...

Spectrum Analysis of Inertial and Subinertial Motions Based on Analyzed Winds and Wind-Driven Currents from a Primitive Equation General Ocean Circulation Model.

DTIC Science & Technology

1982-12-01

1Muter.Te Motions Based on Ana lyzed Winds and wind-driven December 1982 Currents from. a Primitive Squat ion General a.OW -love"*..* Oean Circulation...mew se"$ (comeS.... do oISN..u am ae~ 00do OWaor NUN Fourier and Rotary Spc , Analysis Modeled Inertial and Subinrtial Motion 4 Primitive Equation

Seasonal changes in the atmospheric heat balance simulated by the GISS general circulation model

NASA Technical Reports Server (NTRS)

Stone, P. H.; Chow, S.; Helfand, H. M.; Quirk, W. J.; Somerville, R. C. J.

1975-01-01

Tests of the ability of numerical general circulation models to simulate the atmosphere have focussed so far on simulations of the January climatology. These models generally present boundary conditions such as sea surface temperature, but this does not prevent testing their ability to simulate seasonal changes in atmospheric processes that accompany presented seasonal changes in boundary conditions. Experiments to simulate changes in the zonally averaged heat balance are discussed since many simplified models of climatic processes are based solely on this balance.

An investigation of anticyclonic circulation in the southern Gulf of Riga during the spring period

NASA Astrophysics Data System (ADS)

Soosaar, Edith; Maljutenko, Ilja; Raudsepp, Urmas; Elken, Jüri

2014-04-01

Previous studies of the gulf-type Region of Freshwater Influence (ROFI) have shown that circulation near the area of freshwater inflow sometimes becomes anticyclonic. Such a circulation is different from basic coastal ocean buoyancy-driven circulation where an anticyclonic bulge develops near the source and a coastal current is established along the right hand coast (in the northern hemisphere), resulting in the general cyclonic circulation. The spring (from March to June) circulation and spreading of river discharge water in the southern Gulf of Riga (GoR) in the Baltic Sea was analyzed based on the results of a 10-year simulation (1997-2006) using the General Estuarine Transport Model (GETM). Monthly mean currents in the upper layer of the GoR revealed a double gyre structure dominated either by an anticyclonic or cyclonic gyre in the near-head southeastern part and corresponding cyclonic/anticyclonic gyre in the near-mouth northwestern part of the gulf. Time series analysis of PCA and vorticity, calculated from velocity data and model sensitivity tests, showed that in spring the anticyclonic circulation in the upper layer of the southern GoR is driven primarily by the estuarine type density field. This anticyclonic circulation is enhanced by easterly winds but blocked or even reversed by westerly winds. The estuarine type density field is maintained by salt flux in the northwestern connection to the Baltic Proper and river discharge in the southern GoR.

An investigation of anticyclonic circulation in the southern Gulf of Riga during the spring period

NASA Astrophysics Data System (ADS)

Soosaar, Edith; Maljutenko, Ilja; Raudsepp, Urmas; Elken, Jüri

2015-04-01

Previous studies of the gulf-type Region of Freshwater Influence (ROFI) have shown that circulation near the area of freshwater inflow sometimes becomes anticyclonic. Such a circulation is different from basic coastal ocean buoyancy-driven circulation where an anticyclonic bulge develops near the source and a coastal current is established along the right hand coast (in the northern hemisphere), resulting in the general cyclonic circulation. The spring (from March to June) circulation and spreading of river discharge water in the southern Gulf of Riga (GoR) in the Baltic Sea was analyzed based on the results of a 10-year simulation (1997-2006) using the General Estuarine Transport Model (GETM). Monthly mean currents in the upper layer of the GoR revealed a double gyre structure dominated either by an anticyclonic or cyclonic gyre in the near-head southeastern part and corresponding cyclonic/anticyclonic gyre in the near-mouth northwestern part of the gulf. Time series analysis of PCA and vorticity, calculated from velocity data and model sensitivity tests, showed that in spring the anticyclonic circulation in the upper layer of the southern GoR is driven primarily by the estuarine type density field. This anticyclonic circulation is enhanced by easterly winds but blocked or even reversed by westerly winds. The estuarine type density field is maintained by salt flux in the northwestern connection to the Baltic Proper and river discharge in the southern GoR.

The puzzling Venusian polar atmospheric structure reproduced by a general circulation model

PubMed Central

Ando, Hiroki; Sugimoto, Norihiko; Takagi, Masahiro; Kashimura, Hiroki; Imamura, Takeshi; Matsuda, Yoshihisa

2016-01-01

Unlike the polar vortices observed in the Earth, Mars and Titan atmospheres, the observed Venus polar vortex is warmer than the midlatitudes at cloud-top levels (∼65 km). This warm polar vortex is zonally surrounded by a cold latitude band located at ∼60° latitude, which is a unique feature called ‘cold collar' in the Venus atmosphere. Although these structures have been observed in numerous previous observations, the formation mechanism is still unknown. Here we perform numerical simulations of the Venus atmospheric circulation using a general circulation model, and succeed in reproducing these puzzling features in close agreement with the observations. The cold collar and warm polar region are attributed to the residual mean meridional circulation enhanced by the thermal tide. The present results strongly suggest that the thermal tide is crucial for the structure of the Venus upper polar atmosphere at and above cloud levels. PMID:26832195

Two phase gap cooling of an electrical machine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shoykhet, Boris A.

2016-10-04

An electro-dynamic machine has a rotor and stator with a gap therebetween. The machine has a frame defining a hollow interior with end cavities on axially opposite ends of the frame. A gas circulating system has an inlet that supplies high pressure gas to the frame interior and an outlet to collect gas passing therethrough. A liquid coolant circulating system has an inlet that supplies coolant to the frame interior and an outlet that collects coolant passing therethrough. The coolant inlet and gas inlet are generally located on the frame in a manner to allow coolant from the coolant inletmore » to flow with gas from the gas inlet to the gap. The coolant outlet and gas outlet are generally located on the frame in a manner to allow the coolant to be separated from the gas with the separated coolant and gas collected for circulation through their respective circulating systems.« less

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats.

PubMed

Nagura, Nana; Komatsu, Jun; Iwase, Hideaki; Hosoda, Hiroshi; Ohbayashi, Osamu; Nagaoka, Isao; Kaneko, Kazuo

2015-05-01

The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts.

Effects of the combination of vitamin K and teriparatide on the bone metabolism in ovariectomized rats

PubMed Central

NAGURA, NANA; KOMATSU, JUN; IWASE, HIDEAKI; HOSODA, HIROSHI; OHBAYASHI, OSAMU; NAGAOKA, ISAO; KANEKO, KAZUO

2015-01-01

The purpose of the present study was to evaluate the combined effects of vitamin K (VK) and teriparatide (TPTD) on bone mineral density (BMD), mechanical strength and other parameters for bone metabolism using a rat ovariectomized osteoporosis model. Ovariectomized female Sprague-Dawley rats were administered with VK (an oral dose of 30 mg/kg/day), TPTD (a subcutaneous dose of 30 µg/kg, three times a week) or a combination for 8 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA; BMD and mechanical strength were measured by computed tomography and biomechanical testing, respectively at the femoral metaphysis. Additionally, histomorphometry was performed using the toluidine blue-stained coronal sections of distal femur. The combination of VK and TPTD clearly increased the serum levels of Gla-OC (a specific marker for bone formation) and osteoblast surface (the number of osteoblasts attaching with the surface of cancellous bone), compared to VK or TPTD alone. In addition, the combination of the two agents improved the BMD and bone strength of the femur in the ovariectomized rats, compared to VK or TPTD alone. Taken together, these findings suggest that the treatment with VK and TPTD may have a therapeutic advantage over VK or TPTD monotherapy for postmenopausal osteoporosis, possibly by enhancing the bone formation through the actions on OC and osteoblasts. PMID:26137225

Insights into the association of Gla-rich protein and osteoarthritis, novel splice variants and γ-carboxylation status.

PubMed

Rafael, Marta S; Cavaco, Sofia; Viegas, Carla S B; Santos, Sofia; Ramos, Acácio; Willems, Brecht A G; Herfs, Marjolein; Theuwissen, Elke; Vermeer, Cees; Simes, Dina C

2014-08-01

Gla-rich protein (GRP) is a vitamin K dependent protein, characterized by a high density of γ-carboxylated Glu residues, shown to accumulate in mouse and sturgeon cartilage and at sites of skin and vascular calcification in humans. Therefore, we investigated the involvement of GRP in pathological calcification in osteoarthritis (OA). Comparative analysis of GRP patterning at transcriptional and translational levels was performed between controls and OA patients. Using a RT-PCR strategy we unveiled two novel splice variants in human-GRP-F5 and F6-potentially characterized by the loss of full γ-carboxylation and secretion functional motifs. GRP-F1 is shown to be the predominant splice variant expressed in mouse and human adult tissues, particularly in OA cartilage, while an overexpressing human cell model points it as the major γ-carboxylated isoform. Using validated conformational antibodies detecting carboxylated or undercarboxylated GRP (c/uc GRP), we have demonstrated cGRP accumulation in controls, whereas ucGRP was the predominant form in OA-affected tissues, colocalizing at sites of ectopic calcification. Overall, our results indicate the predominance of GRP-F1, and a clear association of ucGRP with OA cartilage and synovial membrane. Levels of vitamin K should be further assessed in these patients to determine its potential therapeutic use as a supplement in OA treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Finite cohesion due to chain entanglement in polymer melts.

PubMed

Cheng, Shiwang; Lu, Yuyuan; Liu, Gengxin; Wang, Shi-Qing

2016-04-14

Three different types of experiments, quiescent stress relaxation, delayed rate-switching during stress relaxation, and elastic recovery after step strain, are carried out in this work to elucidate the existence of a finite cohesion barrier against free chain retraction in entangled polymers. Our experiments show that there is little hastened stress relaxation from step-wise shear up to γ = 0.7 and step-wise extension up to the stretching ratio λ = 1.5 at any time before or after the Rouse time. In contrast, a noticeable stress drop stemming from the built-in barrier-free chain retraction is predicted using the GLaMM model. In other words, the experiment reveals a threshold magnitude of step-wise deformation below which the stress relaxation follows identical dynamics whereas the GLaMM or Doi-Edwards model indicates a monotonic acceleration of the stress relaxation dynamics as a function of the magnitude of the step-wise deformation. Furthermore, a sudden application of startup extension during different stages of stress relaxation after a step-wise extension, i.e. the delayed rate-switching experiment, shows that the geometric condensation of entanglement strands in the cross-sectional area survives beyond the reptation time τd that is over 100 times the Rouse time τR. Our results point to the existence of a cohesion barrier that can prevent free chain retraction upon moderate deformation in well-entangled polymer melts.

Glassy-state stabilization of a dominant negative inhibitor anthrax vaccine containing aluminum hydroxide and glycopyranoside lipid A adjuvants.

PubMed

Hassett, Kimberly J; Vance, David J; Jain, Nishant K; Sahni, Neha; Rabia, Lilia A; Cousins, Megan C; Joshi, Sangeeta; Volkin, David B; Middaugh, C Russell; Mantis, Nicholas J; Carpenter, John F; Randolph, Theodore W

2015-02-01

During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA). Freeze-thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. Immunogenicity of liquid vaccines also decreased when stored at 40°C for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40°C. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40°C and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40°C were observed. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

The Feasibility of Xpert MTB/RIF Testing to Detect Rifampicin Resistance among Childhood Tuberculosis for Prevalence Surveys in Northern China.

PubMed

Lu, Jie; Li, Huimin; Dong, Fang; Shi, Jin; Yang, Hui; Han, Shujing; Chu, Ping; Zhao, Yanlin; Song, Wenqi; Guo, Yongli; Zhao, Shunying

2017-01-01

Drug resistance surveillance is crucial for control of drug-resistant tuberculosis (TB). However, limited data exists on the burden of drug-resistant TB in children. The goal of this work was to generate prevalence data regarding rifampicin- (RIF-) resistant childhood TB in northern China and to test the feasibility of Xpert for surveying pediatric TB drug resistance prevalence. We enrolled 362 clinically diagnosed childhood TB patients and collected sputum, gastric lavage aspirate (GLA), bronchoalveolar lavage fluid (BALF), and cerebral spinal fluid (CSF) samples. Xpert and solid culture were utilized to detect RIF resistance. The detection rate of Xpert-positive TB among new clinically diagnosed TB cases was 38.4% (139/362), significantly higher than that of solid culture-positive TB (16.3%, 59/362, P < 0.01). Notably, Xpert-positive rates differed significantly by sample type, with the highest positive rate for GLA (51.2%). The unit testing costs per RIF-resistant TB patient were $828.41 for solid culture and $761.86 for Xpert. Our data demonstrate that the prevalence of RIF resistance among childhood TB cases in our study (6.9%) is comparable to the national RIF resistance prevalence level of new cases (6.7%). In addition, Xpert is superior to the solid culture for RIF resistance survey in the childhood TB patients.

Energy utilization of induced pluripotent stem cell-derived cardiomyocyte in Fabry disease.

PubMed

Chou, Shih-Jie; Yu, Wen-Chung; Chang, Yuh-Lih; Chen, Wen-Yeh; Chang, Wei-Chao; Chien, Yueh; Yen, Jiin-Cherng; Liu, Yung-Yang; Chen, Shih-Jen; Wang, Chien-Ying; Chen, Yu-Han; Niu, Dau-Ming; Lin, Shing-Jong; Chen, Jaw-Wen; Chiou, Shih-Hwa; Leu, Hsin-Bang

2017-04-01

Fabry disease (FD) is a lysosomal storage disease in which glycosphingolipids (GB3) accumulate in organs of the human body, leading to idiopathic hypertrophic cardiomyopathy and target organ damage. Its pathophysiology is still poorly understood. We aimed to generate patient-specific induced pluripotent stem cells (iPSC) from FD patients presenting cardiomyopathy to determine whether the model could recapitulate key features of the disease phenotype and to investigate the energy metabolism in Fabry disease. Peripheral blood mononuclear cells from a 30-year-old Chinese man with a diagnosis of Fabry disease, GLA gene (IVS4+919G>A) mutation were reprogrammed into iPSCs and differentiated into iPSC-CMs and energy metabolism was analyzed in iPSC-CMs. The FD-iPSC-CMs recapitulated numerous aspects of the FD phenotype including reduced GLA activity, cellular hypertrophy, GB3 accumulation and impaired contractility. Decreased energy metabolism with energy utilization shift to glycolysis was observed, but the decreased energy metabolism was not modified by enzyme rescue replacement (ERT) in FD-iPSCs-CMs. This model provided a promising in vitro model for the investigation of the underlying disease mechanism and development of novel therapeutic strategies for FD. This potential remedy for enhancing the energetic network and utility efficiency warrants further study to identify novel therapies for the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Galactosidase Alpha p.A143T Variant Fabry Disease May Result in a Phenotype With Multifocal Microvascular Cerebral Involvement at a Young Age.

PubMed

Hauth, Lothar; Kerstens, Jeroen; Yperzeele, Laetitia; Eyskens, François; Parizel, Paul M; Willekens, Barbara

2018-01-01

A 16-year-old male presented with episodic headaches and a brain magnetic resonance imaging (MRI) that showed multifocal punctate to patchy white matter lesions. The diagnosis of Fabry disease (FD) was suggested upon the finding of significantly reduced plasma alpha-galactosidase A activity (0.62 µmol/L or 13% of normal; normal range ≥ 1.65 μmol/L) and genetic investigation confirmed the presence of a hemizygous missense variant in the galactosidase alpha (GLA) gene (p.A143T). Baseline assessment of other systemic involvement showed only a discrete proteinuria. FD is a rare lysosomal storage disorder. Genetic screening studies have revealed over 600 variants in the GLA gene. The p.A143T variant is a genetic variant of unknown significance, with its associated phenotype ranging from classical FD to healthy unaffected patients. Some authors, however, deem this variant non-pathogenic. We describe the case of a 16-year-old male with multifocal white matter lesions on brain MRI, who was diagnosed with FD and carried this genetic variant. The causative p.A143T mutation can be associated with a more severe subclinical phenotype than has been reported to date. Furthermore, a diagnosis of FD should be considered when finding asymptomatic cerebral white matter lesions in a young patient.

Development of imidazolinone herbicide tolerant borage (Borago officinalis L.).

PubMed

Song, Dongyan; Wu, Guohai; Vrinten, Patricia; Qiu, Xiao

2017-09-01

Borage (Borago officinalis) is an annual herb that produces a high level of gamma-linolenic acid (GLA) in its seed oil. Due to the recognized health benefits of GLA, borage is now commercially cultivated worldwide. However, an herbicide-tolerant variety for effective weed management has not yet been developed. Here we report the generation and characterization of ethyl methanesulfonate (EMS) induced borage mutant lines tolerant to the herbicide imidazolinone. An EMS-mutagenized borage population was generated by using a series of concentrations of EMS to treat mature borage seeds. Screening of the M2 and M3 borage plants using an herbicide treatment resulted in the identification of two imidazolinone-tolerant lines. Sequence analysis of two acetohydroxyacid synthase (AHAS) genes, AHAS1 and AHAS2, from the mutant (tolerant) and wild type (susceptible) borage plants showed that single nucleotide substitutions which resulted in amino acid changes occurred in AHAS1 and AHAS2, respectively in the two tolerant lines. A KASP marker was then developed to differentiate the homozygous susceptible, homozygous tolerant and heterozygous borage plants. An in vitro assay showed that homozygous tolerant borage carrying the AHAS1 mutation retained significantly higher AHAS activity than susceptible borage across different imazamox concentrations. A herbicide dose response test indicated that the line with the AHAS1 mutation could tolerate four times the normally used field concentration of "Solo" herbicide. Copyright © 2017. Published by Elsevier B.V.

Association between changes in visual acuity and vision-related quality of life in Japanese patients with low vision.

PubMed

Yanagisawa, Mieko; Kato, Satoshi; Kunimatsu, Shiho; Kobayashi, Megumi; Ochiai, Makiko

2011-01-01

To investigate the association between vision-related quality of life (VRQOL) and changes in visual acuity (VA). We examined the VA in 100 patients for > 1 year and evaluated the degree of its impact on VRQOL using the National Eye Institute Visual Function (VF) Questionnaire (VFQ-25; Japanese version). Before determining VFQ-25, we monitored the changes in VA in these patients for 1 year and classified them into the following two groups depending on VA changes. Patients exhibiting a decline of > 3 steps in VA, as assessed by the logarithm of the minimum angle of resolution scale, were placed in the 'decline' group (47.0%) and patients exhibiting no change in VA were placed in the 'no change' group (53.0%). We compared the VFQ-25 scores between both groups in all patients with glaucoma (GLA) and macular degeneration (MD). The total score of the decline was 34.9 ± 13.6 and that of the no change group was 44.6 ± 13.9: the difference in the scores between both groups was statistically significant (p = 0.006). Similar results were obtained for patients with GLA and MD (p = 0.007 and 0.003, respectively). VRQOL differed between patients with constant VA and those with reduced VA, even though VA values were equal at a certain time point. Copyright © 2010 S. Karger AG, Basel.

Theoretical and experimental design studies for the Atmospheric General Circulation Experiment

NASA Technical Reports Server (NTRS)

Fowlis, W. W.; Hathaway, D. H.; Miller, T. L.; Roberts, G. O.; Kopecky, K. J.

1985-01-01

The major criterion for the Atmospheric General Circulation Experiment (AGCE) design is that it be possible to realize strong baroclinic instability in the spherical configuration chosen. A configuration was selected in which a hemispherical shell of fluid is subjected to latitudinal temperature gradients on its spherical boundaries and the latitudinal boundaries are insulators. Work in the laboratory with a cylindrical version of this configuration revealed more instabilities than baroclinic instability. Since researchers fully expect these additional instabilities to appear in the spherical configuration also, they decided to continue the laboratory cylindrical annulus studies. Four flow regimes were identified: an axisymmetric Hadley circulation, boundary layer convection, baroclinic waves and deep thermal convection. Regime diagrams were prepared.

A January angular momentum balance in the OSU two-level atmospheric general circulation model

NASA Technical Reports Server (NTRS)

Kim, J.-W.; Grady, W.

1982-01-01

The present investigation is concerned with an analysis of the atmospheric angular momentum balance, based on the simulation data of the Oregon State University two-level atmospheric general circulation model (AGCM). An attempt is also made to gain an understanding of the involved processes. Preliminary results on the angular momentum and mass balance in the AGCM are shown. The basic equations are examined, and questions of turbulent momentum transfer are investigated. The methods of analysis are discussed, taking into account time-averaged balance equations, time and longitude-averaged balance equations, mean meridional circulation, the mean meridional balance of relative angular momentum, and standing and transient components of motion.

Renewed circulation scheme of the Baltic Sea - based on the 40-year simulation with GETM.

NASA Astrophysics Data System (ADS)

Maljutenko, Ilja; Raudsepp, Urmas

2015-04-01

The general circulation of the Baltic Sea has been characterized as cyclonic in all sub-basins based on numerous measurements and model simulations. From the long-term hydrodynamical simulation our model results have verified the general cyclonic circulation in the Baltic Proper and in the Gulf of Bothnia, but the Gulf of Finland and the Gulf of Riga have shown tendency to anticyclonic circulation. We have applied the General Estuarine Transport Model ( GETM ) for the period of 1966 - 2006 with a 1 nautical mile horizontal resolution and density adaptive bottom following vertical coordinates to make it possible to simulate horizontal and vertical density gradients with better precision. The atmospheric forcing from dynamically downscaled ERA40-HIRLAM and parametrized lateral boundary conditions are applied. Model simulation show close agreement with measurements conducted in the main monitoring stations in the BS during the simulation period. The geostrophic adjustment of density driven currents along with the upward salinity flux due to entrainment could explain the anticyclonic circulation and strong coastal current. Mean vertical velocities show that upward and downward movements are forming closed vertical circulation loops along the bottom slope of the Baltic Proper and the Gulf of Bothnia. The model has also reproduced patchy vertical movement across the BS with some distinctive areas of upward advective fluxes in the GoF along the thalweg. The distinctive areas of deepwater upwelling are also evident in the Gdansk Basin, western Gotland Basin, northern Gotland Basin and in the northen part of the Bothnia Sea.

Plausible Effect of Weather on Atlantic Meridional Overturning Circulation with a Coupled General Circulation Model

NASA Astrophysics Data System (ADS)

Liu, Zedong; Wan, Xiuquan

2018-04-01

The Atlantic meridional overturning circulation (AMOC) is a vital component of the global ocean circulation and the heat engine of the climate system. Through the use of a coupled general circulation model, this study examines the role of synoptic systems on the AMOC and presents evidence that internally generated high-frequency, synoptic-scale weather variability in the atmosphere could play a significant role in maintaining the overall strength and variability of the AMOC, thereby affecting climate variability and change. Results of a novel coupling technique show that the strength and variability of the AMOC are greatly reduced once the synoptic weather variability is suppressed in the coupled model. The strength and variability of the AMOC are closely linked to deep convection events at high latitudes, which could be strongly affected by the weather variability. Our results imply that synoptic weather systems are important in driving the AMOC and its variability. Thus, interactions between atmospheric weather variability and AMOC may be an important feedback mechanism of the global climate system and need to be taken into consideration in future climate change studies.

Interactions Between Ocean Circulation and Topography in Icy Worlds

NASA Astrophysics Data System (ADS)

Goodman, J. C.

2018-05-01

To what extent does topography at the water-rock interface control the general circulation patterns of icy world oceans? And contrariwise, to what extent does liquid flow control the topography at the ice-water interface (or interfaces)?

Use of Ocean Remote Sensing Data to Enhance Predictions with a Coupled General Circulation Model

NASA Technical Reports Server (NTRS)

Rienecker, Michele M.

1999-01-01

Surface height, sea surface temperature and surface wind observations from satellites have given a detailed time sequence of the initiation and evolution of the 1997/98 El Nino. The data have beet complementary to the subsurface TAO moored data in their spatial resolution and extent. The impact of satellite observations on seasonal prediction in the tropical Pacific using a coupled ocean-atmosphere general circulation model will be presented.

Near-inertial Wave Studies Using Historical Mooring Records and a High-Resolution General Circulation Model

DTIC Science & Technology

2009-09-30

Mooring Records and a High- Resolution General Circulation Model Harper Simmons School of Fisheries and Ocean Sciences 903 Koyukuk Drive Fairbanks AK...oceanographic community has been to develop a global internal wave prediction system analogous to those already in place for surface waves. Early steps have... Fisheries and Ocean Sciences,903 Koyukuk Drive,Fairbanks,AK,99775 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND

The role of earth radiation budget studies in climate and general circulation research

NASA Technical Reports Server (NTRS)

Ramanathan, V.

1987-01-01

The use of earth radiation budget (ERB) data for climate and general circulation research is studied. ERB measurements obtained in the 1960's and 1970's have provided data on planetary brightness, planetary global energy balances, the greenhouse effect, solar insolation, meridional heat transport by oceans and atmospheres, regional forcing, climate feedback processes, and the computation of albedo values in low latitudes. The role of clouds in governing climate, in influencing the general circulation, and in determining the sensitivity of climate to external perturbations needs to be researched; a procedure for analyzing the ERB data, which will address these problems, is described. The approach involves estimating the clear-sky fluxes from the high spatial resolution scanner measurement and defining a cloud radiative forcing; the global average of the sum of the solar and long-wave cloud forcing yields the net radiative effect of clouds on the climate.

Intercomparison and interpretation of climate feedback processes in 19 atmospheric general circulation models

NASA Technical Reports Server (NTRS)

Cess, R. D.; Potter, G. L.; Blanchet, J. P.; Boer, G. J.; Del Genio, A. D.

1990-01-01

The present study provides an intercomparison and interpretation of climate feedback processes in 19 atmospheric general circulation models. This intercomparison uses sea surface temperature change as a surrogate for climate change. The interpretation of cloud-climate interactions is given special attention. A roughly threefold variation in one measure of global climate sensitivity is found among the 19 models. The important conclusion is that most of this variation is attributable to differences in the models' depiction of cloud feedback, a result that emphasizes the need for improvements in the treatment of clouds in these models if they are ultimately to be used as reliable climate predictors. It is further emphazied that cloud feedback is the consequence of all interacting physical and dynamical processes in a general circulation model. The result of these processes is to produce changes in temperature, moisture distribution, and clouds which are integrated into the radiative response termed cloud feedback.

Parameterizing Gravity Waves and Understanding Their Impacts on Venus' Upper Atmosphere

NASA Technical Reports Server (NTRS)

Brecht, A. S.; Bougher, S. W.; Yigit, Erdal

2018-01-01

The complexity of Venus’ upper atmospheric circulation is still being investigated. Simulations of Venus’ upper atmosphere largely depend on the utility of Rayleigh Friction (RF) as a driver and necessary process to reproduce observations (i.e. temperature, density, nightglow emission). Currently, there are additional observations which provide more constraints to help characterize the driver(s) of the circulation. This work will largely focus on the impact parameterized gravity waves have on Venus’ upper atmosphere circulation within a three dimensional hydrodynamic model (Venus Thermospheric General Circulation Model).

A two-tier atmospheric circulation classification scheme for the European-North Atlantic region

NASA Astrophysics Data System (ADS)

Guentchev, Galina S.; Winkler, Julie A.

A two-tier classification of large-scale atmospheric circulation was developed for the European-North-Atlantic domain. The classification was constructed using a combination of principal components and k-means cluster analysis applied to reanalysis fields of mean sea-level pressure for 1951-2004. Separate classifications were developed for the winter, spring, summer, and fall seasons. For each season, the two classification tiers were identified independently, such that the definition of one tier does not depend on the other tier having already been defined. The first tier of the classification is comprised of supertype patterns. These broad-scale circulation classes are useful for generalized analyses such as investigations of the temporal trends in circulation frequency and persistence. The second, more detailed tier consists of circulation types and is useful for numerous applied research questions regarding the relationships between large-scale circulation and local and regional climate. Three to five supertypes and up to 19 circulation types were identified for each season. An intuitive nomenclature scheme based on the physical entities (i.e., anomaly centers) which dominate the specific patterns was used to label each of the supertypes and types. Two example applications illustrate the potential usefulness of a two-tier classification. In the first application, the temporal variability of the supertypes was evaluated. In general, the frequency and persistence of supertypes dominated by anticyclonic circulation increased during the study period, whereas the supertypes dominated by cyclonic features decreased in frequency and persistence. The usefulness of the derived circulation types was exemplified by an analysis of the circulation associated with heat waves and cold spells reported at several cities in Bulgaria. These extreme temperature events were found to occur with a small number of circulation types, a finding that can be helpful in understanding past variability and projecting future changes in the occurrence of extreme weather and climate events.

An Oceanic General Circulation Model (OGCM) investigation of the Red Sea circulation: 2. Three-dimensional circulation in the Red Sea

NASA Astrophysics Data System (ADS)

Sofianos, Sarantis S.; Johns, William E.

2003-03-01

The three-dimensional circulation of the Red Sea is studied using a set of Miami Isopycnic Coordinate Ocean Model (MICOM) simulations. The model performance is tested against the few available observations in the basin and shows generally good agreement with the main observed features of the circulation. The main findings of this analysis include an intensification of the along-axis flow toward the coasts, with a transition from western intensified boundary flow in the south to eastern intensified flow in the north, and a series of strong seasonal or permanent eddy-like features. Model experiments conducted with different forcing fields (wind-stress forcing only, surface buoyancy forcing only, or both forcings combined) showed that the circulation produced by the buoyancy forcing is stronger overall and dominates the wind-driven part of the circulation. The main circulation pattern is related to the seasonal buoyancy flux (mostly due to the evaporation), which causes the density to increase northward in the basin and produces a northward surface pressure gradient associated with the downward sloping of the sea surface. The response of the eastern boundary to the associated mean cross-basin geostrophic current depends on the stratification and β-effect. In the northern part of the basin this results in an eastward intensification of the northward surface flow associated with the presence of Kelvin waves while in the south the traditional westward intensification due to Rossby waves takes place. The most prominent gyre circulation pattern occurs in the north where a permanent cyclonic gyre is present that is involved in the formation of Red Sea Outflow Water (RSOW). Beneath the surface boundary currents are similarly intensified southward undercurrents that carry the RSOW to the sill to flow out of the basin into the Indian Ocean.

Eddy Resolving Global Ocean Prediction including Tides

DTIC Science & Technology

2013-09-30

atlantic meridional overturning circulation in the subpolar North Atlantic . Journal of Geophysical Research vol 118, doi:10.1002/jgrc,20065. [published, refereed] ...global ocean circulation model was examined using results from years 2005-2009 of a seven and a half year 1/12.5° global simulation that resolves...internal tides, along with barotropic tides and the eddying general circulation . We examined tidal amplitudes computed using 18 183-day windows that

Regional climates in the GISS general circulation model: Surface air temperature

NASA Technical Reports Server (NTRS)

Hewitson, Bruce

1994-01-01

One of the more viable research techniques into global climate change for the purpose of understanding the consequent environmental impacts is based on the use of general circulation models (GCMs). However, GCMs are currently unable to reliably predict the regional climate change resulting from global warming, and it is at the regional scale that predictions are required for understanding human and environmental responses. Regional climates in the extratropics are in large part governed by the synoptic-scale circulation and the feasibility of using this interscale relationship is explored to provide a way of moving to grid cell and sub-grid cell scales in the model. The relationships between the daily circulation systems and surface air temperature for points across the continental United States are first developed in a quantitative form using a multivariate index based on principal components analysis (PCA) of the surface circulation. These relationships are then validated by predicting daily temperature using observed circulation and comparing the predicted values with the observed temperatures. The relationships predict surface temperature accurately over the major portion of the country in winter, and for half the country in summer. These relationships are then applied to the surface synoptic circulation of the Goddard Institute for Space Studies (GISS) GCM control run, and a set of surface grid cell temperatures are generated. These temperatures, based on the larger-scale validated circulation, may now be used with greater confidence at the regional scale. The generated temperatures are compared to those of the model and show that the model has regional errors of up to 10 C in individual grid cells.

Cloud Feedback in Atmospheric General Circulation Models: An Update

NASA Technical Reports Server (NTRS)

Cess, R. D.; Zhang, M. H.; Ingram, W. J.; Potter, G. L.; Alekseev, V.; Barker, H. W.; Cohen-Solal, E.; Colman, R. A.; Dazlich, D. A.; DelGenio, A. D.;

Adaptation of a general circulation model to ocean dynamics

NASA Technical Reports Server (NTRS)

Turner, R. E.; Rees, T. H.; Woodbury, G. E.

1976-01-01

A primitive-variable general circulation model of the ocean was formulated in which fast external gravity waves are suppressed with rigid-lid surface constraint pressires which also provide a means for simulating the effects of large-scale free-surface topography. The surface pressure method is simpler to apply than the conventional stream function models, and the resulting model can be applied to both global ocean and limited region situations. Strengths and weaknesses of the model are also presented.

Concurrent Simulation of the Eddying General Circulation and Tides in a Global Ocean Model

DTIC Science & Technology

2010-01-01

Eddying General Circulation and Tides in a Global Ocean Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 0602435N 6...STATEMENT Approved for public release, distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT This paper presents a five-year global ...running 25-h average to approximately separate tidal and non-tidal components of the near-bottom flow. In contrast to earlier high-resolution global

Derivation of revised formulae for eddy viscous forces used in the ocean general circulation model

NASA Technical Reports Server (NTRS)

Chou, Ru Ling

1988-01-01

Presented is a re-derivation of the eddy viscous dissipation tensor commonly used in present oceanographic general circulation models. When isotropy is imposed, the currently-used form of the tensor fails to return to the laplacian operator. In this paper, the source of this error is identified in a consistent derivation of the tensor in both rectangular and earth spherical coordinates, and the correct form of the eddy viscous tensor is presented.

Impact of lakes and wetlands on present and future boreal climate

NASA Astrophysics Data System (ADS)

Poutou, E.; Krinner, G.; Genthon, C.

2002-12-01

Impact of lakes and wetlands on present and future boreal climate The role of lakes and wetlands in present-day high latitude climate is quantified using a general circulation model of the atmosphere. The atmospheric model includes a lake module which is presented and validated. Seasonal and spatial wetland distribution is calculated as a function of the hydrological budget of the wetlands themselves and of continental soil whose runoff feeds them. Wetland extent is simulated and discussed both in simulations forced by observed climate and in general circulation model simulations. In off-line simulations, forced by ECMWF reanalyses, the lake model simulates correctly observed lake ice durations, while the wetland extent is somewhat underestimated in the boreal regions. Coupled to the general circulation model, the lake model yields satisfying ice durations, although the climate model biases have impacts on the modeled lake ice conditions. Boreal wetland extents are overestimated in the general circulation model as simulated precipitation is too high. The impact of inundated surfaces on the simulated climate is strongest in summer when these surfaces are ice-free. Wetlands seem to play a more important role than lakes in cooling the boreal regions in summer and in humidifying the atmosphere. The role of lakes and wetlands in future climate change is evaluated by analyzing simulations of present and future climate with and without prescribed inland water bodies.

Genetic manipulation of gamma-linolenic acid (GLA) synthesis in a commercial variety of evening primrose (Oenothera sp.).

PubMed

de Gyves, Emilio Mendoza; Sparks, Caroline A; Sayanova, Olga; Lazzeri, Paul; Napier, Johnathan A; Jones, Huw D

2004-07-01

A robust Agrobacterium-mediated transformation procedure was developed for Rigel, a commercial cultivar of evening primrose, and used to deliver a cDNA encoding a Delta(6)-desaturase from borage under the control of a cauliflower mosaic virus (CaMV) 35S promoter. Analysis of the transformed plants demonstrated an altered profile of polyunsaturated fatty acids, with an increase in gamma-linolenic acid and octadecatetraenoic acid in leaf tissues when compared with control lines.

TOVS Satellite Soundings of the ERICA IOP-2 Cyclone.

DTIC Science & Technology

1990-06-01

5 E. CO-MPA RI SONS B3ETWEEN THE RET:]RIEVA’.%L. ME-hODlS........... 6 Ill. BACKGROUND)..............................................S A...11 1. Goddard Laboratory for Atinosrheres (GL.A) physical retrieval........I11 2. I~jependeClC of thc first gues’s on the G LA physicil retrie...thank my wif’e. Jennifer, for her loving support and en1- couraczement to hielp me finish this thesis on time, and my son , Joseph. for providing the

Impact of moisture variations on the circulation of the south-west monsoon

NASA Astrophysics Data System (ADS)

Kishtawal, C. M.; Pal, P. K.; Narayanan, M. S.; Manna, S. K.; Sharma, O. P.; Agarwal, Sangeeta; Upadhyaya, H. C.

1993-12-01

The impact of moisture anomalies on the circulation of the south-west Indian monsoon has been studied with a general circulation model. Newtonian relaxation is adopted to subject the model atmosphere under sustained moisture anomalies. The impact of negative anomalies of moisture was seen as a divergent circulation anomaly, while the positive anomaly was a stronger convergent anomaly. Although the humidity fields display a resilient behaviour, and relax back to normal patterns 1-2 days after the forcing terms in humidity are withdrawn, the circulation anomalies created by the moisture variation keeps growing. A feedback between positive moisture anomalies and low level convergence exists, which is terminated in the absence of external forcings.

Atmospheric dynamics over Europe during the Younger Dryas revealed by palaeoglaciers.

NASA Astrophysics Data System (ADS)

Rea, Brice; Pellitero, Ramon; Spagnolo, Matteo; Hughes, Philip; Braithwaite, Roger; Renssen, Hans; Ivy-Ochs, Susan; Ribolini, Adriano; Bakke, Jostein; Lukas, Sven

2017-04-01

A dataset of 120 palaeoglaciers ranging from Morocco in the south to Svalbard in the north and from Ireland in the west to Turkey in the east, has been assembled from the literature. A robust quality control on the chronology was undertaken and, when derived from cosmogenic nuclides, ages were recalculated using the most up-to-date production rates. All the reconstructed glaciers date to the Younger Dryas. Frontal moraines/limits were used to initiate the palaeoglacier reconstructions using GlaRe, a GIS tool which generates an equilibrium profile ice surface along a single flowline and extrapolates this to out to a 3D ice surface. From the resulting glacier surfaces palaeo-ELAs were calculated within the GIS. Where multiple glaciers were reconstructed within in a region, a single ELA value was generated. Results show that ELAs decrease with latitude but have a more complex pattern with longitude. A database of 121 sites, spanning the same geographical range as the palaeoglaciers, was compiled for Younger Dryas temperature, determined from palaeoproxies, for example pollen, diatoms, coleoptera, chironimids etc. These proxy data were merged and interpolated to generate maps of average temperature for the warmest and coldest months and annual average temperature. Results show that, in general, temperature decreases with latitude. Temperature at the palaeo-ELAs were determined from the temperature maps using a lapse rate of 0.65°C/100m and the precipitation required for equilibrium was calculated. Positive precipitation anomalies are found along much of the western seaboard of Europe, with the most striking positive anomalies present in the eastern Mediterranean. Negative precipitation anomalies appear on the northern side of the Alps. This pattern is interpreted to represent a southward displaced polar frontal jet stream with a concomitant track of Atlantic mid-latitude depressions, leading to more frequent incursions of low pressure systems especially over the relatively warm eastern Mediterranean, enhancing cyclogenesis. This is similar to the modern Scandinavia (SCAND) pattern which, in its positive phase, is characterised by a high pressure anomaly over Fennoscandia and western Russia, negative pressure anomalies around the Iberian Peninsula and enhanced cyclogenesis in the central and eastern Mediterranean. During the YD the Fennoscandian Ice Sheet and permafrost across much of northern continental Europe and Russia would have generated a high pressure region leading to a persistent, enhanced SCAND circulation.

Tropical Cyclone Footprint in the Ocean Mixed Layer Observed by Argo in the Northwest Pacific

DTIC Science & Technology

2014-10-25

668. Hu, A., and G. A. Meehl (2009), Effect of the Atlantic hurricanes on the oceanic meridional overturning circulation and heat transport, Geo...atmospheric circulation [Hart et al., 2007]. Several studies, based on observations and modeling, suggest that TC-induced energy input and mixing may play...an important role in climate variability through regulating the oceanic general circulation and its variability [e.g., Emanuel, 2001; Sriver and Huber

Effects of Small-Scale Bathymetric Roughness on the Global Internal Wave Field

DTIC Science & Technology

2008-09-30

Navy. Much of the interest stems from the suggestion by Munk and Wunsch (1998) that the strength of the meridional overturning circulation is controlled... meridional overturning circulation . Journal of Physical Oceanography 32, 3578-3595. St. Laurent, L.C., 1999. Diapycnal advection by double diffusion...waves generated by flows over the rough seafloor. On the time scales of internal waves, mesoscale eddies and the general circulation can be regarded as

Tropical Pacific moisture variability: Its detection, synoptic structure and consequences in the general circulation

NASA Technical Reports Server (NTRS)

Mcguirk, James P.

1990-01-01

Satellite data analysis tools are developed and implemented for the diagnosis of atmospheric circulation systems over the tropical Pacific Ocean. The tools include statistical multi-variate procedures, a multi-spectral radiative transfer model, and the global spectral forecast model at NMC. Data include in-situ observations; satellite observations from VAS (moisture, infrared and visible) NOAA polar orbiters (including Tiros Operational Satellite System (TOVS) multi-channel sounding data and OLR grids) and scanning multichannel microwave radiometer (SMMR); and European Centre for Medium Weather Forecasts (ECHMWF) analyses. A primary goal is a better understanding of the relation between synoptic structures of the area, particularly tropical plumes, and the general circulation, especially the Hadley circulation. A second goal is the definition of the quantitative structure and behavior of all Pacific tropical synoptic systems. Finally, strategies are examined for extracting new and additional information from existing satellite observations. Although moisture structure is emphasized, thermal patterns are also analyzed. Both horizontal and vertical structures are studied and objective quantitative results are emphasized.

Regional climates in the GISS global circulation model - Synoptic-scale circulation

NASA Technical Reports Server (NTRS)

Hewitson, B.; Crane, R. G.

1992-01-01

A major weakness of current general circulation models (GCMs) is their perceived inability to predict reliably the regional consequences of a global-scale change, and it is these regional-scale predictions that are necessary for studies of human-environmental response. For large areas of the extratropics, the local climate is controlled by the synoptic-scale atmospheric circulation, and it is the purpose of this paper to evaluate the synoptic-scale circulation of the Goddard Institute for Space Studies (GISS) GCM. A methodology for validating the daily synoptic circulation using Principal Component Analysis is described, and the methodology is then applied to the GCM simulation of sea level pressure over the continental United States (excluding Alaska). The analysis demonstrates that the GISS 4 x 5 deg GCM Model II effectively simulates the synoptic-scale atmospheric circulation over the United States. The modes of variance describing the atmospheric circulation of the model are comparable to those found in the observed data, and these modes explain similar amounts of variance in their respective datasets. The temporal behavior of these circulation modes in the synoptic time frame are also comparable.

Near-inertial Wave Studies using Historical Mooring Records and a High-Resolution General Circulation Model

DTIC Science & Technology

2009-01-01

Mooring Records and a High- Resolution General Circulation Model Harper Simmons School of Fisheries and Ocean Sciences 903 Koyukuk Drive Fairbanks AK...oceanographic community has been to develop a global internal wave prediction system analogous to those already in place for surface waves. Early steps have...AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) School of Fisheries and Ocean

Land surface hydrology parameterization for atmospheric general circulation models including subgrid scale spatial variability

NASA Technical Reports Server (NTRS)

Entekhabi, D.; Eagleson, P. S.

1989-01-01

Parameterizations are developed for the representation of subgrid hydrologic processes in atmospheric general circulation models. Reasonable a priori probability density functions of the spatial variability of soil moisture and of precipitation are introduced. These are used in conjunction with the deterministic equations describing basic soil moisture physics to derive expressions for the hydrologic processes that include subgrid scale variation in parameters. The major model sensitivities to soil type and to climatic forcing are explored.

A Weak Constraint 4D-Var Assimilation System for the Navy Coastal Model Using the Representer Method

DTIC Science & Technology

2013-01-01

the help of the Parametric Fortrai compiler (PFC), Erwig et al. 2007 . Some general circulation models of the complexity of NCOM have seen 1 similar...the Mir general circulation model (MITgcm, Marotzke et al. 1999) also used in the ECCO consortium assimilation experiments ( Stammer et al. 2002...using the« inverse Regional Ocean Modeling System (IROMS, Di Lorenzo et al. 2007 ) with horizontal resolutions of 10 and 30km. The CCS is a large

Technical report series on global modeling and data assimilation. Volume 1: Documentation of the Goddard Earth Observing System (GEOS) General Circulation Model, version 1

NASA Technical Reports Server (NTRS)

Suarez, Max J. (Editor); Takacs, Lawrence L.; Molod, Andrea; Wang, Tina

1994-01-01

This technical report documents Version 1 of the Goddard Earth Observing System (GEOS) General Circulation Model (GCM). The GEOS-1 GCM is being used by NASA's Data Assimilation Office (DAO) to produce multiyear data sets for climate research. This report provides a documentation of the model components used in the GEOS-1 GCM, a complete description of model diagnostics available, and a User's Guide to facilitate GEOS-1 GCM experiments.

Biogeophysical consequences of a tropical deforestation scenario: A GCM simulation study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sud, Y.C.; Lau, W.K.M.; Walker, G.K.

1996-12-01

Two 3-year (1979-1982) integrations were carried out with a version of the GLA GCM that contains the Simple Biosphere Model (SiB) for simulating land-atmosphere interactions. The control case used the usual SiB vegetation cover (comprising 12 vegetation types), while its twin, the deforestation case, imposed a scenario in which all tropical rainforests were entirely replaced by grassland. Except for this difference, all other initial and prescribed boundary conditions were kept identical in both integrations. An intercomparison of the integrations shows that tropical: deforestation decreases evapotranspiration and increases land surface outgoing longwave radiation and sensible heat flux, thereby warming and dryingmore » the planetary boundary layer. This happens despite the reduced absorption of solar radiation due to higher surface albedo of the deforested land. Produces significant and robust local as well as global climate changes. The local effect includes significant changes (mostly reductions) in precipitation and diabatic heating, while the large-scale effect is to weaken the Hadley circulation but invigorate the southern Ferrel cell, drawing larger air mass from the indirect polar cells. Decreases the surface stress (drag force) owing to reduced surface roughness of deforested land, which in turn intensifies winds in the planetary boundary layer, thereby affecting the dynamic structure of moisture convergence. The simulated surface winds are about 70% stronger and are accompanied by significant changes in the power spectrum of the annual cycle of surface and PBL winds and precipitation. Our results broadly confirm several findings of recent tropical deforestation simulation experiments. In addition, some global-scale climatic influences of deforestation not identified in earlier studies are delineated. 57 refs., 10 figs., 3 tabs.« less

Oxidative Burst of Circulating Neutrophils Following Traumatic Brain Injury in Human

PubMed Central

Liao, Yiliu; Liu, Peng; Guo, Fangyuan; Zhang, Zhi-Yuan; Zhang, Zhiren

2013-01-01

Besides secondary injury at the lesional site, Traumatic brain injury (TBI) can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91phox) in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected organs and the injured brain from the secondary damage. PMID:23894384

Idealised modelling of ocean circulation driven by conductive and hydrothermal fluxes at the seabed

NASA Astrophysics Data System (ADS)

Barnes, Jowan M.; Morales Maqueda, Miguel A.; Polton, Jeff A.; Megann, Alex P.

2018-02-01

Geothermal heating is increasingly recognised as an important factor affecting ocean circulation, with modelling studies suggesting that this heat source could lead to first-order changes in the formation rate of Antarctic Bottom Water, as well as a significant warming effect in the abyssal ocean. Where it has been represented in numerical models, however, the geothermal heat flux into the ocean is generally treated as an entirely conductive flux, despite an estimated one third of the global geothermal flux being introduced to the ocean via hydrothermal sources. A modelling study is presented which investigates the sensitivity of the geothermally forced circulation to the way heat is supplied to the abyssal ocean. An analytical two-dimensional model of the circulation is described, which demonstrates the effects of a volume flux through the ocean bed. A simulation using the NEMO numerical general circulation model in an idealised domain is then used to partition a heat flux between conductive and hydrothermal sources and explicitly test the sensitivity of the circulation to the formulation of the abyssal heat flux. Our simulations suggest that representing the hydrothermal flux as a mass exchange indeed changes the heat distribution in the abyssal ocean, increasing the advective heat transport from the abyss by up to 35% compared to conductive heat sources. Consequently, we suggest that the inclusion of hydrothermal fluxes can be an important addition to course-resolution ocean models.

Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC).

PubMed

Shea, M Kyla; Booth, Sarah L; Weiner, Daniel E; Brinkley, Tina E; Kanaya, Alka M; Murphy, Rachel A; Simonsick, Eleanor M; Wassel, Christina L; Vermeer, Cees; Kritchevsky, Stephen B

2017-05-01

Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk. Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status. Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms. Results: Neither low plasma phylloquinone (<0.2 nmol/L) nor elevated (dp)ucMGP (≥574 pmol/L) was significantly associated with incident CVD [respective HRs (95% CIs): 1.27 (0.75, 2.13) and 1.02 (0.72, 1.45)]. In participants treated for hypertension ( n = 489; 135 events), low plasma phylloquinone was associated with higher CVD risk overall (HR: 2.94; 95% CI: 1.41, 6.13). In those with untreated hypertension ( n = 153; 48 events) and without hypertension ( n = 418; 92 events), low plasma phylloquinone was not associated with incident CVD. The association between high (dp)ucMGP did not differ by hypertension treatment status ( P -interaction = 0.72). Conclusions: Vitamin K status was not significantly associated with CVD risk overall, but low plasma phylloquinone was associated with a higher CVD risk in older adults treated for hypertension. Additional evidence from larger clinical studies is needed to clarify the importance of vitamin K to CVD in persons treated for hypertension, a segment of the population at high risk of clinical CVD events. © 2017 American Society for Nutrition.

Simultaneous generation of aptamers to multiple gamma-carboxyglutamic acid proteins from a focused aptamer library using DeSELEX and convergent selection.

PubMed

Layzer, Juliana M; Sullenger, Bruce A

2007-01-01

By using the in vitro selection method SELEX against the complex mixture of GLA proteins and utilizing methods to deconvolute the resulting ligands, we were able to successfully generate 2'-ribo purine, 2'-fluoro pyrimidine aptamers to various individual targets in the GLA protein proteome that ranged in concentration from 10 nM to 1.4 microM in plasma. Perhaps not unexpectedly, the majority of the aptamers isolated following SELEX bind the most abundant protein in the mixture, prothrombin (FII), with high affinity. We show that by deselecting the dominant prothrombin aptamer the selection can be redirected. By using this DeSELEX approach, we were able to shift the selection toward other sequences and to less abundant protein targets and obtained an aptamer to Factor IX (FIX). We also demonstrate that by using an RNA library that is focused around a proteome, purified protein targets can then be used to rapidly generate aptamers to the protein targets that are rare in the initial mixture such as Factor VII (FVII) and Factor X (FX). Moreover, for all four proteins targeted (FII, FVII, FIX, and FX), aptamers were identified that could inhibit the individual protein's activitity in coagulation assays. Thus, by applying the concepts of DeSELEX and focused library selection, aptamers specific for any protein in a particular proteome can theoretically be generated, even when the proteins in the mixture are present at very different concentrations.

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.

PubMed

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-11-05

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells.

A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites

PubMed Central

Haque, Jamil A.; McDonald, Matthew G.; Kulman, John D.

2014-01-01

Warfarin and other 4-hydroxycoumarins inhibit vitamin K epoxide reductase (VKOR) by depleting reduced vitamin K that is required for posttranslational modification of vitamin K–dependent clotting factors. In vitro prediction of the in vivo potency of vitamin K antagonists is complicated by the complex multicomponent nature of the vitamin K cycle. Here we describe a sensitive assay that enables quantitative analysis of γ-glutamyl carboxylation and its antagonism in live cells. We engineered a human embryonic kidney (HEK) 293–derived cell line (HEK 293-C3) to express a chimeric protein (F9CH) comprising the Gla domain of factor IX fused to the transmembrane and cytoplasmic regions of proline-rich Gla protein 2. Maximal γ-glutamyl carboxylation of F9CH required vitamin K supplementation, and was dose-dependently inhibited by racemic warfarin at a physiologically relevant concentration. Cellular γ-glutamyl carboxylation also exhibited differential VKOR inhibition by warfarin enantiomers (S > R) consistent with their in vivo potencies. We further analyzed the structure-activity relationship for inhibition of γ-glutamyl carboxylation by warfarin metabolites, observing tolerance to phenolic substitution at the C-5 and especially C-6, but not C-7 or C-8, positions on the 4-hydroxycoumarin nucleus. After correction for in vivo concentration and protein binding, 10-hydroxywarfarin and warfarin alcohols were predicted to be the most potent inhibitory metabolites in vivo. PMID:24297869

Essential fatty acids supplementation in different-stage atopic dogs fed on a controlled diet.

PubMed

Abba, C; Mussa, P P; Vercelli, A; Raviri, G

2005-01-01

The aim of this trial was to evaluate the effects of polyunsaturated fatty acid (PUFA) supplementation in different-stages atopic dogs fed on a controlled diet. Twenty-two non-seasonal atopic dogs of different breeds and ages were included in the 2-month trial. All the patients were given an essential fatty acid (EFA) supplementation [17 mg/kg eicosapentaenoic acid (EPA) + 5 mg/kg docosahexaenoic acid (DHA) + 35 mg/kg gammalinolenic acid (GLA)], the global (diet + supplementation) omega-6 to omega-3 ratio was 5.5-1. Two groups of dogs were considered: group A 'pre-immunotherapy' (15 cases) included dogs with early stages atopy, which had not been submitted to any treatment yet; group B 'post-immunotherapy' (seven cases) included dogs with chronic atopy immunotherapy non-responsive. Clinical evaluations were performed at the beginning, on day 30 and at the end of the trial. Blood serum fatty acids profile was determined at the beginning and at the end of the study. Better clinical results were obtained in group A, a great difference was found between the two groups on pruritus score. Serum arachidonic acid (AA) was significantly lower at the end of the trial in group A while GLA was significantly higher in group B. We hypothesized that different-stages atopic dogs could have different response to EFA supplementation, maybe because of a different fatty acids metabolism. Early stages cases seem to be more responsive to EFA supplementation.

Segmentation and classification of colon glands with deep convolutional neural networks and total variation regularization.

PubMed

Kainz, Philipp; Pfeiffer, Michael; Urschler, Martin

2017-01-01

Segmentation of histopathology sections is a necessary preprocessing step for digital pathology. Due to the large variability of biological tissue, machine learning techniques have shown superior performance over conventional image processing methods. Here we present our deep neural network-based approach for segmentation and classification of glands in tissue of benign and malignant colorectal cancer, which was developed to participate in the GlaS@MICCAI2015 colon gland segmentation challenge. We use two distinct deep convolutional neural networks (CNN) for pixel-wise classification of Hematoxylin-Eosin stained images. While the first classifier separates glands from background, the second classifier identifies gland-separating structures. In a subsequent step, a figure-ground segmentation based on weighted total variation produces the final segmentation result by regularizing the CNN predictions. We present both quantitative and qualitative segmentation results on the recently released and publicly available Warwick-QU colon adenocarcinoma dataset associated with the GlaS@MICCAI2015 challenge and compare our approach to the simultaneously developed other approaches that participated in the same challenge. On two test sets, we demonstrate our segmentation performance and show that we achieve a tissue classification accuracy of 98% and 95%, making use of the inherent capability of our system to distinguish between benign and malignant tissue. Our results show that deep learning approaches can yield highly accurate and reproducible results for biomedical image analysis, with the potential to significantly improve the quality and speed of medical diagnoses.

Segmentation and classification of colon glands with deep convolutional neural networks and total variation regularization

PubMed Central

Kainz, Philipp; Pfeiffer, Michael

2017-01-01

Segmentation of histopathology sections is a necessary preprocessing step for digital pathology. Due to the large variability of biological tissue, machine learning techniques have shown superior performance over conventional image processing methods. Here we present our deep neural network-based approach for segmentation and classification of glands in tissue of benign and malignant colorectal cancer, which was developed to participate in the GlaS@MICCAI2015 colon gland segmentation challenge. We use two distinct deep convolutional neural networks (CNN) for pixel-wise classification of Hematoxylin-Eosin stained images. While the first classifier separates glands from background, the second classifier identifies gland-separating structures. In a subsequent step, a figure-ground segmentation based on weighted total variation produces the final segmentation result by regularizing the CNN predictions. We present both quantitative and qualitative segmentation results on the recently released and publicly available Warwick-QU colon adenocarcinoma dataset associated with the GlaS@MICCAI2015 challenge and compare our approach to the simultaneously developed other approaches that participated in the same challenge. On two test sets, we demonstrate our segmentation performance and show that we achieve a tissue classification accuracy of 98% and 95%, making use of the inherent capability of our system to distinguish between benign and malignant tissue. Our results show that deep learning approaches can yield highly accurate and reproducible results for biomedical image analysis, with the potential to significantly improve the quality and speed of medical diagnoses. PMID:29018612

Vitamin K-Dependent Carboxylation of Matrix Gla Protein Influences the Risk of Calciphylaxis.

PubMed

Nigwekar, Sagar U; Bloch, Donald B; Nazarian, Rosalynn M; Vermeer, Cees; Booth, Sarah L; Xu, Dihua; Thadhani, Ravi I; Malhotra, Rajeev

2017-06-01

Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K-dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; P =0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses ( β =-8.99; P =0.04). In conclusion, vitamin K deficiency-mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study. Copyright © 2017 by the American Society of Nephrology.

Fabry disease presenting as apical left ventricular hypertrophy in a patient carrying the missense mutation R118C.

PubMed

Caetano, Francisca; Botelho, Ana; Mota, Paula; Silva, Joana; Leitão Marques, António

2014-03-01

Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by abnormalities of the GLA gene, which encodes the enzyme α-galactosidase A. A deficiency of this enzyme leads to the lysosomal accumulation of glycosphingolipids, which may cause left ventricular hypertrophy that is typically concentric and symmetric. We present the case of a 60-year-old woman with symptoms of dyspnea, atypical chest pain and palpitations, in whom a transthoracic echocardiogram revealed an apical variant of hypertrophic cardiomyopathy. Analysis of specific sarcomeric genetic mutations was negative. The patient underwent a screening protocol for Anderson-Fabry disease, using a dried blood spot test, which was standard at our institution for patients with left ventricular hypertrophy. The enzymatic activity assay revealed reduced α-galactosidase A enzymatic activity. Molecular analysis identified a missense point mutation in the GLA gene (p.R118C). This case report shows that Anderson-Fabry disease may cause an apical form of left ventricular hypertrophy. The diagnosis was only achieved because of systematic screening, which highlights the importance of screening for Anderson-Fabry disease in patients with unexplained left ventricular hypertrophy, including those presenting with more unusual patterns, such as apical variants of left ventricular hypertrophy. This case also supports the idea that the missense mutation R118C is indeed a true pathogenic mutation of Anderson-Fabry disease. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Potential effects of climate change on ground water in Lansing, Michigan

USGS Publications Warehouse

Croley, T.E.; Luukkonen, C.L.

2003-01-01

Computer simulations involving general circulation models, a hydrologic modeling system, and a ground water flow model indicate potential impacts of selected climate change projections on ground water levels in the Lansing, Michigan, area. General circulation models developed by the Canadian Climate Centre and the Hadley Centre generated meteorology estimates for 1961 through 1990 (as a reference condition) and for the 20 years centered on 2030 (as a changed climate condition). Using these meteorology estimates, the Great Lakes Environmental Research Laboratory's hydrologic modeling system produced corresponding period streamflow simulations. Ground water recharge was estimated from the streamflow simulations and from variables derived from the general circulation models. The U.S. Geological Survey developed a numerical ground water flow model of the Saginaw and glacial aquifers in the Tri-County region surrounding Lansing, Michigan. Model simulations, using the ground water recharge estimates, indicate changes in ground water levels. Within the Lansing area, simulated ground water levels in the Saginaw aquifer declined under the Canadian predictions and increased under the Hadley.

Technical Report Series on Global Modeling and Data Assimilation. Volume 16; Filtering Techniques on a Stretched Grid General Circulation Model

NASA Technical Reports Server (NTRS)

Takacs, Lawrence L.; Sawyer, William; Suarez, Max J. (Editor); Fox-Rabinowitz, Michael S.

1999-01-01

This report documents the techniques used to filter quantities on a stretched grid general circulation model. Standard high-latitude filtering techniques (e.g., using an FFT (Fast Fourier Transformations) to decompose and filter unstable harmonics at selected latitudes) applied on a stretched grid are shown to produce significant distortions of the prognostic state when used to control instabilities near the pole. A new filtering technique is developed which accurately accounts for the non-uniform grid by computing the eigenvectors and eigenfrequencies associated with the stretching. A filter function, constructed to selectively damp those modes whose associated eigenfrequencies exceed some critical value, is used to construct a set of grid-spaced weights which are shown to effectively filter without distortion. Both offline and GCM (General Circulation Model) experiments are shown using the new filtering technique. Finally, a brief examination is also made on the impact of applying the Shapiro filter on the stretched grid.

Integrated and spectral energetics of the GLAS general circulation model

NASA Technical Reports Server (NTRS)

Tenenbaum, J.

1982-01-01

Integrated and spectral error energetics of the GLAS General circulation model are compared with observations for periods in January 1975, 1976, and 1977. For two cases the model shows significant skill in predicting integrated energetics quantities out to two weeks, and for all three cases, the integrated monthly mean energetics show qualitative improvements over previous versions of the model in eddy kinetic energy and barotropic conversions. Fundamental difficulties remain with leakage of energy to the stratospheric level, particularly above strong initial jet streams associated in part with regions of steep terrain. The spectral error growth study represents the first comparison of general circulation model spectral energetics predictions with the corresponding observational spectra on a day by day basis. The major conclusion is that eddy kinetics energy can be correct while significant errors occur in the kinetic energy of wavenumber 3. Both the model and observations show evidence of single wavenumber dominance in eddy kinetic energy and the correlation of spectral kinetics and potential energy.

The 0.125 degree finite-volume General Circulation Model on the NASA Columbia Supercomputer: Preliminary Simulations of Mesoscale Vortices

NASA Technical Reports Server (NTRS)

Shen, B.-W.; Atlas, R.; Chern, J.-D.; Reale, O.; Lin, S.-J.; Lee, T.; Chang, J.

2005-01-01

The NASA Columbia supercomputer was ranked second on the TOP500 List in November, 2004. Such a quantum jump in computing power provides unprecedented opportunities to conduct ultra-high resolution simulations with the finite-volume General Circulation Model (fvGCM). During 2004, the model was run in realtime experimentally at 0.25 degree resolution producing remarkable hurricane forecasts [Atlas et al., 2005]. In 2005, the horizontal resolution was further doubled, which makes the fvGCM comparable to the first mesoscale resolving General Circulation Model at the Earth Simulator Center [Ohfuchi et al., 2004]. Nine 5-day 0.125 degree simulations of three hurricanes in 2004 are presented first for model validation. Then it is shown how the model can simulate the formation of the Catalina eddies and Hawaiian lee vortices, which are generated by the interaction of the synoptic-scale flow with surface forcing, and have never been reproduced in a GCM before.)

The Latest on the Venus Thermospheric General Circulation Model: Capabilities and Simulations

NASA Technical Reports Server (NTRS)

Brecht, A. S.; Bougher, S. W.; Parkinson, C. D.

2017-01-01

Venus has a complex and dynamic upper atmosphere. This has been observed many times by ground-based, orbiters, probes, and fly-by missions going to other planets. Two over-arching questions are generally asked when examining the Venus upper atmosphere: (1) what creates the complex structure in the atmosphere, and (2) what drives the varying dynamics. A great way to interpret and connect observations to address these questions utilizes numerical modeling; and in the case of the middle and upper atmosphere (above the cloud tops), a 3D hydrodynamic numerical model called the Venus Thermospheric General Circulation Model (VTGCM) can be used. The VTGCM can produce climatological averages of key features in comparison to observations (i.e. nightside temperature, O2 IR nightglow emission). More recently, the VTGCM has been expanded to include new chemical constituents and airglow emissions, as well as new parameterizations to address waves and their impact on the varying global circulation and corresponding airglow distributions.

A general circulation model study of the solar and QBO modulation of the stratospheric circulation during the northern hemisphere winter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodera, Kunihiko; Chiba, Masaru; Shibata, Kiyotaka

1991-07-01

A general circulation model has been used to study the modulation of north-polar temperatures during winter by both solar activity and the equatorial quasi-biennial oscillation (QBO). The variation of solar activity was simulated by changing the heating rate due to the absorption of ultraviolet (UV) radiation by ozone, while the QBO zonal wind fields were reproduced by incorporating zonal-momentum sources in the equatorial stratosphere. A total of 10 experiments were conducted by changing the heating rate from 70 to 110% for each of the simulated QBO easterly and westerly cases. The results of the numerical experiments show modulation effects similarmore » to those found by Labitzke (1987) in the 30-mb temperatures at the North Pole.« less

Using the Gamma-Poisson Model to Predict Library Circulations.

ERIC Educational Resources Information Center

Burrell, Quentin L.

1990-01-01

Argues that the gamma mixture of Poisson processes, for all its perceived defects, can be used to make predictions regarding future library book circulations of a quality adequate for general management requirements. The use of the model is extensively illustrated with data from two academic libraries. (Nine references) (CLB)

Stratospheric Ozone Distribution and Tropospheric General Circulation: Interconnections in the UTLS Region

NASA Astrophysics Data System (ADS)

Barodka, S.; Krasovsky, A.; Shalamyansky, A.

2014-12-01

The height of the tropopause, which divided the stratosphere and the troposphere, is a result of two rival categories of processes: the tropospheric vertical convection and the radiative heating of the stratosphere resulting from the ozone cycle. Hence, it is natural that tropospheric and stratospheric phenomena can have effect each other in manifold processes of stratosphere-troposphere interactions. In the present study we focus our attention to the "top-down" side of the interaction: the impact of stratospheric ozone distribution on the features of tropospheric circulation and the associated weather patterns and regional climate conditions. We proceed from analyzes of the observational data performed at the A.I. Voeikov Main Geophysical Observatory, which suggest a distinct correlation between stratospheric ozone distribution, synoptic formations and air-masses boundaries in the upper troposphere and the temperature field of the lower stratosphere [1]. Furthermore, we analyze local features of atmospheric general circulation and stratospheric ozone distribution from the atmospheric reanalyses and general circulation model data, focusing our attention to instantaneous positions of subtropical and polar stationary atmospheric fronts, which define regional characteristics of the general circulation cells in the troposphere and separate global tropospheric air-masses, correspond to distinct meteorological regimes in the TOC field [2, 3]. We assume that by altering the tropopause height, stratospheric ozone-related processes can have an impact on the location of the stationary atmospheric fronts, thereby exerting influence on circulation processes in troposphere and lower stratosphere. For midlatitudes, the tropopause height controls the position of the polar stationary front, which has a direct impact on the trajectory of motion of active vortices on synoptic tropospheric levels, thereby controlling weather patterns in that region and the regional climate. This mechanism is particularly important for the formation of blocking events. [1] A.M. Shalamyansky - Proceedings of Voeikov Main Geophysical Observatory, V. 568, pp. 173-194, 2013 (in Russian) [2] R.D. Hudson et al - J. Atmos. Sci., V. 60, pp. 1669-1677, 2003. [3] R.D. Hudson et al - Atmos. Chem. Phys., V. 6, pp. 5183-5191, 2006.

In-Situ Treatment of Groundwater Contaminated with Underground Coal Gasification Products / Oczyszczanie In-Situ WÓD Podziemnych Zanieczyszczonych Przez Produkty Podziemnego Zgazowania WĘGLA

NASA Astrophysics Data System (ADS)

Suponik, Tomasz; Lutyński, Marcin

2013-12-01

In the paper the contaminants that may be generated in Underground Coal Gasification (UCG) process were listed and include mainly mono- and polycyclic aromatic hydrocarbons, phenols, heavy metals, cyanides, ammonium, chloride and sulphate. As a method of UCG contaminated groundwater treatment a Permeable Reactive Barrier technology was proposed. To assess the effectiveness of this technology two tests were carried out. Granulated activated carbon (GAC) and zeolite, and granulated activated carbon and scrap iron were applied in the first and second test respectively. For these materials the hydro geological parameters called reactive material parameters were determined and discussed. The results of the experiments showed that GAC seems to be the most effective material for phenols, BTX, PAH, cyanides and slightly lowers ammonia removal, while zeolites and scrap iron removed free cyanide, ammonia and heavy metals respectively. Podziemne Zgazowanie Węgla (PZW) jest alternatywną metodą pozyskiwania energii z węgla. Jest to zespół przemian termicznych i chemicznych przebiegających bezpośrednio w złożu węgla, zachodzących pomiędzy substancją organiczną a czynnikiem zgazowującym, jakim może być powietrze, tlen, para wodna, dwutlenek węgla. Poza wieloma zaletami metoda ta niesie za sobą także wiele zagrożeń, które były rozważane w ramach projektu HUGE 2 (nr RFCR-CT-2011-00002). Jednym z nich jest zagrożenie środowiska wód podziemnych produktami PZW, do których należą wielopierścieniowe węglowodory aromatyczne, BTX, fenole, metale ciężkie, cyjanki, jony amonowe, chlorki i siarczany. W celu zminimalizowania tego zagrożenia w pracy rozważono zastosowanie w obszarze reaktora PZW technologii Przepuszczalnej Bariery Reaktywnej (PRB). W technologii tej zanieczyszczenia usuwane są in-situ poprzez przepływ wód przez odpowiednio dobrany materiał reaktywny. W tablicy 1 przedstawiono podstawowe parametry bariery, które należy określić, aby skutecznie i długotrwale chronić środowisko wodne przed zanieczyszczeniami. Jako materiał reaktywny w pracy wybrano, na podstawie zdolności oczyszczania, granulowany węgiel aktywny (do usuwania związków organicznych) oraz żelazo metaliczne i alternatywnie zeolity (do usuwaniazwiązków nieorganicznych i pozostałych związków organicznych po złożu węgla aktywnego). Badania prowadzone były w dwóch instalacjach badawczych składających się z pompy perystaltycznej oraz dwóch szeregowo połączonych szklanych kolumn filtracyjnych (rys. 1). W obu instalacjach pierwsza kolumna wypełniona była granulowanym węglem aktywnym, zaś druga odpowiednio w pierwszej i drugiej instalacji, żelazem metalicznym i zeolitami. Materiał reaktywny poza zdolnościami do usuwania zanieczyszczeń, musi również charakteryzować się długotrwałą i stabilną przepuszczalnością dla wód. Dlatego też jego skład ziarnowy dobrano w taki sposób, aby współczynnik filtracji materiału reaktywnego zawierał się między 2x10-4 i 6x10-3 m/s (co oznacza że powinien charakteryzować się maksymalnymi wartościami współczynnika filtracji dla piasku drobnoziarnistego i gruboziarnistego). Tabele 3 i 4 przedstawiają odpowiednio skład ziarnowy materiału reaktywnego zastosowanego w badaniach laboratoryjnych oraz jego główne parametry hydrogeologiczne. Zastosowany w badaniach roztwór przygotowany został poprzez zmieszanie wody destylowanej z odpowiednimi masami odczynników chemicznych, uzyskując w ten sposób stężenia zanieczyszczeń podobne do wartości przedstawionych w pracach (Kapusta & Stańczyk, 2011; Liu & in., 2006). W tabelach 5 i 6 oraz na rysunkach 2-8 przedstawiono wartości parametrów fizykochemicznych oraz stężeń substancji chemicznych zmierzonych w wodach pobranych z instalacji badawczych 1 i 2. We wnioskach pracy stwierdzono, iż granulowany węgiel aktywny jest odpowiednim materiałem do usuwania z wód fenoli, BTX, wielopierścieniowych węglowodorów aromatycznych, wolnych cyjanków oraz w mniejszym stopniu również jonów amonowych. Węgle nie wpływały na temperaturę wód oraz na potencjał redox i przewodność elektrolityczną. Zeolity z kolei skutecznie usuwały wolne cyjanki, jony amonowe oraz w pewnym stopniu fenole. W zależności od składu chemicznego wód oraz powinowactwa metali do zeolitów mogły one również usuwać metale ciężkie. Zeolity nie wpływały natomiast na temperaturę i powodowały znaczące obniżenie się wartości pH oraz przewodności elektrolitycznej wody. Przepływająca przez złoże zeolitu woda wzbogacała się z kolei (z całą pewnością w początkowym etapie pracy złoża) w rozpuszczony tlen, co miało odzwierciedlenie w wyższych wartościach potencjału redox w kolejnych punktach poboru wody. Ostatnim analizowanym w pracy materiałem było żelazo metaliczne. Chociaż nie wpływało ono w żaden sposób na stężenie związków organicznych w wodach, przyczyniło się do usunięcia z nich wszystkich metali ciężkich. Żelazo spowodowało ponadto wzrost temperatury i wartości pH oraz zdecydowane obniżenie się potencjału redox i stężenia tlenu rozpuszczonego. Rozważając zastosowanie wymienionych materiałów reaktywnych w technologii PRB do usuwania produktów PZW trzeba pamiętać o ograniczonej pojemności sorpcyjnej węgla aktywnego oraz zeolitów oraz o konieczności poddawania ich reaktywacji. Fakt ten oraz duże trudności technologiczne związane z zainstalowaniem materiału oraz jego wymianą stanowią wyzwanie do dalszych analiz i prac w tym obszarze.

Studies in the parameterization of cloudiness in climate models and the analysis of radiation fields in general circulation models

NASA Technical Reports Server (NTRS)

HARSHVARDHAN

1990-01-01

Broad-band parameterizations for atmospheric radiative transfer were developed for clear and cloudy skies. These were in the shortwave and longwave regions of the spectrum. These models were compared with other models in an international effort called ICRCCM (Intercomparison of Radiation Codes for Climate Models). The radiation package developed was used for simulations of a General Circulation Model (GCM). A synopsis is provided of the research accomplishments in the two areas separately. Details are available in the published literature.

Equatorial waves in the NCAR stratospheric general circulation model

NASA Technical Reports Server (NTRS)

Boville, B. A.

1985-01-01

Equatorially trapped wave modes are very important in the tropical stratospheric momentum balance. Kelvin waves and mixed Rossby-gravity waves are believed to be responsible for the quasi-biennial oscillation of the zonal winds in the equatorial lower stratosphere. Both Kelvin and mixed Rossby-gravity waves have been identified in observations and in numerical models. Kelvin and mixed Rossby-gravity waves are identified in a general circulation model extending from the surface into the mesosphere and looks at the effect on the waves of lowering the top of the model.

The significance of cloud-radiative forcing to the general circulation on climate time scales - A satellite interpretation

NASA Technical Reports Server (NTRS)

Sohn, Byung-Ju; Smith, Eric A.

1992-01-01

This paper focuses on the role of cloud- and surface-atmosphere forcing on the net radiation balance and their potential impact on the general circulation at climate time scales. The globally averaged cloud-forcing estimates and cloud sensitivity values taken from various recent studies are summarized. It is shown that the net radiative heating over the tropics is principally due to high clouds, while the net cooling in mid- and high latitudes is dominated by low and middle clouds.

Experience with a vectorized general circulation weather model on Star-100

NASA Technical Reports Server (NTRS)

Soll, D. B.; Habra, N. R.; Russell, G. L.

1977-01-01

A version of an atmospheric general circulation model was vectorized to run on a CDC STAR 100. The numerical model was coded and run in two different vector languages, CDC and LRLTRAN. A factor of 10 speed improvement over an IBM 360/95 was realized. Efficient use of the STAR machine required some redesigning of algorithms and logic. This precludes the application of vectorizing compilers on the original scalar code to achieve the same results. Vector languages permit a more natural and efficient formulation for such numerical codes.

High Strength Glass Second Source Qualification to Composite Armor Specification MIL-L-46197(MR)

DTIC Science & Technology

1992-04-01

L-46197 (MR). The Owens Corning Fiberglass (OCF) S-2 glass woven roving product has set the standard for this application to structural armor. The...HIARTMAN. 1). R. liallistc Penetration of S 2 Glass L~aminates S-2 Glass I-iber Technical Paper. Owens Corning Fiberglass. I I 1ASKLI.. W E. Spall...Materials Marketing. Owens Corning F’iberglass- Toledo. O1l, 416𔄃 SR and RI1 Gla" Chemical Composition. Vetrotex Data Sheet. IM11 04-02-2 6

Zonally averaged model of dynamics, chemistry and radiation for the atmosphere

NASA Technical Reports Server (NTRS)

Tung, K. K.

1985-01-01

A nongeostrophic theory of zonally averaged circulation is formulated using the nonlinear primitive equations on a sphere, taking advantage of the more direct relationship between the mean meridional circulation and diabatic heating rate which is available in isentropic coordinates. Possible differences between results of nongeostrophic theory and the commonly used geostrophic formulation are discussed concerning: (1) the role of eddy forcing of the diabatic circulation, and (2) the nonlinear nearly inviscid limit vs the geostrophic limit. Problems associated with the traditional Rossby number scaling in quasi-geostrophic formulations are pointed out and an alternate, more general scaling based on the smallness of mean meridional to zonal velocities for a rotating planet is suggested. Such a scaling recovers the geostrophic balanced wind relationship for the mean zonal flow but reveals that the mean meridional velocity is in general ageostrophic.

A Survey of Private Ohio Academic Libraries' Physical Processing Practices for Circulating Books.

ERIC Educational Resources Information Center

Factor, Olivia Spaid

Little guidance is given in today's general technical services or cataloging textbooks to assist librarians in making decisions on procedures for the physical preparation of materials prior to placement on the shelves for public access. As small, private academic libraries face automation of circulation, addition of security systems, and debates…

Cost-Effectiveness Analysis of the Automation of a Circulation System.

ERIC Educational Resources Information Center

Mosley, Isobel

A general methodology for cost effectiveness analysis was developed and applied to the Colorado State University library loan desk. The cost effectiveness of the existing semi-automated circulation system was compared with that of a fully manual one, based on the existing manual subsystem. Faculty users' time and computer operating costs were…

Neural Control of the Circulation

ERIC Educational Resources Information Center

Thomas, Gail D.

2011-01-01

The purpose of this brief review is to highlight key concepts about the neural control of the circulation that graduate and medical students should be expected to incorporate into their general knowledge of human physiology. The focus is largely on the sympathetic nerves, which have a dominant role in cardiovascular control due to their effects to…

An Improved Heat Budget Estimation Including Bottom Effects for General Ocean Circulation Models

NASA Technical Reports Server (NTRS)

Carder, Kendall; Warrior, Hari; Otis, Daniel; Chen, R. F.

2001-01-01

This paper studies the effects of the underwater light field on heat-budget calculations of general ocean circulation models for shallow waters. The presence of a bottom significantly alters the estimated heat budget in shallow waters, which affects the corresponding thermal stratification and hence modifies the circulation. Based on the data collected during the COBOP field experiment near the Bahamas, we have used a one-dimensional turbulence closure model to show the influence of the bottom reflection and absorption on the sea surface temperature field. The water depth has an almost one-to-one correlation with the temperature rise. Effects of varying the bottom albedo by replacing the sea grass bed with a coral sand bottom, also has an appreciable effect on the heat budget of the shallow regions. We believe that the differences in the heat budget for the shallow areas will have an influence on the local circulation processes and especially on the evaporative and long-wave heat losses for these areas. The ultimate effects on humidity and cloudiness of the region are expected to be significant as well.

Does familiarity or conflict account for performance in the word-stem completion task? Evidence from behavioural and event-related-potential data.

PubMed

Klonek, Florian; Tamm, Sascha; Hofmann, Markus J; Jacobs, Arthur M

2009-11-01

The conflict monitoring theory (CMT) assumes that word-stems associated with several completions should lead to crosstalk and conflict due to underdetermined responding situation (Botvinick et al. in Psychol Rev 108(3):624-652, 2001). In contrast, the Multiple-Read-Out-Model (MROM) of Jacobs and Grainger (J Exp Psychol 20(6): 1311-1334, 1994) predicts a high level of general lexical activity (GLA) for word-stems with many completions, indicating a higher stimulus familiarity because these stems are more probable to be read. We compared word-stems with several completions against word-stems with one possible completion while measuring response times and electrophysiological recordings. Slowest response times and a distinct FN400 component, which has previously been related to the concept of familiarity (Curran in Memory Cogn 28(6):923-938, 2000), were apparent for word-stems that could only be associated with a single response. These findings support the claims of the MROM. Furthermore, the lack of the N2-component for word-stems with several completions continues to challenge the EEG-extension of the CMT (Yeung et al. in Psychol Rev 111(4):2004).

An analysis of the synoptic and climatological applicability of circulation type classifications for Ireland

NASA Astrophysics Data System (ADS)

Broderick, Ciaran; Fealy, Rowan

2013-04-01

Circulation type classifications (CTCs) compiled as part of the COST733 Action, entitled 'Harmonisation and Application of Weather Type Classifications for European Regions', are examined for their synoptic and climatological applicability to Ireland based on their ability to characterise surface temperature and precipitation. In all 16 different objective classification schemes, representative of four different methodological approaches to circulation typing (optimization algorithms, threshold based methods, eigenvector techniques and leader algorithms) are considered. Several statistical metrics which variously quantify the ability of CTCs to discretize daily data into well-defined homogeneous groups are used to evaluate and compare different approaches to synoptic typing. The records from 14 meteorological stations located across the island of Ireland are used in the study. The results indicate that while it was not possible to identify a single optimum classification or approach to circulation typing - conditional on the location and surface variables considered - a number of general assertions regarding the performance of different schemes can be made. The findings for surface temperature indicate that that those classifications based on predefined thresholds (e.g. Litynski, GrossWetterTypes and original Lamb Weather Type) perform well, as do the Kruizinga and Lund classification schemes. Similarly for precipitation predefined type classifications return high skill scores, as do those classifications derived using some optimization procedure (e.g. SANDRA, Self Organizing Maps and K-Means clustering). For both temperature and precipitation the results generally indicate that the classifications perform best for the winter season - reflecting the closer coupling between large-scale circulation and surface conditions during this period. In contrast to the findings for temperature, spatial patterns in the performance of classifications were more evident for precipitation. In the case of this variable those more westerly synoptic stations open to zonal airflow and less influenced by regional scale forcings generally exhibited a stronger link with large-scale circulation.

General Circulation Model Simulations of the Annual Cycle of Martian Climate

NASA Astrophysics Data System (ADS)

Wilson, R.; Richardson, M.; Rodin, A.

Observations of the martian atmosphere have revealed a strong annual modulation of global mean atmospheric temperature that has been attributed to the pronounced seasonal asymmetry in solar radiation and the highly variable distribution of aerosol. These observations indicate little interannual variability during the relatively cool aphelion season and considerable variability in the perihelion season that is associated with the episodic occurrence of regional and major dust storms. The atmospheric circulation responds to the evolving spatial distribution of aerosol-induced heating and, in turn, plays a major role in determining the sources, sinks, and transport of radiatively active aerosol. We will present simulations employing the GFDL Mars General Circulation Model (MGCM) that show that aspects of the seasonally evolving climate may be simulated in a self-consistent manner using simple dust source parameterizations that represent the effects of lifting associated with local dust storms, dust devil activity, and other processes. Aerosol transport is accomplished, in large part, by elements of the large-scale circulation such as the Hadley circulation, baroclinic storms, tides, etc. A seasonal cycle of atmospheric opacity and temperature results from the variation in the strength and distribution of dust sources as well as from seasonal variations in the efficiency of atmospheric transport associated with changes in the circulation between solstice and equinox, and between perihelion and aphelion. We examine the efficiency of atmospheric transport of dust lifted along the perimeter of the polar caps to gauge the influence of these storms on the global circulation. We also consider the influence of water, as the formation of water ice clouds on dust nuclei may also affect the vertical distribution of dust and strongly influence the aerosol radiative properties.

Numerical modeling of general circulation, thermohaline structure, and residence time in Gorgan Bay, Iran

NASA Astrophysics Data System (ADS)

Ranjbar, Mohammad Hassan; Hadjizadeh Zaker, Nasser

2018-01-01

Gorgan Bay is a semi-enclosed basin located in the southeast of the Caspian Sea, Iran. The bay is recognized as a resting place for migratory birds as well as a spawning habitat for native fish. However, apparently, no detailed research on its physical processes has previously been conducted. In this study, a 3D coupled hydrodynamic and solute transport model was used to investigate general circulation, thermohaline structure, and residence time in Gorgan Bay. Model outputs were validated against a set of field observations. Bottom friction and attenuation coefficient of light intensity were tuned in order to achieve optimum agreement with the observations. Results revealed that, due to the interaction between bathymetry and prevailing winds, a barotropic double-gyre circulation, dominating the general circulation, existed during all seasons in Gorgan Bay. Furthermore, temperature and salinity fluctuations in the bay were seasonal, due to the seasonal variability of atmospheric fluxes. Results also indicated that under the prevailing winds, the domain-averaged residence time in Gorgan Bay would be approximately 95 days. The rivers discharging into Gorgan Bay are considered as the main sources of nutrients in the bay. Since their mouths are located in the area with a residence time of over 100 days, Gorgan Bay could be at risk of eutrophication; it is necessary to adopt preventive measures against water quality degradation.

Properties of Waste from Coal Gasification in Entrained Flow Reactors in the Aspect of Their Use in Mining Technology / Właściwości odpadów ze zgazowania węgla w reaktorach dyspersyjnych w aspekcie ich wykorzystania w technologiach górniczych

NASA Astrophysics Data System (ADS)

Pomykała, Radosław

2013-06-01

Most of the coal gasification plants based of one of the three main types of reactors: fixed bed, fluidized bed or entrained flow. In recent years, the last ones, which works as "slagging" reactors (due to the form of generated waste), are very popular among commercial installations. The article discusses the characteristics of the waste from coal gasification in entrained flow reactors, obtained from three foreign installations. The studies was conducted in terms of the possibilities of use these wastes in mining technologies, characteristic for Polish underground coal mines. The results were compared with the requirements of Polish Standards for the materials used in hydraulic backfill as well as suspension technology: solidification backfill and mixtures for gob caulking. Większość przemysłowych instalacji zgazowania węgla pracuje w oparciu o jeden z trzech głównych typów reaktorów: ze złożem stałym, dyspersyjny lub fluidalny. W zależności od rodzaju reaktora oraz szczegółowych rozwiązań instalacji, powstające uboczne produkty zgazowania mogą mieć różną postać. Zależy ona w dużej mierze od stosunku temperatury pracy reaktora do temperatury topnienia części mineralnych zawartych w paliwie, czyli do temperatury mięknienia i topnienia popiołu. W ostatnich latach bardzo dużą popularność wśród instalacji komercyjnych zdobywają reaktory dyspersyjne "żużlujące". W takich instalacjach żużel jest wychwytywany i studzony po wypłynięciu z reaktora. W niektórych przypadkach oprócz żużla powstaje jeszcze popiół lotny, wychwytywany w systemach odprowadzania spalin. Może być on pozyskiwany oddzielnie lub też zawracany do komory reaktora, gdzie ulega stopieniu. Wszystkie z analizowanych odpadów - trzy żużle oraz popiół pochodzą właśnie z tego typu instalacji. Tylko z jednej z nich pozyskano zarówno żużel jak i popiół, z pozostałych dwóch jedynie żużel. Odpady te powstały, jako uboczny produkt zgazowania węgla lub węgla z dodatkami: bitumin (żużel S1), czy biomasy (popiół A2, żużel S2). W polskim górnictwie podziemnym wyróżnić można kilka technologii podsadzkowych, w których do transportu materiału wykorzystywana jest woda. Tradycyjnie oraz ze względów historycznych, terminem "podsadzka hydrauliczna" określa się tę, która spełnia wymagania normy PN-93/G-11010. Do najważniejszych cech takiej podsadzki hydraulicznej zaliczyć należy wypełnienia uprzednio wydzielonej pustki poeksploatacyjnej, materiałem o jak najmniejszej ściśliwości oraz o jak największej wodoprzepuszczalności. Materiał taki, po odprowadzeniu wody ma stanowić mechaniczna podporę stropu, a proces podsadzania jest ściśle powiązany z procesem eksploatacji, jako sposób likwidacji zrobów. Najczęściej stosowanymi materiałami są piasek podsadzkowy oraz odpady górnicze lub hutnicze (Lisowski, 1997). Od ponad dwudziestu lat, w polskim górnictwie węgla kamiennego obecna jest również inna technologia podsadzkowa, w której do transportu materiałów wykorzystywana jest woda. W tym przypadku części stałe to materiały drobnoziarniste, najczęściej popioły różnych typów, które po wymieszaniu z wodą tworzą zawiesinę (stąd termin "zawiesiny popiołowo-wodne"). Polska norma PN-G-11011:1998 wyróżnia dwie odmiany takich zawiesin i definiuje je, jako "podsadzkę zestalaną" oraz "mieszaninę do doszczelniania zrobów". Podstawową ideą przyświecającą stosowaniu zawiesin drobnoziarnistych w technologiach górniczych była początkowo troska o zagospodarowaniu odpadów energetycznych, a następnie górniczych (Mazurkiewicz i in., 1998; Piotrowski i in., 2006; Piotrowski, 2010; Plewa i Mysłek, 2000; Plewa i Sobota, 2002). Obecnie technologia zawiesinowa na stałe zagościła w kopalniach węgla kamiennego stając się m.in. nieodzownym środkiem profilaktyki pożarowej i metanowej (Dziurzyński i Pomykała, 2006; Palarski, 2004; Pomykała, 2006). W artykule przedstawiono analizę możliwości wykorzystania ubocznych produktów zgazowania, jako materiałów do podsadzki hydrauliczne (wg normy PN-93/G-11010), podsadzki zestalanej oraz mieszaniny do doszczelniania zrobów (wg normy PN-G-11011:1998) - technologii stosowanych w polskim górnictwie węgla kamiennego. Podstawowe badania ubocznych produktów zgazowania obejmowały takie właściwości jak gęstość, wilgotność, skład ziarnowy, wymywalność zanieczyszczeń chemicznych oraz zawartość radionuklidów. Wybrane właściwości fizyczne ubocznych produktów zgazowania oraz ich oznaczenie zestawiono w tabeli 1. Składy ziarnowe żużli ze zgazowania, analizowanych pod kątem zastosowania w podsadzce hydraulicznej przedstawiono na rys. 1, a materiałów dla technologii zawiesinowej, czyli popiołu lotnego A2 oraz zmielonych żużli oznaczonych, jako S1m, S2m oraz S3m - na rys. 2. Żużle ze zgazowania zawierają nie więcej niż 6% ziaren mniejszych niż 0,1 mm, co odpowiada wymaganiom dla materiałów podsadzkowych I klasy. Analiza wymywalności zanieczyszczeń chemicznych wykazała przekroczenia wymagań jednej lub obu przywołanych norm w zakresie pH i/lub niklu dla próbek żużli S1 i S2 oraz popiołu A2 (tab. 2). Zwraca uwagę bardzo niska wartość pH oraz bardzo wysoka zawartość niklu dla żużla S1. Jest to rzecz nietypowa dla krajowych odpadów energetycznych powstających ze spalania węgla kamiennego. W zakresie zawartości radionuklidów wszystkie materiały spełniają nie tylko wymagania norm podsadzkowych, ale również wymagania stawiane materiałom budowlanym (tab. 3). Ściśliwość żużli ze zgazowania kształtuje się na poziomie 11÷14%, co pozwala zakwalifikować je do materiałów podsadzkowych III klasy. Aby uzyskać materiał wyższej klasy, konieczne jest zmieszanie żużli z piaskiem podsadzkowych. W zakresie wodoprzepuszczalności wszystkie żużle kwalifikują się, jako materiał podsadzkowy klasy I (rys. 5, tab. 4). W normie PN-G-11011:1998 określone zostały wymagania podsadzki zestalanej oraz dla mieszaniny do doszczelniania zrobów. (tab. 5), tylko dla części badań wskazane są konkretne wymagania ilościowe. Wyniki badań wymywalność zanieczyszczeń chemicznych oraz zawartości radionuklidów zostały omówione wcześniej. Właściwości zawiesin w stanie płynnym zestawiono w tabeli 6. oraz na rys. 7, 8 i 9., a parametry reologiczne wg modelu Binghama na rys. 10÷13. Wymagania w zakresie właściwości zestalonych zawiesin tj. wytrzymałości na jednoosiowe ściskanie oraz rozmakalności zostały ściśle określone dla podsadzki zestalanej jak i mieszaniny do doszczelniania zrobów (tab. 5). Zawiesiny przygotowane na bazie odpadów ze zgazowania węgla nie wykazują właściwości wiążących. Zarówno ze względu na wytrzymałość na jednoosiowe ściskanie (rys. 14) jak i rozmakalność (rys. 15) kwalifikują się jedynie, jako mieszaniny do doszczelniania zrobów. Przeprowadzone badania wstępnie potwierdziły możliwość zastosowania ubocznych produktów zgazowania pochodzących z instalacji bazujących na reaktorach dyspersyjnych, w technologiach górniczych charakterystycznych dla polskiego górnictwa podziemnego. Dla ostatecznego potwierdzenia konieczne są oczywiście badania dokładnie tych odpadów, które miałyby być stosowane w konkretnych kopalniach. Przyszłe wykorzystanie zastosowania odpadów z procesu zgazowania węgla, jako materiałów podsadzkowych zależy od wielu czynników, do których zaliczyć należą: dalszy rozwój technologii podsadzki hydraulicznej w górnictwie polskim, a także właściwości i dostępność tego typu materiałów powstałych ze zgazowania polskich węgli i/oraz w instalacjach na terenie Polski.

Seasonal Overturning Circulation in the Red Sea

NASA Astrophysics Data System (ADS)

Yao, F.; Hoteit, I.; Koehl, A.

2010-12-01

The Red Sea exhibits a distinct seasonal overturning circulation. In winter, a typical two-layer exchange structure, with a fresher inflow from the Gulf of Aden on top of an outflow from the Red Sea, is established. In summer months (June to September) this circulation pattern is changed to a three-layer structure: a surface outflow from the Red Sea on top of a subsurface intrusion of the Gulf of Aden Intermediate Water and a weakened deep outflow. This seasonal variability is studied using a general circulation model, MITgcm, with 6 hourly NCEP atmospheric forcing. The model is able to reproduce the observed seasonal variability very well. The forcing mechanisms of the seasonal variability related to seasonal surface wind stress and buoyancy flux, and water mass transformation processes associated with the seasonal overturning circulation are analyzed and presented.

Decision Support Tool Evaluation Report for General NOAA Oil Modeling Environment(GNOME) Version 2.0

NASA Technical Reports Server (NTRS)

Spruce, Joseph P.; Hall, Callie; Zanoni, Vicki; Blonski, Slawomir; D'Sa, Eurico; Estep, Lee; Holland, Donald; Moore, Roxzana F.; Pagnutti, Mary; Terrie, Gregory

2004-01-01

NASA's Earth Science Applications Directorate evaluated the potential of NASA remote sensing data and modeling products to enhance the General NOAA Oil Modeling Environment (GNOME) decision support tool. NOAA's Office of Response and Restoration (OR&R) Hazardous Materials (HAZMAT) Response Division is interested in enhancing GNOME with near-realtime (NRT) NASA remote sensing products on oceanic winds and ocean circulation. The NASA SeaWinds sea surface wind and Jason-1 sea surface height NRT products have potential, as do sea surface temperature and reflectance products from the Moderate Resolution Imaging Spectroradiometer and sea surface reflectance products from Landsat and the Advanced Spaceborne Thermal Emission and Reflectance Radiometer. HAZMAT is also interested in the Advanced Circulation model and the Ocean General Circulation Model. Certain issues must be considered, including lack of data continuity, marginal data redundancy, and data formatting problems. Spatial resolution is an issue for near-shore GNOME applications. Additional work will be needed to incorporate NASA inputs into GNOME, including verification and validation of data products, algorithms, models, and NRT data.

Tidal flushing and wind driven circulation of Ahe atoll lagoon (Tuamotu Archipelago, French Polynesia) from in situ observations and numerical modelling.

PubMed

Dumas, F; Le Gendre, R; Thomas, Y; Andréfouët, S

2012-01-01

Hydrodynamic functioning and water circulation of the semi-closed deep lagoon of Ahe atoll (Tuamotu Archipelago, French Polynesia) were investigated using 1 year of field data and a 3D hydrodynamical model. Tidal amplitude averaged less than 30 cm, but tide generated very strong currents (2 ms(-1)) in the pass, creating a jet-like circulation that partitioned the lagoon into three residual circulation cells. The pass entirely flushed excess water brought by waves-induced radiation stress. Circulation patterns were computed for climatological meteorological conditions and summarized with stream function and flushing time. Lagoon hydrodynamics and general overturning circulation was driven by wind. Renewal time was 250 days, whereas the e-flushing time yielded a lagoon-wide 80-days average. Tide-driven flush through the pass and wind-driven overturning circulation designate Ahe as a wind-driven, tidally and weakly wave-flushed deep lagoon. The 3D model allows studying pearl oyster larvae dispersal in both realistic and climatological conditions for aquaculture applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

PUFA-induced cell death is mediated by Yca1p-dependent and -independent pathways, and is reduced by vitamin C in yeast.

PubMed

Johansson, Magnus; Chen, Xin; Milanova, Stefina; Santos, Cristiano; Petranovic, Dina

2016-03-01

Polyunsaturated fatty acids (PUFA) such as linoleic acid (LA, n-6, C18:2) and γ-linolenic acid (GLA, n-6, C18:3) are essential and must be obtained from the diet. There has been a growing interest in establishing a bio-sustainable production of PUFA in several microorganisms, e.g. in yeast Saccharomyces cerevisiae. However, PUFAs can also be toxic to cells because of their susceptibility to peroxidation. Here we investigated the negative effects of LA and GLA production on S. cerevisiae by characterizing a strain expressing active Δ6 and Δ12 desaturases from the fungus Mucor rouxii. Previously, we showed that the PUFA-producing strain has low viability, down-regulated genes for oxidative stress response, and decreased proteasome activity. Here we show that the PUFA strain accumulates high levels of reactive oxygen species (ROS) and lipid peroxides, and accumulates damaged proteins. The PUFA strain also showed great increase in metacaspase Yca1p activity, suggesting cells could die by caspase-mediated cell death. When treated with antioxidant vitamin C, ROS, lipid peroxidation and protein carbonylation were greatly reduced, and the activity of the metacaspase was significantly decreased too, ultimately doubling the lifespan of the PUFA strain. When deleting YCA1, the caspase-like activity and the oxidative stress decreased and although the lifespan was slightly prolonged, the phenotype could not be fully reversed, pointing that Yca1p was not the main executor of cell death. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Decreased expression of γ-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein.

PubMed

Doyon, Marielle; Mathieu, Patrick; Moreau, Pierre

2013-02-01

Arterial stiffness is accelerated in type 1 diabetic patients. Medial artery calcification (MAC) contributes to the development of arterial stiffness. Vitamin K oxidoreductase (VKOR) reduces the vitamin K required by γ-carboxylase to activate matrix γ-carboxyglutamic acid (Gla) protein (MGP), an inhibitor of vascular calcification. This study aimed to evaluate the hypothesis that diabetes reduces the γ-carboxylation of MGP in the aortic wall, leading to increased vascular calcification, and the role of γ-carboxylase and VKOR in this γ-carboxylation deficit. Type 1 diabetes was induced in male Wistar rats with a single ip injection of streptozotocin. Augmentation of arterial stiffness in diabetic rats was shown by a 44% increase in aortic pulse wave velocity. Aortic and femoral calcification were increased by 26 and 56%, respectively. γ-Carboxylated MGP (cMGP, active) was reduced by 36% and the aortic expression of γ-carboxylase was reduced by 58%. Expression of γ-carboxylase correlated with cMGP (r= 0.59) and aortic calcification (r = -0.57). VKOR aortic expression and activity were not modified by diabetes. Vitamin K plasma concentrations were increased by 191% in diabetic rats. In ex vivo experiments with aortic rings, vitamin K supplementation prevented the glucose-induced decrease in γ-carboxylase expression. Our results suggest that reduced cMGP, through an impaired expression of γ-carboxylase, is involved in the early development of MAC in diabetes, and therefore, in the acceleration of arterial stiffness. A defect in vitamin K uptake by target cells could also be involved.

Variation in the fatty-acid content in seeds of various black, red, and white currant varieties.

PubMed

Šavikin, Katarina P; Ðorđević, Boban S; Ristić, Mihailo S; Krivokuća-Ðokić, Dragana; Pljevljakušić, Dejan S; Vulić, Todor

2013-01-01

Currant seeds, a by-product of juice production, are recognized as a valuable source of oil rich in polyunsaturated fatty acids. We have evaluated 28 currant varieties for their oil content and fatty-acid composition. The oil content in the seeds ranged from 18.2-27.7%, and no statistical difference between varieties of different fruit color were recorded. Furthermore, the estimated oil yields in the field production ranged from 26.4-212.4 kg/ha. The GC and GC/MS chemical profiles of the seed oils extracted from all examined varieties were common for currants. Linoleic acid (LA) was the major component, with contents ranging from 32.7-46.9% of total fatty acids, followed by α-linolenic acid (ALA; 2.9-32.0 %), oleic acid (OA; 9.8-19.9%), γ-linolenic acid (GLA; 3.3-18.5%), palmitic acid (PA; 4.4-8.1%), stearidonic acid (SDA; 2.2-4.7%), and stearic acid (SA; 1.2-2.4%). Quantitative differences in the fatty-acid profiles between varieties of different fruit color were observed. Blackcurrant varieties showed significantly higher contents of LA, GLA, and PA than red and white currant varieties, whereas significantly higher amounts of ALA and OL were detected in the red and white varieties. Cluster analysis based on the chemical oil profiles joined the blackcurrants in one group, while most of the red and white cultivars joined in a second group at the same linkage distance. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

PubMed

San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

2014-06-06

Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey.

PubMed

Huzmeli, Can; Candan, Ferhan; Alaygut, Demet; Bagci, Gokhan; Akkaya, Lale; Bagci, Binnur; Sozmen, Eser Yıldırım; Kurtulgan, Hande Kucuk; Kayatas, Mansur

2016-08-01

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.

Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study.

PubMed

Germain, Dominique P; Brand, Eva; Burlina, Alessandro; Cecchi, Franco; Garman, Scott C; Kempf, Judy; Laney, Dawn A; Linhart, Aleš; Maródi, László; Nicholls, Kathy; Ortiz, Alberto; Pieruzzi, Federico; Shankar, Suma P; Waldek, Stephen; Wanner, Christoph; Jovanovic, Ana

2018-04-12

The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease. To expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events. In p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3%). p.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

The influence of phosphate, calcium and magnesium on matrix Gla-protein and vascular calcification: a systematic review.

PubMed

Houben, E; Neradova, A; Schurgers, L J; Vervloet, Marc

2016-01-01

Vitamin K-dependent matrix Gla protein (MGP) is a key inhibitor of vascular calcification (VC). MGP is synthesized by chondrocytes and vascular smooth muscle cells (VSMC) and the absence or inactivity of MGP results in excessive calcification of both growth plate and vasculature. Apart from its vitamin K dependency little is known about other factors that influence MGP metabolism. Phosphate, calcium and magnesium are involved in bone mineralization and play an important role in VC. In this review we provide a summary of the effect of phosphate, calcium, and magnesium on MGP metabolism. Elevated phosphate and calcium levels promote VC, in part by increasing the release of matrix vesicles (MV) that under the influence of calcium and phosphate become calcification competent. Phosphate and calcium simultaneously induce an upregulation of MGP protein and gene expression, which possibly inhibits calcification. Elevated phosphate levels did not change MGP protein levels in MV. On the contrary, elevated calcium concentrations caused a decrease of MGPloading in MV, which might in part explainthe calcifying effects of MV. Magnesium is a known inhibitor of VC. However, magnesium has been shown to have an inhibitory effect on MGP synthesis induced through downregulation of the calcium-sensing receptor and hereby causing a decrease in calcium induced MGP upregulation. There might also be stimulatory effect of magnesium on MGP in which the TRPM7 channel is involved. In conclusion there is a clear interaction between MGP and phosphate, calcium and magnesium. The upregulation of MGP by phosphate and calcium might be a cellular response that possibly results in the mitigation of VC.

Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study.

PubMed

Morinaga, Jun; Zhao, Jiabin; Endo, Motoyoshi; Kadomatsu, Tsuyoshi; Miyata, Keishi; Sugizaki, Taichi; Okadome, Yusuke; Tian, Zhe; Horiguchi, Haruki; Miyashita, Kazuya; Maruyama, Nobuhiro; Mukoyama, Masashi; Oike, Yuichi

2018-01-01

Angiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors. We conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation. Circulating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels. Circulating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development.

A simple biosphere model (SiB) for use within general circulation models

NASA Technical Reports Server (NTRS)

Sellers, P. J.; Mintz, Y.; Sud, Y. C.; Dalcher, A.

1986-01-01

A simple realistic biosphere model for calculating the transfer of energy, mass and momentum between the atmosphere and the vegetated surface of the earth has been developed for use in atmospheric general circulation models. The vegetation in each terrestrial model grid is represented by an upper level, representing the perennial canopy of trees and shrubs, and a lower level, representing the annual cover of grasses and other heraceous species. The vegetation morphology and the physical and physiological properties of the vegetation layers determine such properties as: the reflection, transmission, absorption and emission of direct and diffuse radiation; the infiltration, drainage, and storage of the residual rainfall in the soil; and the control over the stomatal functioning. The model, with prescribed vegetation parameters and soil interactive soil moisture, can be used for prediction of the atmospheric circulation and precipitaion fields for short periods of up to a few weeks.

Improved short-term variability in the thermosphere-ionosphere-mesosphere-electrodynamics general circulation model

NASA Astrophysics Data System (ADS)

Häusler, K.; Hagan, M. E.; Baumgaertner, A. J. G.; Maute, A.; Lu, G.; Doornbos, E.; Bruinsma, S.; Forbes, J. M.; Gasperini, F.

2014-08-01

We report on a new source of tidal variability in the National Center for Atmospheric Research thermosphere-ionosphere-mesosphere-electrodynamics general circulation model (TIME-GCM). Lower boundary forcing of the TIME-GCM for a simulation of November-December 2009 based on 3-hourly Modern-Era Retrospective Analysis for Research and Application (MERRA) reanalysis data includes day-to-day variations in both diurnal and semidiurnal tides of tropospheric origin. Comparison with TIME-GCM results from a heretofore standard simulation that includes climatological tropospheric tides from the global-scale wave model reveal evidence of the impacts of MERRA forcing throughout the model domain, including measurable tidal variability in the TIME-GCM upper thermosphere. Additional comparisons with measurements made by the Gravity field and steady-state Ocean Circulation Explorer satellite show improved TIME-GCM capability to capture day-to-day variations in thermospheric density for the November-December 2009 period with the new MERRA lower boundary forcing.

Traditional Aids to Navigation: The Next 25 Years

NASA Astrophysics Data System (ADS)

Turner, Neil Macdonald

The authors of this paper are the three General Lighthouse Authorities (GLAs) of the United Kingdom and the Republic of Ireland. It was presented on their behalf at the RIN-96 conference by Captain Turner. The paper gives a brief overview of the policy of the GLAs (i.e. the Corporation of Trinity House, the Northern Lighthouse Board and the Commissioners of Irish Lights) regarding the provision of an aids to navigation service with emphasis on the future prospects of traditional aids to navigation over the next 25 years. The three GLAs have recently carried out a consultation exercise on marine aids to navigation into the 21st century. The results of this consultation exercise are discussed. It should be noted that, for clarity, the General Lighthouse Authorities (GLAs) refer to the systems that they provide as (AtoN), to differentiate their provision from the equipment carried on board ships for navigational purposes which are referred to by the GLAs as . This paper therefore in the main deals with AtoN.The coastlines within the GLAs' areas of responsibility rank with the most heavily trafficked and dangerous in the world. The coastlines vary from isolated rocks and the steep, Atlantic coastline, to the low-lying relatively featureless coastline of south-east England, off which are shifting sandbanks and channels. The tidal range in GLA waters is significant and tidal streams can reach 10 knots or more in a number of places.

A Pharmacogenetic Approach to Identify Mutant Forms of α-Galactosidase A that Respond to a Pharmacological Chaperone for Fabry Disease

PubMed Central

Wu, Xiaoyang; Katz, Evan; Valle, Maria Cecilia Della; Mascioli, Kirsten; Flanagan, John J; Castelli, Jeffrey P; Schiffmann, Raphael; Boudes, Pol; Lockhart, David J; Valenzano, Kenneth J; Benjamin, Elfrida R

2011-01-01

Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mutant forms (defined as “responsive”). In this study, we developed a cell-based assay in cultured HEK-293 cells to identify mutant forms of α-Gal A that are responsive to AT1001. Concentration-dependent increases in α-Gal A activity in response to AT1001 were shown for 49 (60%) of 81 mutant forms. The responses of α-Gal A mutant forms were generally consistent with the responses observed in male Fabry patient-derived lymphoblasts. Importantly, the HEK-293 cell responses of 19 α-Gal A mutant forms to a clinically achievable concentration of AT1001 (10 µM) were generally consistent with observed increases in α-Gal A activity in peripheral blood mononuclear cells from male Fabry patients orally administered AT1001 during Phase 2 clinical studies. This indicates that the cell-based responses can identify mutant forms of α-Gal A that are likely to respond to AT1001 in vivo. Thus, the HEK-293 cell-based assay may be a useful aid in the identification of Fabry patients with AT1001-responsive mutant forms. Hum Mutat 32:1–13, 2011. © 2011 Wiley-Liss, Inc. PMID:21598360

Pacific deep circulation and ventilation controlled by tidal mixing away from the sea bottom.

PubMed

Oka, Akira; Niwa, Yoshihiro

2013-01-01

Vertical mixing in the ocean is a key driver of the global ocean thermohaline circulation, one of the most important factors controlling past and future climate change. Prior observational and theoretical studies have focused on intense tidal mixing near the sea bottom (near-field mixing). However, ocean general circulation models that employ a parameterization of near-field mixing significantly underestimate the strength of the Pacific thermohaline circulation. Here we demonstrate that tidally induced mixing away from the sea bottom (far-field mixing) is essential in controlling the Pacific thermohaline circulation. Via the addition of far-field mixing to a widely used tidal parameterization, we successfully simulate the Pacific thermohaline circulation. We also propose that far-field mixing is indispensable for explaining the presence of the world ocean's oldest water in the eastern North Pacific Ocean. Our findings suggest that far-field mixing controls ventilation of the deep Pacific Ocean, a process important for ocean carbon and biogeochemical cycles.

Multiple states in the late Eocene ocean circulation

NASA Astrophysics Data System (ADS)

Baatsen, M. L. J.; von der Heydt, A. S.; Kliphuis, M.; Viebahn, J.; Dijkstra, H. A.

2018-04-01

The Eocene-Oligocene Transition (EOT) marks a major step within the Cenozoic climate in going from a greenhouse into an icehouse state, with the formation of a continental-scale Antarctic ice sheet. The roles of steadily decreasing CO2 concentrations versus changes in ocean circulation at the EOT are still debated and the threshold for Antarctic glaciation is obscured by uncertainties in global geometry. Here, a detailed study of the late Eocene ocean circulation is carried out using an ocean general circulation model under two slightly different geography reconstructions of the middle-to-late Eocene (38 Ma). Using the same atmospheric forcing, both geographies give a profoundly different equilibrium ocean circulation state. The underlying reason for this sensitivity is the presence of multiple equilibria characterised by either North or South Pacific deep water formation. A possible shift from a southern towards a northern overturning circulation would result in significant changes in the global heat distribution and consequently make the Southern Hemisphere climate more susceptible for significant cooling and ice sheet formation on Antarctica.

Magnetic Flux Circulation During Dawn-Dusk Oriented Interplanetary Magnetic Field

NASA Technical Reports Server (NTRS)

Mitchell, E. J.; Lopez, R. E.; Fok, M.-C.; Deng, Y.; Wiltberger, M.; Lyon, J.

2010-01-01

Magnetic flux circulation is a primary mode of energy transfer from the solar wind into the ionosphere and inner magnetosphere. For southward interplanetary magnetic field (IMF), magnetic flux circulation is described by the Dungey cycle (dayside merging, night side reconnection, and magnetospheric convection), and both the ionosphere and inner magnetosphere receive energy. For dawn-dusk oriented IMF, magnetic flux circulation is not well understood, and the inner magnetosphere does not receive energy. Several models have been suggested for possible reconnection patterns; the general pattern is: dayside merging; reconnection on the dayside or along the dawn/dusk regions; and, return flow on dayside only. These models are consistent with the lack of energy in the inner magnetosphere. We will present evidence that the Dungey cycle does not explain the energy transfer during dawn-dusk oriented IMF. We will also present evidence of how magnetic flux does circulate during dawn-dusk oriented IMF, specifically how the magnetic flux reconnects and circulates back.

The annual cycle of pressure on Mars measured by Viking landers 1 and 2

NASA Technical Reports Server (NTRS)

Hess, S. L.; Ryan, J. A.; Tillman, J. E.; Henry, R. M.; Leovy, C. B.

1980-01-01

Daily mean atmospheric pressures at the two Viking landers are presented for slightly more than a Martian year. The seasonal variation of pressure owing to exchange of CO2 with the polar caps is quite evident and contradicts, in part, earlier theoretical results. Day-to-day variations are the result of passage of synoptic-scale high and low pressure systems and are an important clue to the general circulation of the atmosphere. The effects of global dust storms on the general circulation and on the diurnal variation of pressure are detected and interpreted.

Computational design of the basic dynamical processes of the UCLA general circulation model

NASA Technical Reports Server (NTRS)

Arakawa, A.; Lamb, V. R.

1977-01-01

The 12-layer UCLA general circulation model encompassing troposphere and stratosphere (and superjacent 'sponge layer') is described. Prognostic variables are: surface pressure, horizontal velocity, temperature, water vapor and ozone in each layer, planetary boundary layer (PBL) depth, temperature, moisture and momentum discontinuities at PBL top, ground temperature and water storage, and mass of snow on ground. Selection of space finite-difference schemes for homogeneous incompressible flow, with/without a free surface, nonlinear two-dimensional nondivergent flow, enstrophy conserving schemes, momentum advection schemes, vertical and horizontal difference schemes, and time differencing schemes are discussed.

Maintenance of Summer Monsoon Circulations: A Planetary-Scale Perspective.

NASA Astrophysics Data System (ADS)

Chen, Tsing-Chang

2003-06-01

The monsoon circulation, which is generally considered to be driven by the landmass-ocean thermal contrast, like a gigantic land-sea breeze circulation, exhibits a phase reversal in its vertical structure; a monsoon high aloft over a continental thermal low is juxtaposed with a midoceanic trough underlaid by an oceanic anticyclone. This classic monsoon circulation model is well matched by the monsoon circulation depicted with the observational data prior to the First Global Atmospheric Research Program (GARP) Global Experiment (FGGE). However, synthesizing findings of the global circulation portrayed with the post-FGGE data, it was found that some basic features of major monsoon circulations in Asia, North America, South America, and Australia differ from those of the classic monsoon circulation model. Therefore, a revision of the classic monsoon theory is suggested. With four different wave regimes selected to fit the horizontal dimensions of these monsoon circulations, basic features common to all four major monsoons are illustrated in terms of diagnostic analyses of the velocity potential maintenance equation (which relates diabatic heating and velocity potential) and the streamfunction budget (which links velocity potential and streamfunction) in these wave regimes. It is shown that a monsoon circulation is actually driven by the east-west differential heating and maintained dynamically by a balance between a vorticity source and advection. This dynamic balance is reflected by a spatial quadrature relationship between the monsoon divergent circulation and the monsoon high (low) at upper (lower) levels.

Where Is the “Optimal” Fontan Hemodynamics?

PubMed Central

2017-01-01

Fontan circulation is generally characterized by high central venous pressure, low cardiac output, and slightly low arterial oxygen saturation, and it is quite different from normal biventricular physiology. Therefore, when a patient with congenital heart disease is selected as a candidate for this type of circulation, the ultimate goals of therapy consist of 2 components. One is a smooth adjustment to the new circulation, and the other is long-term circulatory stabilization after adjustment. When either of these goals is not achieved, the patient is categorized as having “failed” Fontan circulation, and the prognosis is dismal. For the first goal of smooth adjustment, a lot of effort has been made to establish criteria for patient selection and intensive management immediately after the Fontan operation. For the second goal of long-term circulatory stabilization, there is limited evidence of successful strategies for long-term hemodynamic stabilization. Furthermore, there have been no data on optimal hemodynamics in Fontan circulation that could be used as a reference for patient management. Although small clinical trials and case reports are available, the results cannot be generalized to the majority of Fontan survivors. We recently reported the clinical and hemodynamic characteristics of early and late failing Fontan survivors and their association with all-cause mortality. This knowledge could provide insight into the complex Fontan pathophysiology and might help establish a management strategy for long-term hemodynamic stabilization. PMID:29035429

Interactions Between the Thermohaline Circulation and Tropical Atlantic SST in a Coupled General Circulation Model

NASA Technical Reports Server (NTRS)

Miller, Ron; Jiang, Xing-Jian; Travis, Larry (Technical Monitor)

2001-01-01

Tropical Atlantic SST shows a (statistically well-defined) decadal time scale in a 104-year simulation of unforced variability by a coupled general circulation model (CGCM). The SST anomalies superficially resemble observed Tropical Atlantic variability (TAV), and are associated with changes in the atmospheric circulation. Brazilian rainfall is modulated with a decadal time scale, along with the strength of the Atlantic trade winds, which are associated with variations in evaporation and the net surface heat flux. However, in contrast to observed tropical Atlantic variability, the trade winds damp the associated anomalies in ocean temperature, indicating a negative feedback. Tropical SST anomalies in the CGCM, though opposed by the surface heat flux, are advected in from the Southern Hemisphere mid-latitudes. These variations modulate the strength of the thermohaline circulation (THC): warm, salty anomalies at the equator sink drawing cold, fresh mid-latitude water. Upon reaching the equator, the latter inhibit vertical overturning and advection from higher latitudes, which allows warm, salty anomalies to reform, returning the cycle to its original state. Thus, the cycle results from advection of density anomalies and the effect of these anomalies upon the rate of vertical overturning and surface advection. This decadal modulation of Tropical Atlantic SST and the thermohaline circulation is correlated with ocean heat transport to the Northern Hemisphere high latitudes and Norwegian Sea SST. Because of the central role of equatorial convection, we question whether this mechanism is present in the current climate, although we speculate that it may have operated in palaeo times, depending upon the stability of the tropical water column.

Sedimentary Rocks Associated with the Coal Seams of the Saddle Beds from the Chwałowice Trough - West Part of Upper Silesian Coal Basin / Skały Osadowe Towarzyszące Pokładom Węgla Warstw Siodłowych Niecki Chwałowickiej - Zachodnia Część Górnośląskiego Zagłębia Węglowego

NASA Astrophysics Data System (ADS)

Stanienda, Katarzyna

2015-03-01

The results of investigation of the associated rocks with the Saddle Beds Coals Seams from Chwałowice Trough were presented in this article. The results of researches show that sandstones and mudstones dominate in the investigating profile. Claystones are situated mainly in ceilings and floors of coal seams. Grains of sandstones include mainly quartz, feldspars, micas and also quartzite's and gneiss's fragments. It is also possible to observe small grains of heavy minerals. Some of sandstones present bad compactness and are destroyed during transportation. This feature is connected with presence of little quantity of cement, especially in medium grained sandstones, which include more matrix than typical cement. The cement is built mainly of clay minerals, kaolinite and illite, carbonates and chalcedony but X-ray diffraction confirmed also the presence of halite in the cement of investigated sandstones. Mudstones and claystones are composed mainly of clay minerals. It's also possible to find quartz and micas there. Higher amounts of quartz and micas are possible to find rather in mudstones. The associated rocks with the Saddle Beds Coal Seams from Chwałowice Trough include also organic matter. W artykule przedstawiono wyniki badań skał towarzyszących pokładom węgla warstw siodłowych Niecki Chwałowickiej. Wyniki badań wskazują, że w badanym profilu dominują piaskowce oraz mułowce. Iłowce natomiast występują głównie w stropach i spągach pokładów węgla. Okruchy piaskowców to głównie ziarna kwarcu, skaleni, mik oraz fragmenty kwarcytów i gnejsów. Można tu również zaobserwować drobne okruchy minerałów ciężkich. Niektóre piaskowce charakteryzują się obniżoną zwięzłością i podczas transportu ulegają rozpadowi. Cecha ta związana jest z niewielką ilością spoiwa, szczególnie w piaskowcach średnioziarnistych, w których matrix przeważa nad typowym cementem. Spoiwo zbudowane jest głównie z minerałów ilastych, takich jak kaolinit i illit, węglanów i chalcedonu, chociaż wyniki dyfraktometrii rentgenowskiej potwierdziły występowanie w spoiwie badanych piaskowców również halitu. Na podstawie składu mineralnego piaskowców, dokonano ich klasyfikacji, stosując podziały skał okruchowych Krynina (1948) i Pettijohn'a-Potter'a-Siever'a (1973). Według klasyfikacji Krynina badane piaskowce reprezentują szarogłazy (szarowaki). W klasyfikacji Pettijohn'a, próbki 6, 8 i 13 reprezentują arenity lityczne, natomiast próbki 3 i 10- waki. Mułowce i iłowce zbudowane SA głównie z minerałów ilastych. Można w nich również spotkać ziarna kwarcu oraz miki. Wyższy udział kwarcu i mik jest jednak charakterystyczny dla mułowców. Skały towarzyszące pokładom węgla warstw siodłowych Niecki Chwałowickiej zawierają również domieszki substancji organicznej.

Application of the solid phase C1q and Raji cell radioimmune assays for the detection of circulating immune complexes in glomerulonephritis.

PubMed Central

Tung, K S; Woodroffe, A J; Ahlin, T D; Williams, R C; Wilson, C B

1978-01-01

The C1q solid phase and Raji cell radioimmune assays were used to determine the frequency of detectable circulating immune complexes in patients with glomerulonephritis. In this study, 46% of 56 patients with glomerulonephritis had evidence of circulating immune complexes. More important, circulating immune complexes were associated with some, but not other, types of glomerulonephritis. Thus, immune complexes were detected in lupus glomerulonephritis (9/9 patients), rapidly progressive glomerulonephritis (5/6 patients), and acute nephritis (5/6 patients), but not in IgA-IgG glomerulonephritis (0/7 patients), or membranous glomerulonephritis (0/8 patients). The Raji cell radioimmune assay and the C1q solid phase radioimmune assay showed concordance of 79% in the detection of circulating immune complexes. Serial determinations, in general, showed either persistence of a negative or positive result of conversion of positive to negative. PMID:659639

Spectroscopic observation of 5 SN candidates

NASA Astrophysics Data System (ADS)

Elias-Rosa, N.; Pursimo, T.; Korhonen, H.; Pastorello, A.; Derlopa, the NEON school PhD students S.; Marian, V.; Scognamiglio, D.; Szigeti, L.; Cabezas, M.; Fernandes, C. S.; McWhirter, P. R.; Zervas, K.

2017-09-01

We report the spectroscopic classification of SNe 2017gla, 2017glz, 2017gop, and 2017gqq, and the verification of SN2017gmr. The targets were supplied by the following surveys: ATLAS survey, see Tonry et al. (2011, PASP, 123, 58) and Tonry et al. (ATel #8680); Pan-STARRS Survey for Transients (Chambers et al. 2016, arXiv:1612.05560, and http://pswww.ifa.hawaii.edu ), the PMO-Tsinghua Supernova Survey (PTSS, http://www.cneost.org/ptss/ ); and the D The observations were performed with the 2.56 m Nordic Optical Telescope equipped with ALFOSC (range 350-950 nm; resolution 1.4 nm FWHM).

The use of lipid-lowering therapy and effects of antihyperglycaemic therapy on lipids in subjects with type 2 diabetes with or without cardiovascular disease: a pooled analysis of data from eleven randomized trials with insulin glargine 100 U/mL.

PubMed

Hanefeld, Markolf; Traylor, Louise; Gao, Ling; Landgraf, Wolfgang

2017-05-19

Dyslipidaemia is a major contributor to the increased risk of cardiovascular disease (CVD) associated with type 2 diabetes (T2D). This study aimed to characterize the extent of lipid-lowering therapy use and its impact on lipid and glycaemic outcomes in people with T2D uncontrolled on oral agents who were enrolled in insulin glargine 100 units/mL (Gla-100) randomized controlled trials (RCTs). A post hoc patient-level pooled analysis of eleven RCTs (≥24 weeks' duration) comparing Gla-100 (±oral antidiabetes drugs [OADs]) with OADs alone in people with T2D was performed. Baseline and Week 24 or study endpoint lipid status (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C] and triglycerides) and indices of glycaemic control (glycosylated haemoglobin, fasting plasma glucose [FPG]) were examined in patient groups according to treatment received and CVD status. Lipid-lowering therapy was provided at the discretion of physicians at baseline and throughout the studies. Of the 4768 participants included in the analysis, 41% (n = 1940) received lipid-lowering therapy. Only 51% of participants with CVD (1885/3672) were treated with lipid-lowering therapy; these participants had significantly lower levels of LDL-C, HDL-C and non-HDL-C, and higher levels of triglycerides versus patients not treated with lipid-lowering therapy at baseline and study endpoint (P < 0.001 for all). Antihyperglycaemia therapy resulted in decreases in glycosylated haemoglobin (-1.4 to -1.6%) and FPG (-68.9 to -75.3 mg/dL) at Week 24. Furthermore, slight improvements in non-HDL-C (-3.9 to -9.1 mg/dL) and triglyceride levels (-25.8 to -51.2 mg/dL) were observed. Similar changes were seen irrespective of lipid-lowering therapy or CVD status. In a T2D cohort included in Gla-100 clinical studies, many participants with T2D and CVD did not receive lipid-lowering therapy, and for most categories of lipid the levels were outside the optimal range. Even in patients treated with antihyperglycaemic therapy but not lipid-lowering therapy, there were modest improvements in non-HDL-C and triglyceride levels in all participants with T2D and CVD. There is a need for increased implementation of guideline recommendations such as American College of Cardiology/American Heart Association for the management of dyslipidaemia in patients with T2D.

A dehydration mechanism for the stratosphere

NASA Technical Reports Server (NTRS)

Danielsen, E. F.

1982-01-01

Although mean circulations are generally credited with dehydration of the earth's stratosphere, convective instability in the tropics converts mean circulations to small residuals of local convective circulations. The effects of large cumulonimbus which penetrate the stratosphere and form huge anvils in the lower stratosphere are discussed with respect to hydration and dehydration of the stratosphere. Radiative heating at anvil base combined with cooling at anvil top drives a dehydration engine considered essential to explain the dry stratosphere. Seasonal and longitudinal variations in dehydration potentials are examined with maximum potential attributed to Micronesian area during winter and early spring.

Numerical Simulation in a Supercirtical CFB Boiler

NASA Astrophysics Data System (ADS)

Zhang, Yanjun; Gaol, Xiang; Luo, Zhongyang; Jiang, Xiaoguo

The dimension of the hot circulation loop of the supercritical CFB boiler is large, and there are many unknowns and challenges that should be identified and resolved during the development. In order to realize a reasonable and reliable design of the hot circulation loop, numerical simulation of gas-solid flow in a supercritical CFB boiler was conducted by using FLUENT software. The working condition of hot circulation loop flow field, gas-solid flow affected by three unsymmetrical cyclones, air distribution and pressure drop in furnace were analyzed. The simulation results showed that the general arrangement of the 600MWe supercritical CFB boiler is reasonable.

Parathyroid hormone - Secretion and metabolism in vivo.

NASA Technical Reports Server (NTRS)

Habener, J. F.; Powell, D.; Murray, T. M.; Mayer, G. P.; Potts, J. T., Jr.

1971-01-01

Gel filtration and radioimmunoassay were used to determine the molecular size and immunochemical reactivity of parathyroid hormone present in gland extracts, in the general peripheral circulation, and in parathyroid effluent blood from patients with hyperparathyroidism, as well as from calves and from cattle. It was found that parathyroid hormone secreted from the parathyroids in man and cattle is at least as large as the molecule extracted from normal bovine glands. However, once secreted into the circulation the hormone is cleaved, and one or more fragments, immunologically, dissimilar to the originally secreted hormone, constitute the dominant form of circulating immunoreactive hormone.

The response of an ocean general circulation model to surface wind stress produced by an atmospheric general circulation model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, B.; Schneider, E.K.

1995-10-01

Two surface wind stress datasets for 1979-91, one based on observations and the other from an investigation of the COLA atmospheric general circulation model (AGCM) with prescribed SST, are used to drive the GFDL ocean general circulation model. These two runs are referred to as the control and COLA experiments, respectively. Simulated SST and upper-ocean heat contents (HC) in the tropical Pacific Ocean are compared with observations and between experiments. Both simulation reproduced the observed mean SST and HC fields as well as their annual cycles realistically. Major errors common to both runs are colder than observed SST in themore » eastern equatorial ocean and HC in the western Pacific south of the equator, with errors generally larger in the COLA experiment. New errors arising from the AGCM wind forcing include higher SST near the South American coast throughout the year and weaker HC gradients along the equator in boreal spring. The former is associated with suppressed coastal upwelling by weak along shore AGCM winds, and the latter is caused by weaker equatorial easterlies in boreal spring. The low-frequency ENSO fluctuations are also realistic for both runs. Correlations between the observed and simulated SST anomalies from the COLA simulation are as high as those from the control run in the central equatorial Pacific. A major problem in the COLA simulation is the appearance of unrealistic tropical cold anomalies during the boreal spring of mature El Nino years. These anomalies propagate along the equator from the western Pacific to the eastern coast in about three months, and temporarily eliminate the warm SST and HC anomalies in the eastern Pacific. This erroneous oceanic response in the COLA simulation is caused by a reversal of the westerly wind anomalies on the equator, associated with an unrealistic southward shift of the ITCZ in boreal spring during El Nino events. 66 refs., 16 figs.« less

The Sensitivity of the Midlatitude Moist Isentropic Circulation on Both Sides of the Climate Model Hierarchy

NASA Astrophysics Data System (ADS)

Fajber, R. A.; Kushner, P. J.; Laliberte, F. B.

2017-12-01

In the midlatitude atmosphere, baroclinic eddies are able to raise warm, moist air from the surface into the midtroposphere where it condenses and warms the atmosphere through latent heating. This coupling between dynamics and moist thermodynamics motivates using a conserved moist thermodynamic variable, such as the equivalent potential temperature, to study the midlatitude circulation and associated heat transport since it implicitly accounts for latent heating. When the equivalent potential temperature is used to zonally average the circulation, the moist isentropic circulation takes the form of a single cell in each hemisphere. By utilising the statistical transformed Eulerian mean (STEM) circulation we are able to parametrize the moist isentropic circulation in terms of second order dynamic and moist thermodynamic statistics. The functional dependence of the STEM allows us to analytically calculate functional derivatives that reveal the spatially varying sensitivity of the moist isentropic circulation to perturbations in different statistics. Using the STEM functional derivatives as sensitivity kernels we interpret changes in the moist isentropic circulation from two experiments: surface heating in an idealised moist model, and a climate change scenario in a comprehensive atmospheric general circulation model. In both cases we find that the changes in the moist isentropic circulation are well predicted by the functional sensitivities, and that the total heat transport is more sensitive to changes in dynamical processes driving local changes in poleward heat transport than it is to thermodynamic and/or radiative processes driving changes to the distribution of equivalent potential temperature.

Optimisation of a parallel ocean general circulation model

NASA Astrophysics Data System (ADS)

Beare, M. I.; Stevens, D. P.

1997-10-01

This paper presents the development of a general-purpose parallel ocean circulation model, for use on a wide range of computer platforms, from traditional scalar machines to workstation clusters and massively parallel processors. Parallelism is provided, as a modular option, via high-level message-passing routines, thus hiding the technical intricacies from the user. An initial implementation highlights that the parallel efficiency of the model is adversely affected by a number of factors, for which optimisations are discussed and implemented. The resulting ocean code is portable and, in particular, allows science to be achieved on local workstations that could otherwise only be undertaken on state-of-the-art supercomputers.

Martian aeolian features and deposits - Comparisons with general circulation model results

NASA Astrophysics Data System (ADS)

Greeley, R.; Skypeck, A.; Pollack, J. B.

1993-02-01

The relationships between near-surface winds and the distribution of wind-related features are investigated by means of a general circulation model of Mars' atmosphere. Predictions of wind surface stress as a function of season and dust optical depth are used to investigate the distribution and orientation of wind streaks, yardangs, and rock abundance on the surface. The global distribution of rocks on the surface correlates well with predicted wind stress, particularly during the dust storm season. The rocky areas are sites of strong winds, suggesting that fine material is swept away by the wind, leaving rocks and coarser material behind.

Tropical disturbances in relation to general circulation modeling

NASA Technical Reports Server (NTRS)

Estoque, M. A.

1982-01-01

The initial results of an evaluation of the performance of the Goddard Laboratory of Atmospheric Simulation general circulation model depicting the tropical atmosphere during the summer are presented. Because the results show the existence of tropical wave disturbances throughout the tropics, the characteristics of synoptic disturbances over Africa were studied and a synoptic case study of a selected disturbance in this area was conducted. It is shown that the model is able to reproduce wave type synoptic disturbances in the tropics. The findings show that, in one of the summers simulated, the disturbances are predominantly closed vortices; in another summer, the predominant disturbances are open waves.

Incoming Shortwave Fluxes at the Surface--A Comparison of GCM Results with Observations.

NASA Astrophysics Data System (ADS)

Garratt, J. R.

1994-01-01

Evidence is presented that the exam surface net radiation calculated in general circulation models at continental surfaces is mostly due to excess incoming shortwave fluxes. Based on long-term observations from 22 worldwide inland stations and results from four general circulation models the overestimate in models of 20% (11 W m2) in net radiation on an annual basis compares with 6% (9 W m2) for shortwave fluxes for the same 22 locations, or 9% (18 W m2) for a larger set of 93 stations (71 having shortwave fluxes only). For annual fluxes, these differences appear to be significant.

Ensemble-Based Parameter Estimation in a Coupled General Circulation Model

DOE PAGES

Liu, Y.; Liu, Z.; Zhang, S.; ...

2014-09-10

Parameter estimation provides a potentially powerful approach to reduce model bias for complex climate models. Here, in a twin experiment framework, the authors perform the first parameter estimation in a fully coupled ocean–atmosphere general circulation model using an ensemble coupled data assimilation system facilitated with parameter estimation. The authors first perform single-parameter estimation and then multiple-parameter estimation. In the case of the single-parameter estimation, the error of the parameter [solar penetration depth (SPD)] is reduced by over 90% after ~40 years of assimilation of the conventional observations of monthly sea surface temperature (SST) and salinity (SSS). The results of multiple-parametermore » estimation are less reliable than those of single-parameter estimation when only the monthly SST and SSS are assimilated. Assimilating additional observations of atmospheric data of temperature and wind improves the reliability of multiple-parameter estimation. The errors of the parameters are reduced by 90% in ~8 years of assimilation. Finally, the improved parameters also improve the model climatology. With the optimized parameters, the bias of the climatology of SST is reduced by ~90%. Altogether, this study suggests the feasibility of ensemble-based parameter estimation in a fully coupled general circulation model.« less

Quantifying predictability variations in a low-order ocean-atmosphere model - A dynamical systems approach

NASA Technical Reports Server (NTRS)

Nese, Jon M.; Dutton, John A.

1993-01-01

The predictability of the weather and climatic states of a low-order moist general circulation model is quantified using a dynamic systems approach, and the effect of incorporating a simple oceanic circulation on predictability is evaluated. The predictability and the structure of the model attractors are compared using Liapunov exponents, local divergence rates, and the correlation and Liapunov dimensions. It was found that the activation of oceanic circulation increases the average error doubling time of the atmosphere and the coupled ocean-atmosphere system by 10 percent and decreases the variance of the largest local divergence rate by 20 percent. When an oceanic circulation develops, the average predictability of annually averaged states is improved by 25 percent and the variance of the largest local divergence rate decreases by 25 percent.

Simulation of Venus polar vortices with the non-hydrostatic general circulation model

NASA Astrophysics Data System (ADS)

Rodin, Alexander V.; Mingalev, Oleg; Orlov, Konstantin

2012-07-01

The dynamics of Venus atmosphere in the polar regions presents a challenge for general circulation models. Numerous images and hyperspectral data from Venus Express mission shows that above 60 degrees latitude atmospheric motion is substantially different from that of the tropical and extratropical atmosphere. In particular, extended polar hoods composed presumably of fine haze particles, as well as polar vortices revealing mesoscale wave perturbations with variable zonal wavenumbers, imply the significance of vertical motion in these circulation elements. On these scales, however, hydrostatic balance commonly used in the general circulation models is no longer valid, and vertical forces have to be taken into account to obtain correct wind field. We present the first non-hydrostatic general circulation model of the Venus atmosphere based on the full set of gas dynamics equations. The model uses uniform grid with the resolution of 1.2 degrees in horizontal and 200 m in the vertical direction. Thermal forcing is simulated by means of relaxation approximation with specified thermal profile and time scale. The model takes advantage of hybrid calculations on graphical processors using CUDA technology in order to increase performance. Simulations show that vorticity is concentrated at high latitudes within planetary scale, off-axis vortices, precessing with a period of 30 to 40 days. The scale and position of these vortices coincides with polar hoods observed in the UV images. The regions characterized with high vorticity are surrounded by series of small vortices which may be caused by shear instability of the zonal flow. Vertical velocity component implies that in the central part of high vorticity areas atmospheric flow is downwelling and perturbed by mesoscale waves with zonal wavenumbers 1-4, resembling observed wave structures in the polar vortices. Simulations also show the existence of areas with strong vertical flow, concentrated in spiral branches extending from low latitude to the circumpolar vortex. Qualitatively this pattern suggest that the dynamics of the polar Venus atmosphere resembles that of terrestrial hurricanes, but is characterized with preferentially poleward and downwelling motions.

Recent intensification of the Walker Circulation and the role of natural sea surface temperature variability

NASA Astrophysics Data System (ADS)

Zhao, X.; Allen, R.

2017-12-01

In a warming world, the tropical atmospheric overturning circulation-including the Walker Circulation-is expected to weaken due to thermodynamic constraints. Tropical precipitation increases at a slower rate than water vapor-which increases according to Clausius Clapeyron scaling, assuming constant relative humidity-so the tropical overturning circulation slows down. This is supported by both observations and model simulations, which show a slowdown of the Walker Circulation over the 20th century. Model projections suggest a further weakening of the Walker Circulation in the 21st century. However, over the last several decades (1979-2014), multiple observations reveal a robust strengthening of the Walker Circulation. Although coupled CMIP5 simulations are unable to reproduce this strengthening, AMIP simulations-which feature the observed evolution of SSTs-are generally able to reproduce it. Assuming the ensemble mean sea surface temperatures (SSTs) from historical CMIP5 simulations accurately represent the externally forced SST response, the observed SSTs can be decomposed into a forced and an unforced component. CAM5 AMIP-type simulations driven by the unforced component of observed SSTs reproduce the observed strengthening of the Walker Circulation. Corresponding simulations driven by the forced component of observed SSTs yield a weaker Walker Circulation. These results are consistent with the zonal tropical SST gradient and the Bjerknes feedback. The unforced component of SSTs yield an increased SST gradient over tropical Pacific (a La Nina like pattern) and strengthening of the tropical trade winds, which constitute the lower branch of the Walker Circulation. The forced component of SSTs yields a zonally uniform tropical Pacific SST warming and a marginal weakening of the Walker Circulation. Our results suggest significant modulation of the tropical Walker Circulation by natural SST variability over the last several decades.

Large-Scale Atmosphere-Ocean Coupling.

DTIC Science & Technology

1984-05-01

connection. between Pacific tropical diabatic heating anomalies and extratropical circulation system over the North Pacific from East Asia to the...and G. J. Boer, 1972: REFERENCES The General Circulation of the Tropical Atmosphere and Interaction with Extratropical Latitudes. Vol. 1. MIT Press...implications for the development of severe convective storms . Mom. We& Rev.. Chang, C.-P., and K. M. Lau, 1980: Northeasterly cold surges 167, 682-703. and

Documentation of a ground hydrology parameterization for use in the GISS atmospheric general circulation model

NASA Technical Reports Server (NTRS)

Lin, J. D.; Aleano, J.; Bock, P.

1978-01-01

The moisture transport processes related to the earth's surface relevant to the ground circulation model GCM are presented. The GHM parametrizations considered are: (1) ground wetness and soil parameters; (2) precipitation; (3) evapotranspiration; (4) surface storage of snow and ice; and (5) runout. The computational aspects of the GHM using computer programs and flow charts are described.

Global and European climate impacts of a slowdown of the AMOC in a high resolution GCM

NASA Astrophysics Data System (ADS)

Jackson, L. C.; Kahana, R.; Graham, T.; Ringer, M. A.; Woollings, T.; Mecking, J. V.; Wood, R. A.

2015-12-01

The impacts of a hypothetical slowdown in the Atlantic Meridional Overturning Circulation (AMOC) are assessed in a state-of-the-art global climate model (HadGEM3), with particular emphasis on Europe. This is the highest resolution coupled global climate model to be used to study the impacts of an AMOC slowdown so far. Many results found are consistent with previous studies and can be considered robust impacts from a large reduction or collapse of the AMOC. These include: widespread cooling throughout the North Atlantic and northern hemisphere in general; less precipitation in the northern hemisphere midlatitudes; large changes in precipitation in the tropics and a strengthening of the North Atlantic storm track. The focus on Europe, aided by the increase in resolution, has revealed previously undiscussed impacts, particularly those associated with changing atmospheric circulation patterns. Summer precipitation decreases (increases) in northern (southern) Europe and is associated with a negative summer North Atlantic Oscillation signal. Winter precipitation is also affected by the changing atmospheric circulation, with localised increases in precipitation associated with more winter storms and a strengthened winter storm track. Stronger westerly winds in winter increase the warming maritime effect while weaker westerlies in summer decrease the cooling maritime effect. In the absence of these circulation changes the cooling over Europe's landmass would be even larger in both seasons. The general cooling and atmospheric circulation changes result in weaker peak river flows and vegetation productivity, which may raise issues of water availability and crop production.

Stationary eddies in the Mars general circulation as simulated by the NASA-Ames GCM

NASA Technical Reports Server (NTRS)

Barnes, J. R.; Pollack, J. B.; Haberle, Robert M.

1993-01-01

Quasistationary eddies are prominent in a large set of simulations of the Mars general circulation performed with the NASA-Ames GCM. Various spacecraft observations have at least hinted at the existence of such eddies in the Mars atmosphere. The GCM stationary eddies appear to be forced primarily by the large Mars topography, and (to a much lesser degree) by spatial variations in the surface albedo and thermal inertia. The stationary eddy circulations exhibit largest amplitudes at high altitudes (above 30-40 km) in the winter extratropical regions. In these regions they are of planetary scale, characterized largely by zonal wavenumbers 1 and 2. Southern Hemisphere winter appears to be dominated by a very strong wave 1 pattern, with both waves 1 and 2 being prominent in the Northern Hemisphere winter regime. This difference seems to be basically understandable in terms of differences in the topography in the two hemispheres. The stationary eddies in the northern winter extratropics are found to increase in amplitude with dust loading. This behavior appears to be at least partly associated with changes in the structure of the zonal-mean flow that favor a greater response to wave 1 topographic forcing. There are also strong stationary eddy circulations in the tropics and in the summer hemisphere. The eddies in the summer subtropics and extratropics arc substantially stronger in southern summer than in northern summer. The summer hemisphere stationary circulations are relatively shallow and are characterized by smaller zonal scales than those in the winter extratropics.

Simulating pathways of subsurface oil in the Faroe-Shetland Channel using an ocean general circulation model.

PubMed

Main, C E; Yool, A; Holliday, N P; Popova, E E; Jones, D O B; Ruhl, H A

2017-01-15

Little is known about the fate of subsurface hydrocarbon plumes from deep-sea oil well blowouts and their effects on processes and communities. As deepwater drilling expands in the Faroe-Shetland Channel (FSC), oil well blowouts are a possibility, and the unusual ocean circulation of this region presents challenges to understanding possible subsurface oil pathways in the event of a spill. Here, an ocean general circulation model was used with a particle tracking algorithm to assess temporal variability of the oil-plume distribution from a deep-sea oil well blowout in the FSC. The drift of particles was first tracked for one year following release. Then, ambient model temperatures were used to simulate temperature-mediated biodegradation, truncating the trajectories of particles accordingly. Release depth of the modeled subsurface plumes affected both their direction of transport and distance travelled from their release location, and there was considerable interannual variability in transport. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combination of Kinematics with Flow Visualization to Compute Total Circulation

NASA Technical Reports Server (NTRS)

Brasseur, J. G; Chang, I-Dee

1981-01-01

A method is described in which kinematics is exploited to compute the total circulation of a vortex from relatively simple flow visualization experiments. There are several advantages in the technique, including the newly acquired ability to calculate the changes in strength of a single vortex as it evolves. The main concepts and methodology are discussed in a general way for application to vortices which carry along with them definable regions of essentially irrotational fluid; however, the approach might be generalized to other flows which contain regions of concentrated vorticity. As an illustrative example, an application to the study of the transient changes in total circulation of individual vortex rings as they travel up a tube is described, taking into account the effect of the tube boundary. The accuracy of the method, assessed in part by a direct comparison with a laser Doppler measurement is felt to be well within experimental precision for vortex rings over a wide range of Reynolds numbers.

Stable isotopes of fossil teeth corroborate key general circulation model predictions for the Last Glacial Maximum in North America

NASA Astrophysics Data System (ADS)

Kohn, Matthew J.; McKay, Moriah

2010-11-01

Oxygen isotope data provide a key test of general circulation models (GCMs) for the Last Glacial Maximum (LGM) in North America, which have otherwise proved difficult to validate. High δ18O pedogenic carbonates in central Wyoming have been interpreted to indicate increased summer precipitation sourced from the Gulf of Mexico. Here we show that tooth enamel δ18O of large mammals, which is strongly correlated with local water and precipitation δ18O, is lower during the LGM in Wyoming, not higher. Similar data from Texas, California, Florida and Arizona indicate higher δ18O values than in the Holocene, which is also predicted by GCMs. Tooth enamel data closely validate some recent models of atmospheric circulation and precipitation δ18O, including an increase in the proportion of winter precipitation for central North America, and summer precipitation in the southern US, but suggest aridity can bias pedogenic carbonate δ18O values significantly.

A Pacific Ocean general circulation model for satellite data assimilation

NASA Technical Reports Server (NTRS)

Chao, Y.; Halpern, D.; Mechoso, C. R.

1991-01-01

A tropical Pacific Ocean General Circulation Model (OGCM) to be used in satellite data assimilation studies is described. The transfer of the OGCM from a CYBER-205 at NOAA's Geophysical Fluid Dynamics Laboratory to a CRAY-2 at NASA's Ames Research Center is documented. Two 3-year model integrations from identical initial conditions but performed on those two computers are compared. The model simulations are very similar to each other, as expected, but the simulations performed with the higher-precision CRAY-2 is smoother than that with the lower-precision CYBER-205. The CYBER-205 and CRAY-2 use 32 and 64-bit mantissa arithmetic, respectively. The major features of the oceanic circulation in the tropical Pacific, namely the North Equatorial Current, the North Equatorial Countercurrent, the South Equatorial Current, and the Equatorial Undercurrent, are realistically produced and their seasonal cycles are described. The OGCM provides a powerful tool for study of tropical oceans and for the assimilation of satellite altimetry data.

Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke

PubMed Central

Kilarski, Laura L.; Rutten-Jacobs, Loes C. A.; Bevan, Steve; Baker, Rob; Hassan, Ahamad; Hughes, Derralynn A.; Markus, Hugh S.

2015-01-01

Background and Purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. We determined the prevalence in a well-defined, MRI-verified cohort of apparently sporadic patients with lacunar infarct. Methods Caucasian patients with lacunar infarction, aged ≤70 years (mean age 56.7 (SD8.6)), were recruited from 72 specialist stroke centres throughout the UK as part of the Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic cause of stroke were excluded. All MRI’s and clinical histories were reviewed centrally. Screening was performed for NOTCH3 and GLA mutations. Results Of 994 subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All five patients had confluent leukoaraiosis (Fazekas grade ≥2). CADASIL prevalence overall was 0.5% (95% CI 0.2%-1.1%) and among cases with confluent leukoaraiosis 1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one patient had a missense mutation (R118C), associated with late-onset FD. Conclusion CADASIL cases are rare and only detected in SVD patients with confluent leukoaraiosis. No definite FD cases were detected. PMID:26305465

Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry☆

PubMed Central

Elliott, Susan; Buroker, Norman; Cournoyer, Jason J.; Potier, Anna M.; Trometer, Joseph D.; Elbin, Carole; Schermer, Mack J.; Kantola, Jaana; Boyce, Aaron; Turecek, Frantisek; Gelb, Michael H.; Scott, C. Ronald

2017-01-01

Background There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. Objective To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic activity assay of 6 lysosomal enzymes in a NBS laboratory for the identification of newborns at risk for developing Pompe, Mucopolysaccharidosis-I (MPS-I), Fabry, Gaucher, Niemann Pick-A/B, and Krabbe diseases. Methods and Results Enzyme activities (acid α-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), α-galactosidase A (GLA), α-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk. The 6-plex assay was efficiently performed in the Washington state NBS laboratory by a single laboratory technician at the bench using a single MS/MS instrument. The number of screen positive samples per 100,000 newborns were as follows: GAA (4.5), IDUA (13.6), GLA (18.2), SMPD1 (11.4), GBA (6.8), and GALC (25.0). Discussion A 6-plex MS/MS assay for 6 lysosomal enzymes can be successfully performed in a NBS laboratory. The analytical ranges (enzyme-dependent assay response for the quality control HIGH sample divided by that for all enzyme-independent processes) for the 6-enzymes with the MS/MS is 5- to 15-fold higher than comparable fluorimetric assays using 4-methylumbelliferyl substrates. The rate of screen positive detection is consistently lower for the MS/MS assay compared to the fluorimetric assay using a digital microfluidics platform. PMID:27238910

Viability and Stress Response of Putative Probiotic Lactobacillus plantarum Strains in Honey Environment.

PubMed

Landry, Bemmo Kamdem Ulrich; François, Zambou Ngoufack; Wang, Rui-Yan; Taicheng, Zhu; Li, Yin

2017-12-01

Due to problem of preservation of dairy products which serve as a matrix for probiotics, it is challenging to use these probiotics as food supplements in many developing countries. To determine the suitability of the Lactobacillus strains for exploitation as probiotics in honey, we investigated the effect of their storage on the viability, functionality, and the mechanism associated with their protective effect. Three isolates obtained from our laboratory collection were identified through amplification of the 16S rRNA gene. The viability of the strains in honey at different storage conditions was studied. Three genes (hdc, gtf, and clpL) responsible for the resistance of bacteria in acidic environments were screened. SDS-PAGE analysis of total protein was performed to observe protein profile changes of the strains after exposure to honey. All the three isolates, namely, GGU, GLA51, and GLP56, were identified as Lactobacillus plantarum strains. After 28 days of storage in honey at 4 °C, viable cell concentrations of the three strains were higher than 2.04 × 10 6  CFU/ml. During the same period at room temperature, only the Lactobacillus plantarum GLP56 strain remained viable with a cell concentration of 1.86 × 10 4  CFU/ml. The clpL gene coding for ATPase was detected in all the three strains. The protein of molecular weight ~ 50 kDa was absent in the protein profile of Lactobacillus plantarum GGU after 60 days of storage in honey at 4 °C. The Lactobacillus plantarum GLP56, Lactobacillus plantarum GLA51, and Lactobacillus plantarum GGU strains exposed to honey can withstand acidic environmental stress but their viability declines over time.

Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised controlled trials.

PubMed

Chan, Juliana C N; Bunnag, Pongamorn; Chan, Siew P; Tan, Iris T I; Tsai, Shih-Tzer; Gao, Ling; Landgraf, Wolfgang

2018-01-01

To compare outcomes between Asian and non-Asian patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs) initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled clinical trials. Post hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials. At baseline, Asian patients were younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from baseline (7.4% vs. 7.2%; -1.3% vs. -1.6%, respectively; P = .0001), and were less likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients. Reductions in FPG and rates of hypoglycaemia were similar between Asian and non-Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3 vs. +1.9 kg, respectively, P = .013). In our post hoc meta-analysis, Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled on OADs with similar incidence of hypoglycaemia and less absolute weight gain compared with non-Asian patients. At a similar FPG reduction, fewer Asian patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to be addressed. Copyright © 2017. Published by Elsevier B.V.

The linker connecting the two kringles plays a key role in prothrombin activation

PubMed Central

Pozzi, Nicola; Chen, Zhiwei; Pelc, Leslie A.; Shropshire, Daniel B.; Di Cera, Enrico

2014-01-01

The zymogen prothrombin is proteolytically converted by factor Xa to the active protease thrombin in a reaction that is accelerated >3,000-fold by cofactor Va. This physiologically important effect is paradigmatic of analogous cofactor-dependent reactions in the coagulation and complement cascades, but its structural determinants remain poorly understood. Prothrombin has three linkers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal protease domain (Lnk3). Recent developments indicate that the linkers, and particularly Lnk2, confer on the zymogen significant flexibility in solution and enable prothrombin to sample alternative conformations. The role of this flexibility in the context of prothrombin activation was tested with several deletions. Removal of Lnk2 in almost its entirety (ProTΔ146–167) drastically reduces the enhancement of thrombin generation by cofactor Va from >3,000-fold to 60-fold because of a significant increase in the rate of activation in the absence of cofactor. Deletion of Lnk2 mimics the action of cofactor Va and offers insights into how prothrombin is activated at the molecular level. The crystal structure of ProTΔ146–167 reveals a contorted architecture where the domains are not vertically stacked, kringle-1 comes within 9 Å of the protease domain, and the Gla-domain primed for membrane binding comes in contact with kringle-2. These findings broaden our molecular understanding of a key reaction of the blood coagulation cascade where cofactor Va enhances activation of prothrombin by factor Xa by compressing Lnk2 and morphing prothrombin into a conformation similar to the structure of ProTΔ146–167. PMID:24821807

Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

PubMed

Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J; Gardarsdottir, Marianna; Teekakirikul, Polakit; Maron, Martin; Appelbaum, Evan; Neisius, Ulf; Maron, Barry J; Burke, Michael A; Chen, Brenden; Pagant, Silvere; Madsen, Christoffer V; Danielsen, Ragnar; Arngrimsson, Reynir; Feldt-Rasmussen, Ulla; Seidman, Jonathan G; Seidman, Christine E; Gunnarsson, Gunnar Th

2017-08-01

The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities. © 2017 American Heart Association, Inc.

Biatrial reduction plasty with reef imbricate technique as an adjunct to maze procedure for permanent atrial fibrillation associated with giant left atria.

PubMed

Wang, William; Guo, L Ray; Martland, Anne Marie; Feng, Xiao-Dong; Ma, Jie; Feng, Xi Qing

2010-04-01

Success of the modified maze procedure after valvular operation with giant atria and permanent atrial fibrillation (AF) remains suboptimal. We report an aggressive approach for these patients utilizing biatrial reduction plasty with a reef imbricate suture technique concomitantly with valvular and maze procedure for AF. From January 1999 to December 2006, 122 consecutive Chinese patients with permanent AF and biatrial enlargement who required mitral valve+/-tricuspid valve (TV) surgery underwent aggressive left atrial reduction combined with radiofrequency bipolar full maze procedure. Left atrial dimensions were measured by TTE or TEE. There were 71 women (58.1%) and 51 men (41.9%) and their mean age was 45+/-9.5 years. Mean duration of AF was 48.4+/-21.4 months. All patients underwent left atrial reduction plasty with reef imbricate suture technique and full maze procedure. Their preoperative left atria measured 64+/-12 mm in the enlarged left atria (ELA) group and 86+/-17 mm in the giant left atria (GLA). Mitral valve replacement (MVR) combined with TV repair was performed in 102 patients (83%) while 21 patients underwent MVRs combined with aortic valve replacements (17%). Sixty-six (54%) patients required additional procedures and 61 (50%) of the patients also underwent left atrial appendage clot evacuation. Postoperative left atrial size was reduced to 49+/-8 mm (ELA) and 51+/-11 mm (GLA), respectively (P<0.05). Ninety-three of 122 (76%) patients were restored in normal sinus rhythm after one year clinical follow-up. Aggressive biatrial reduction plasty combined with full maze procedure is an effective treatment for patients with permanent AF undergoing concomitant valvular surgery. Further studies utilizing the reef imbricate suture technique for atrial reduction need to subsequently be evaluated.

EFFICIENCY OF BORAGE SEEDS OIL AGAINST GAMMA IRRADIATION-INDUCED HEPATOTOXICITY IN MALE RATS: POSSIBLE ANTIOXIDANT ACTIVITY.

PubMed

Khattab, Hala A H; Abdallah, Inas Z A; Yousef, Fatimah M; Huwait, Etimad A

2017-01-01

Borage ( Borago officinal L.) is an annual herbaceous plant of great interest because its oil contains a high percentage of γ-linolenic acid (GLA). The present work was carried out to detect fatty acids composition of the oil extracted from borage seeds (BO) and its potential effectiveness against γ-irradiation- induced hepatotoxicity in male rats. GC-MS analysis of fatty acids methyl esters of BO was performed to identify fatty acids composition. Sixty rats were divided into five groups (12 rats each): Control, irradiated; rats were exposed to (6.5 Gy) of whole body γ-radiation, BO (50 mg/kg b.wt), irradiated BO post-treated and irradiated BO prepost-treated. Six rats from each group were sacrificed at two time intervals 7 and 15 days post-irradiation. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) levels, lipids profile, as well as serum and hepatic reduced glutathione (GSH) and lipid peroxide (malondialdehyde) (MDA) levels were assessed. Histopathological examination of liver sections were also carried out. The results showed that the high contents of BO extracted by cold pressing, were linoleic acid (34.23%) and GLA (24.79%). Also, oral administration of BO significantly improved serum levels of liver enzymes, lipids profile, as well as serum and hepatic GSH and MDA levels (p<0.001) as compared with irradiated rats after 15 days post irradiation. Moreover, it exerted marked amelioration against irradiation-induced histopathological changes in liver tissues. The improvement was more pronounced in irradiated BO prepost-treated group than irradiated BO post-treated. BO has a beneficial role in reducing hepatotoxicity and oxidative stress induced by radiation exposure. Therefore, BO may be used as a beneficial supplement for patients during radiotherapy treatment.

Role of a cumulus parameterization scheme in simulating atmospheric circulation and rainfall in the nine-layer Goddard Laboratory for Atmospheres General Circulation Model

NASA Technical Reports Server (NTRS)

Sud, Y. C.; Chao, Winston C.; Walker, G. K.

1992-01-01

The influence of a cumulus convection scheme on the simulated atmospheric circulation and hydrologic cycle is investigated by means of a coarse version of the GCM. Two sets of integrations, each containing an ensemble of three summer simulations, were produced. The ensemble sets of control and experiment simulations are compared and differentially analyzed to determine the influence of a cumulus convection scheme on the simulated circulation and hydrologic cycle. The results show that cumulus parameterization has a very significant influence on the simulation circulation and precipitation. The upper-level condensation heating over the ITCZ is much smaller for the experiment simulations as compared to the control simulations; correspondingly, the Hadley and Walker cells for the control simulations are also weaker and are accompanied by a weaker Ferrel cell in the Southern Hemisphere. Overall, the difference fields show that experiment simulations (without cumulus convection) produce a cooler and less energetic atmosphere.

Slow and Steady: Ocean Circulation. The Influence of Sea Surface Height on Ocean Currents

NASA Technical Reports Server (NTRS)

Haekkinen, Sirpa

2000-01-01

The study of ocean circulation is vital to understanding how our climate works. The movement of the ocean is closely linked to the progression of atmospheric motion. Winds close to sea level add momentum to ocean surface currents. At the same time, heat that is stored and transported by the ocean warms the atmosphere above and alters air pressure distribution. Therefore, any attempt to model climate variation accurately must include reliable calculations of ocean circulation. Unlike movement of the atmosphere, movement of the ocean's waters takes place mostly near the surface. The major patterns of surface circulation form gigantic circular cells known as gyres. They are categorized according to their general location-equatorial, subtropical, subpolar, and polar-and may run across an entire ocean. The smaller-scale cell of ocean circulation is known' as an eddy. Eddies are much more common than gyres and much more difficult to track in computer simulations of ocean currents.

Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.

PubMed

Schurgers, Leon J; Spronk, Henri M H; Soute, Berry A M; Schiffers, Paul M; DeMey, Jo G R; Vermeer, Cees

2007-04-01

Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.

Deep circulations under simple classes of stratification

NASA Technical Reports Server (NTRS)

Salby, Murry L.

1989-01-01

Deep circulations where the motion field is vertically aligned over one or more scale heights are studied under barotropic and equivalent barotropic stratifications. The study uses two-dimensional equations reduced from the three-dimensional primitive equations in spherical geometry. A mapping is established between the full primitive equations and general shallow water behavior and the correspondence between variables describing deep atmospheric motion and those of shallow water behavior is established.

On the glacial and inter-glacial thermohaline circulation and the associated transports of heat and freshwater

NASA Astrophysics Data System (ADS)

Ballarotta, M.; Falahat, S.; Brodeau, L.; Döös, K.

2014-03-01

The change of the thermohaline circulation (THC) between the Last Glacial Maximum (LGM, ≈ 21 kyr ago) and the present day climate are explored using an Ocean General Circulation Model and stream functions projected in various coordinates. Compared to the present day period, the LGM circulation is reorganised in the Atlantic Ocean, in the Southern Ocean and particularly in the abyssal ocean, mainly due to the different haline stratification. Due to stronger wind stress, the LGM tropical circulation is more vigorous than under modern conditions. Consequently, the maximum tropical transport of heat is slightly larger during the LGM. In the North Atlantic basin, the large sea-ice extent during the LGM constrains the Gulf Stream to propagate in a more zonal direction, reducing the transport of heat towards high latitudes and reorganising the freshwater transport. The LGM circulation is represented as a large intrusion of saline Antarctic Bottom Water into the Northern Hemisphere basins. As a result, the North Atlantic Deep Water is shallower in the LGM simulation. The stream functions in latitude-salinity coordinates and thermohaline coordinates point out the different haline regimes between the glacial and interglacial period, as well as a LGM Conveyor Belt circulation largely driven by enhanced salinity contrast between the Atlantic and the Pacific basin. The thermohaline structure in the LGM simulation is the result of an abyssal circulation that lifts and deviates the Conveyor Belt cell from the area of maximum volumetric distribution, resulting in a ventilated upper layer above a deep stagnant layer, and an Atlantic circulation more isolated from the Pacific. An estimation of the turnover times reveal a deep circulation almost sluggish during the LGM, and a Conveyor Belt cell more vigorous due to the combination of stronger wind stress and shortened circulation route.

Global circulation as the main source of cloud activity on Titan

USGS Publications Warehouse

Rodriguez, S.; Le, Mouelic S.; Rannou, P.; Tobie, G.; Baines, K.H.; Barnes, J.W.; Griffith, C.A.; Hirtzig, M.; Pitman, K.M.; Sotin, Christophe; Brown, R.H.; Buratti, B.J.; Clark, R.N.; Nicholson, P.D.

2009-01-01

Clouds on Titan result from the condensation of methane and ethane and, as on other planets, are primarily structured by circulation of the atmosphere. At present, cloud activity mainly occurs in the southern (summer) hemisphere, arising near the pole and at mid-latitudes from cumulus updrafts triggered by surface heating and/or local methane sources, and at the north (winter) pole, resulting from the subsidence and condensation of ethane-rich air into the colder troposphere. General circulation models predict that this distribution should change with the seasons on a 15-year timescale, and that clouds should develop under certain circumstances at temperate latitudes (40??) in the winter hemisphere. The models, however, have hitherto been poorly constrained and their long-term predictions have not yet been observationally verified. Here we report that the global spatial cloud coverage on Titan is in general agreement with the models, confirming that cloud activity is mainly controlled by the global circulation. The non-detection of clouds at latitude 40??N and the persistence of the southern clouds while the southern summer is ending are, however, both contrary to predictions. This suggests that Titans equator-to-pole thermal contrast is overestimated in the models and that its atmosphere responds to the seasonal forcing with a greater inertia than expected. ?? 2009 Macmillan Publishers Limited. All rights reserved.

Middle Atmospheric Transport Properties of Assimilated Datasets

NASA Technical Reports Server (NTRS)

Pawson, Steven; Rood, Richard

1999-01-01

One of the most compelling reasons for performing data assimilation in the middle atmosphere is to obtain global, balanced datasets for studies of trace gas transport and chemistry. This is a major motivation behind the Goddard Earth observation System-Data Assimilation System (GEOS-DAS). Previous studies have shown that while this and other data assimilation systems can generally obtain good estimates of the extratropical rotational velocity field, the divergent part of the dynamical field is deficient; this impacts the "residual circulation" and leads to spurious trace gas transport on seasonal and interannual timescales. These problems are impacted by the quality and the method of use of the observational data and by deficiencies in the atmospheric general circulation model. Whichever the cause at any place and time, the "solution" is to introduce non-physical forcing terms into the system (the so-called incremental analysis updates); these can directly (thermal) or indirectly (mechanical) affect the residual circulation. This paper will illustrate how the divergent circulation is affected by deficiencies in both observations and models. Theoretical considerations will be illustrated with examples from the GEOS-DAS and from simplified numerical experiments. These are designed to isolate known problems, such as the inability of models to sustain a quasi-biennial oscillation and sparse observational constraints on tropical dynamics, or radiative inconsistencies in the presence of volcanic aerosols.

Middle Atmosphere Transport Properties of Assimilated Datasets

NASA Technical Reports Server (NTRS)

Pawson, Steven; Rood, Richard

1999-01-01

One of the most compelling reasons for performing data assimilation in the middle atmosphere is to obtain global, balanced datasets for studies of trace gas transport and chemistry. This is a major motivation behind the Goddard Earth observation System-Data Assimilation System (GEOS-DAS). Previous studies have shown that while this and other data assimilation systems can generally obtain good estimates of the extratropical rotational velocity field, the divergent part of the dynamical field is deficient; this impacts the "residual circulation" and leads to spurious trace gas transport on seasonal and interannual timescales. These problems are impacted by the quality and the method of use of the observational data and by deficiencies in the atmospheric general circulation model. Whichever the cause at any place and time, the "solution" is to introduce non-physical forcing terms into the system (the so-called incremental analysis updates); these can directly (thermal) or indirectly (mechanical) affect the residual circulation. This paper will illustrate how the divergent circulation is affected by deficiencies in both observations and models. Theoretical considerations will be illustrated with examples from the GEOS-DAS and from simplified numerical experiments. These are designed to isolate known problems, such as the inability of models to sustain a quasi-biennial oscillation and sparse observational constraints on tropical dynamics, or radiative inconsistencies in the presence of volcanic aerosols.

Immunity against influenza A(H1N1) infections is determined by age at the time of initial strain circulation.

PubMed

Delabre, R M; Salez, N; Lapidus, N; Lemaitre, M; Leruez-Ville, M; de Lamballerie, X; Carrat, F

2017-01-01

We explored age-dependent patterns in haemagglutination inhibition (HI) titre to seasonal [1956 A(H1N1), 1977 A(H1N1), 2007 A(H1N1)] and pandemic [A(H1N1)pdm09] influenza strains using serological data collected from an adult French influenza cohort. Subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. We explored age-related differences between strain-specific HI titres using 1053 serological samples collected over the study period from 398 unvaccinated subjects. HI titres against the tested seasonal and pandemic strains were determined using the HI technique. Geometric mean titres (GMTs) were estimated using regression models for interval-censored data. Generalized additive mixed models were fit to log-transformed HI estimates to study the relationship between HI titre and age (age at inclusion and/or age at initial strain circulation). GMT against one strain was consistently highest in the birth cohort exposed to that strain during childhood, with peak titres observed in subjects aged 7-8 years at the time of initial strain circulation. Our results complete previous findings on influenza A(H3N2) strains and identify a strain-dependent relationship between HI titre and age at initial strain circulation.

Seasonal overturning circulation in the Red Sea: 2. Winter circulation

NASA Astrophysics Data System (ADS)

Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Köhl, Armin; Gopalakrishnan, Ganesh; Rivas, David

2014-04-01

The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24°N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model's winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow.

Estimating Neutral Atmosphere Drivers using a Physical Model

DTIC Science & Technology

2009-03-30

Araujo-Pradere, M. Fedrizzi, 2007, Memory effects in the ionosphere storm response. EGU General Assembly , Vienna, Austria Codrescu, M., T.J. Fuller...Strickland, D, 2007: Application of thermospheric general circulation models for space weather operations. J. Adv. Space Res., edited by Schmidtke

Numerical simulation of terrain-induced mesoscale circulation in the Chiang Mai area, Thailand

NASA Astrophysics Data System (ADS)

Sathitkunarat, Surachai; Wongwises, Prungchan; Pan-Aram, Rudklao; Zhang, Meigen

2008-11-01

The regional atmospheric modeling system (RAMS) was applied to Chiang Mai province, a mountainous area in Thailand, to study terrain-induced mesoscale circulations. Eight cases in wet and dry seasons under different weather conditions were analyzed to show thermal and dynamic impacts on local circulations. This is the first study of RAMS in Thailand especially investigating the effect of mountainous area on the simulated meteorological data. Analysis of model results indicates that the model can reproduce major features of local circulation and diurnal variations in temperatures. For evaluating the model performance, model results were compared with observed wind speed, wind direction, and temperature monitored at a meteorological tower. Comparison shows that the modeled values are generally in good agreement with observations and that the model captured many of the observed features.

The global geochemistry of bomb-produced tritium - General circulation model compared to available observations and traditional interpretations

NASA Technical Reports Server (NTRS)

Koster, Randal D.; Broecker, Wallace S.; Jouzel, Jean; Suozzo, Robert J.; Russell, Gary L.; Rind, David

1989-01-01

Observational evidence suggests that of the tritium produced during nuclear bomb tests that has already reached the ocean, more than twice as much arrived through vapor impact as through precipitation. In the present study, the Goddard Institute for Space Studies 8 x 10 deg atmospheric general circulation model is used to simulate tritium transport from the upper atmosphere to the ocean. The simulation indicates that tritium delivery to the ocean via vapor impact is about equal to that via precipitation. The model result is relatively insensitive to several imposed changes in tritium source location, in model parameterizations, and in model resolution. Possible reasons for the discrepancy are explored.

Computer studies of baroclinic flow. [Atmospheric General Circulation Experiment

NASA Technical Reports Server (NTRS)

Gall, R.

1985-01-01

Programs necessary for computing the transition curve on the regime diagram for the atmospheric general circulation experiment (AGOE) were completed and used to determine the regime diagram for the rotating annulus and some axisymmetric flows for one possible AGOE configuration. The effect of geometrical constraints on the size of eddies developing from a basic state is being examined. In AGOE, the geometric constraint should be the width of the shear zone or the baroclinic zone. Linear and nonlinear models are to be used to examine both barotropic and baroclinic flows. The results should help explain the scale selection mechanism of baroclinic eddies in the atmosphere experimental models such as AGOE, and the multiple vortex phenomenon in tornadoes.

Interannual Variability of the Patagonian Shelf Circulation and Cross-Shelf Exchange

NASA Astrophysics Data System (ADS)

Combes, V.; Matano, R. P.

2016-02-01

Observational studies have already established the general mean circulation and hydrographic characteristics of the Patagonian shelf waters using data from in situ observation, altimetry and more recently from the Aquarius satellite sea surface salinity, but the paucity of those data in time or below the surface leave us with an incomplete picture of the shelf circulation and of its variability. This study discusses the variability of the Patagonian central shelf circulation and off-shelf transport using a high-resolution model experiment for the period 1979-2012. The model solution shows high skill in reproducing the best-known aspects of the shelf and deep-ocean circulations. This study links the variability of the central shelf circulation and off-shelf transport to the wind variability, southern shelf transport variability and large-scale current variability. We find that while the inner and central shelf circulation are principally wind driven, the contribution of the Brazil/Malvinas Confluence (BMC) variability becomes important in the outer shelf and along the shelf break. The model also indicates that whereas the location of the off-shelf transport is controlled by the BMC, its variability is modulated by the southern shelf transport. The variability of the subtropical shelf front, where the fresh southern shelf waters encounters the saline northern shelf waters, is also presented in this study.

7 CFR 58.422 - Brine tank.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURAL MARKETING ACT OF 1946 AND THE EGG PRODUCTS INSPECTION ACT (CONTINUED) GRADING AND INSPECTION, GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General... clean, well circulated, and of the proper strength and temperature for the variety of cheese being made. ...

A cyclostrophic transformed Eulerian zonal mean model for the middle atmosphere of slowly rotating planets

NASA Astrophysics Data System (ADS)

Li, K. F.; Yao, K.; Taketa, C.; Zhang, X.; Liang, M. C.; Jiang, X.; Newman, C. E.; Tung, K. K.; Yung, Y. L.

2015-12-01

With the advance of modern computers, studies of planetary atmospheres have heavily relied on general circulation models (GCMs). Because these GCMs are usually very complicated, the simulations are sometimes difficult to understand. Here we develop a semi-analytic zonally averaged, cyclostrophic residual Eulerian model to illustrate how some of the large-scale structures of the middle atmospheric circulation can be explained qualitatively in terms of simple thermal (e.g. solar heating) and mechanical (the Eliassen-Palm flux divergence) forcings. This model is a generalization of that for fast rotating planets such as the Earth, where geostrophy dominates (Andrews and McIntyre 1987). The solution to this semi-analytic model consists of a set of modified Hough functions of the generalized Laplace's tidal equation with the cyclostrohpic terms. As examples, we apply this model to Titan and Venus. We show that the seasonal variations of the temperature and the circulation of these slowly-rotating planets can be well reproduced by adjusting only three parameters in the model: the Brunt-Väisälä bouyancy frequency, the Newtonian radiative cooling rate, and the Rayleigh friction damping rate. We will also discuss the application of this model to study the meridional transport of photochemically produced tracers that can be observed by space instruments.

Wave–turbulence interaction-induced vertical mixing and its effects in ocean and climate models

PubMed Central

Qiao, Fangli; Yuan, Yeli; Deng, Jia; Dai, Dejun; Song, Zhenya

2016-01-01

Heated from above, the oceans are stably stratified. Therefore, the performance of general ocean circulation models and climate studies through coupled atmosphere–ocean models depends critically on vertical mixing of energy and momentum in the water column. Many of the traditional general circulation models are based on total kinetic energy (TKE), in which the roles of waves are averaged out. Although theoretical calculations suggest that waves could greatly enhance coexisting turbulence, no field measurements on turbulence have ever validated this mechanism directly. To address this problem, a specially designed field experiment has been conducted. The experimental results indicate that the wave–turbulence interaction-induced enhancement of the background turbulence is indeed the predominant mechanism for turbulence generation and enhancement. Based on this understanding, we propose a new parametrization for vertical mixing as an additive part to the traditional TKE approach. This new result reconfirmed the past theoretical model that had been tested and validated in numerical model experiments and field observations. It firmly establishes the critical role of wave–turbulence interaction effects in both general ocean circulation models and atmosphere–ocean coupled models, which could greatly improve the understanding of the sea surface temperature and water column properties distributions, and hence model-based climate forecasting capability. PMID:26953182

Detection of greenhouse-gas-induced climatic change. Progress report, July 1, 1994--July 31, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, P.D.; Wigley, T.M.L.

1995-07-21

The objective of this research is to assembly and analyze instrumental climate data and to develop and apply climate models as a basis for detecting greenhouse-gas-induced climatic change, and validation of General Circulation Models. In addition to changes due to variations in anthropogenic forcing, including greenhouse gas and aerosol concentration changes, the global climate system exhibits a high degree of internally-generated and externally-forced natural variability. To detect the anthropogenic effect, its signal must be isolated from the ``noise`` of this natural climatic variability. A high quality, spatially extensive data base is required to define the noise and its spatial characteristics.more » To facilitate this, available land and marine data bases will be updated and expanded. The data will be analyzed to determine the potential effects on climate of greenhouse gas and aerosol concentration changes and other factors. Analyses will be guided by a variety of models, from simple energy balance climate models to coupled atmosphere ocean General Circulation Models. These analyses are oriented towards obtaining early evidence of anthropogenic climatic change that would lead either to confirmation, rejection or modification of model projections, and towards the statistical validation of General Circulation Model control runs and perturbation experiments.« less

A cyclostrophic transformed Eulerian zonal mean model for the middle atmosphere of slowly rotating planets

NASA Astrophysics Data System (ADS)

Li, King-Fai; Yao, Kaixuan; Taketa, Cameron; Zhang, Xi; Liang, Mao-Chang; Jiang, Xun; Newman, Claire; Tung, Ka-Kit; Yung, Yuk L.

2016-04-01

With the advance of modern computers, studies of planetary atmospheres have heavily relied on general circulation models (GCMs). Because these GCMs are usually very complicated, the simulations are sometimes difficult to understand. Here we develop a semi-analytic zonally averaged, cyclostrophic residual Eulerian model to illustrate how some of the large-scale structures of the middle atmospheric circulation can be explained qualitatively in terms of simple thermal (e.g. solar heating) and mechanical (the Eliassen-Palm flux divergence) forcings. This model is a generalization of that for fast rotating planets such as the Earth, where geostrophy dominates (Andrews and McIntyre 1987). The solution to this semi-analytic model consists of a set of modified Hough functions of the generalized Laplace's tidal equation with the cyclostrohpic terms. As an example, we apply this model to Titan. We show that the seasonal variations of the temperature and the circulation of these slowly-rotating planets can be well reproduced by adjusting only three parameters in the model: the Brunt-Väisälä bouyancy frequency, the Newtonian radiative cooling rate, and the Rayleigh friction damping rate. We will also discuss an application of this model to study the meridional transport of photochemically produced tracers that can be observed by space instruments.

Mid-latitude afforestation shifts general circulation and tropical precipitation.

PubMed

Swann, Abigail L S; Fung, Inez Y; Chiang, John C H

2012-01-17

We show in climate model experiments that large-scale afforestation in northern mid-latitudes warms the Northern Hemisphere and alters global circulation patterns. An expansion of dark forests increases the absorption of solar energy and increases surface temperature, particularly in regions where the land surface is unable to compensate with latent heat flux due to water limitation. Atmospheric circulation redistributes the anomalous energy absorbed in the northern hemisphere, in particular toward the south, through altering the Hadley circulation, resulting in the northward displacement of the tropical rain bands. Precipitation decreases over parts of the Amazon basin affecting productivity and increases over the Sahel and Sahara regions in Africa. We find that the response of climate to afforestation in mid-latitudes is determined by the amount of soil moisture available to plants with the greatest warming found in water-limited regions. Mid-latitude afforestation is found to have a small impact on modeled global temperatures and on global CO(2), but regional heating from the increase in forest cover is capable of driving unintended changes in circulation and precipitation. The ability of vegetation to affect remote circulation has implications for strategies for climate mitigation.

Observational and modeling studies of heat, moisture, precipitation and global-scale circulation patterns

NASA Technical Reports Server (NTRS)

Vincent, Dayton G.

1994-01-01

This research grant was a revised version of an original proposal. The period of the grant was for three years with a six-month no-cost extension; thus, it was from 20 July 1990 to 19 January 1994. The objectives of the grant were to identify periods and locations of active convection centers, primarily over the Southern Hemisphere tropical Indian and Pacific Oceans; determine reasons for any periodic behavior found in the first objective; identify cases where subtropical jets over the South Pacific persisted for several days and examine the influences of tropical versus extra-tropical mechanisms in maintaining them; obtain estimates of precipitation by Q(sub 1) and Q(sub 2) budgets, including the importance of terms in each of the respective budgets, and compare these estimates to those obtained by other methods; and diagnose the distributions of moisture and precipitable water over the North Atlantic Ocean using routine analyses and satellite microwave data. To accomplish these objectives, we used grant funds to purchase several data sets, including the Global Precipitation Climate Project (GPCP) observations of station precipitation, ECMWF WCRP/TOGA archive two analyses for January 1985 - December 1990, ECMWF WMO analyses for January 1980 - December 1987, and OLR data for July 1974 - December 1991. We already had some SSM/I data and GLA analyses from a previous grant. In addition, to improve our computing power, we also used grant funds to purchase an IBM PS/2 with accessories, a NEC laser jet printer, and a microcomputer system for word processing. This report is organized as follows. Our research team is listed first. Section two contains a summary of our significant accomplishments; however, a detailed discussion of research results is not included since this information can be found in the accompanying reprints and preprints. Section three offers some concluding remarks, and a complete bibliographic summary is given in Section four.

Seasonal Water Transport in the Atmosphere of Mars: Applications of a Mars General Circulation Model Using Mars Global Surveyor Data

NASA Technical Reports Server (NTRS)

Hollingsworth, Jeffery L.; Bridger, Alison F. C.; Haberle, Robert M.

1999-01-01

This is a Final Report for a Joint Research Interchange (JRI) between NASA Ames Research Center and San Jose State University, Department of Meteorology. We present below a summary of progress made during the duration of this JRI. The focus of this JRI has been to investigate seasonal water vapor transport in the atmosphere of Mars and its effects on the planet's present climate. To this end, the primary task has been to adapt a new dynamical processor for the adiabatic tendencies of the atmospheric circulation into the NASA Ames Mars general circulation model (MGCM). Using identical boundary and initial conditions, several comparative tests between the new and old MGCMs have been performed and the nature of the simulated circulations have been diagnosed. With confidence that the updated version of the Ames MGCM produces quite similar mean and eddy circulation statistics, the new climate model is well poised as a tool to pursue fundamental questions related to the spatial and seasonal variations of atmospheric water vapor on Mars, and to explore exchanges of water with non-atmospheric reservoirs and transport within its atmosphere. In particular, the role of surface sources and sinks can be explored, the range of water-vapor saturation altitudes can be investigated, and plausible precipitation mechanisms can be studied, for a range of atmospheric dust loadings. Such future investigations can contribute to a comprehensive study of surface inventories, exchange mechanisms, and the relative importance of atmospheric transport Mars' water cycle. A listing of presentations made and manuscripts submitted during the course of this project is provided.

Seasonal Water Transport in the Atmosphere of Mars: Applications of a Mars General Circulation Model Using Mars Global Surveyor Data

NASA Technical Reports Server (NTRS)

Hollingsworth, Jeffery L.; Bridger, Alison F. C.; Haberle, Robert M.

1999-01-01

This is a Final Report for a Joint Research Interchange (JRI) between NASA Ames Research Center and San Jose State University, Department of Meteorology. We present below a summary of progress made during the duration of this JRI. The focus of this JRI has been to investigate seasonal water vapor transport in the atmosphere of Mars and its effects on the planet's present climate. To this end, the primary task has been to adapt a new dynamical processor for the adiabatic tendencies of the atmospheric circulation into the NASA Ames Mars general circulation model (MGCM). Using identical boundary and initial conditions, several comparative tests between the new and old MGCMs have been performed and the nature of the simulated circulations have been diagnosed. With confidence that the updated version of the Ames MGCM produces quite similar mean and eddy circulation statistics, the new climate model is well poised as a tool to pursue fundamental questions related to the spatial and seasonal variations of atmospheric water vapor on Mars, and to explore exchanges of water with non-atmospheric reservoirs and transport within its atmosphere. In particular, the role of surface sources and sinks can be explored, the range of water-vapor saturation altitudes can be investigated, and plausible precipitation mechanisms can be studied, for a range of atmospheric dust loadings, such future investigations can contribute to a comprehensive study of surface inventories, exchange mechanisms, and the relative importance of atmospheric transport Mars' water cycle. A listing of presentations made and manuscripts submitted during the course of this project is provided.

Multimillennium changes in dissolved oxygen under global warming: results from an AOGCM and offline ocean biogeochemical model

NASA Astrophysics Data System (ADS)

Yamamoto, A.; Abe-Ouchi, A.; Shigemitsu, M.; Oka, A.; Takahashi, K.; Ohgaito, R.; Yamanaka, Y.

2016-12-01

Long-term oceanic oxygen change due to global warming is still unclear; most future projections (such as CMIP5) are only performed until 2100. Indeed, few previous studies using conceptual models project oxygen change in the next thousands of years, showing persistent global oxygen reduction by about 30% in the next 2000 years, even after atmospheric carbon dioxide stops rising. Yet, these models cannot sufficiently represent the ocean circulation change: the key driver of oxygen change. Moreover, considering serious effect oxygen reduction has on marine life and biogeochemical cycling, long-term oxygen change should be projected for higher validity. Therefore, we used a coupled atmosphere-ocean general circulation model (AOGCM) and an offline ocean biogeochemical model, investigating realistic long-term changes in oceanic oxygen concentration and ocean circulation. We integrated these models for 2000 years under atmospheric CO2 doubling and quadrupling. After global oxygen reduction in the first 500 years, oxygen concentration in deep ocean globally recovers and overshoots, despite surface oxygen decrease and weaker Atlantic Meridional Overturning Circulation. Deep ocean convection in the Weddell Sea recovers and overshoots, after initial cessation. Thus, enhanced deep convection and associated Antarctic Bottom Water supply oxygen-rich surface waters to deep ocean, resulting global deep ocean oxygenation. We conclude that the change in ocean circulation in the Southern Ocean potentially drives millennial-scale oxygenation in the deep ocean; contrary to past reported long-term oxygen reduction and general expectation. In presentation, we will discuss the mechanism of response of deep ocean convection in the Weddell Sea and show the volume changes of hypoxic waters.

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses.

PubMed

Rubenstein, David A; Hom, Sarah; Ghebrehiwet, Berhane; Yin, Wei

2015-10-01

Kupffer cells are liver resident macrophages that are responsible for screening and clearing blood of pathogens and foreign particles. It has recently been shown that Kupffer cells interact with platelets, through an adhesion based mechanism, to aid in pathogen clearance and then these platelets re-enter the general systemic circulation. Thus, a mechanism has been identified that relates liver inflammation to possible changes in the systemic circulation. However, the role that Kupffer cells play in cardiovascular disease initiation/progression has not been elucidated. Thus, our objective was to determine whether or not Kupffer cells are responsive to a classical cardiovascular risk factor and if these changes can be transmitted into the general systemic circulation. If Kupffer cells initiate inflammatory responses after exposure to classical cardiovascular risk factors, then this provides a potential alternative/synergistic pathway for cardiovascular disease initiation. We aimed to elucidate the prevalence of this potential pathway. We hypothesized that Kupffer cells would initiate a robust inflammatory response after exposure to tobacco cigarette or e-cigarette products and that the inflammatory response would have the potential to antagonize other salient cells for cardiovascular disease progression. To test this, Kupffer cells were incubated with tobacco smoke extracts, e-cigarette vapor extracts or pure nicotine. Complement deposition onto Kupffer cells, Kupffer cell complement receptor expression, oxidative stress production, cytokine release and viability and density were assessed after the exposure. We observed a robust inflammatory response, oxidative stress production and cytokine release after Kupffer cells were exposed to tobacco or e-cigarette extracts. We also observed a marginal decrease in cell viability coupled with a significant decrease in cell density. In general, this was not a function of the extract formulation (e.g. tobacco vs. e-cigarette products or the formulation of the cigarette product). These results indicate that Kupffer cells are responsive to classical cardiovascular risk factors and that an inflammatory response is initiated that may pass into the general systemic circulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anisotropic Mesoscale Eddy Transport in Ocean General Circulation Models

NASA Astrophysics Data System (ADS)

Reckinger, S. J.; Fox-Kemper, B.; Bachman, S.; Bryan, F.; Dennis, J.; Danabasoglu, G.

2014-12-01

Modern climate models are limited to coarse-resolution representations of large-scale ocean circulation that rely on parameterizations for mesoscale eddies. The effects of eddies are typically introduced by relating subgrid eddy fluxes to the resolved gradients of buoyancy or other tracers, where the proportionality is, in general, governed by an eddy transport tensor. The symmetric part of the tensor, which represents the diffusive effects of mesoscale eddies, is universally treated isotropically in general circulation models. Thus, only a single parameter, namely the eddy diffusivity, is used at each spatial and temporal location to impart the influence of mesoscale eddies on the resolved flow. However, the diffusive processes that the parameterization approximates, such as shear dispersion, potential vorticity barriers, oceanic turbulence, and instabilities, typically have strongly anisotropic characteristics. Generalizing the eddy diffusivity tensor for anisotropy extends the number of parameters to three: a major diffusivity, a minor diffusivity, and the principal axis of alignment. The Community Earth System Model (CESM) with the anisotropic eddy parameterization is used to test various choices for the newly introduced parameters, which are motivated by observations and the eddy transport tensor diagnosed from high resolution simulations. Simply setting the ratio of major to minor diffusivities to a value of five globally, while aligning the major axis along the flow direction, improves biogeochemical tracer ventilation and reduces global temperature and salinity biases. These effects can be improved even further by parameterizing the anisotropic transport mechanisms in the ocean.

Comparing the Degree of Land-Atmosphere Interaction in Four Atmospheric General Circulation Models

NASA Technical Reports Server (NTRS)

Koster, Randal D.; Dirmeyer, Paul A.; Hahmann, Andrea N.; Ijpelaar, Ruben; Tyahla, Lori; Cox, Peter; Suarez, Max J.; Houser, Paul R. (Technical Monitor)

2001-01-01

Land-atmosphere feedback, by which (for example) precipitation-induced moisture anomalies at the land surface affect the overlying atmosphere and thereby the subsequent generation of precipitation, has been examined and quantified with many atmospheric general circulation models (AGCMs). Generally missing from such studies, however, is an indication of the extent to which the simulated feedback strength is model dependent. Four modeling groups have recently performed a highly controlled numerical experiment that allows an objective inter-model comparison of land-atmosphere feedback strength. The experiment essentially consists of an ensemble of simulations in which each member simulation artificially maintains the same time series of surface prognostic variables. Differences in atmospheric behavior between the ensemble members then indicates the degree to which the state of the land surface controls atmospheric processes in that model. A comparison of the four sets of experimental results shows that feedback strength does indeed vary significantly between the AGCMs.

What causes Mars' annular polar vortices?

NASA Astrophysics Data System (ADS)

Toigo, A. D.; Waugh, D. W.; Guzewich, S. D.

2017-01-01

A distinctive feature of the Martian atmosphere is that the winter polar vortices exhibit annuli of high potential vorticity (PV) with a local minimum near the pole. These annuli are seen in observations, reanalyses, and free-running general circulation model simulations of Mars, but are not generally a feature of Earth's polar vortices, where there is a monotonic increase in magnitude of PV with latitude. The creation and maintenance of the annular polar vortices on Mars are not well understood. Here we use simulations with a Martian general circulation model to the show that annular vortices are related to another distinctive, and possibly unique in the solar system, feature of the Martian atmosphere: the condensation of the predominant atmospheric gas species (CO2) in polar winter regions. The latent heat associated with CO2 condensation leads to destruction of PV in the polar lower atmosphere, inducing the formation of an annular PV structure.

Spherical harmonic analysis of a synoptic climatology generated with a global general circulation model

NASA Technical Reports Server (NTRS)

Christidis, Z. D.; Spar, J.

1980-01-01

Spherical harmonic analysis was used to analyze the observed climatological (C) fields of temperature at 850 mb, geopotential height at 500 mb, and sea level pressure. The spherical harmonic method was also applied to the corresponding "model climatological" fields (M) generated by a general circulation model, the "GISS climate model." The climate model was initialized with observed data for the first of December 1976 at 00. GMT and allowed to generate five years of meteorological history. Monthly means of the above fields for the five years were computed and subjected to spherical harmonic analysis. It was found from the comparison of the spectral components of both sets, M and C, that the climate model generated reasonable 500 mb geopotential heights. The model temperature field at 850 mb exhibited a generally correct structure. However, the meridional temperature gradient was overestimated and overheating of the continents was observed in summer.

Using in-situ observations of atmospheric water vapor isotopes to benchmark and isotope-enabled General Circulation Models and improve ice core paleo-climate reconstruction

NASA Astrophysics Data System (ADS)

Steen-Larsen, Hans Christian; Sveinbjörnsdottir, Arny; Masson-Delmotte, Valerie; Werner, Martin; Risi, Camille; Yoshimura, Kei

2016-04-01

We have since 2010 carried out in-situ continuous water vapor isotope observations on top of the Greenland Ice Sheet (3 seasons at NEEM), in Svalbard (1 year), in Iceland (4 years), in Bermuda (4 years). The expansive dataset containing high accuracy and precision measurements of δ18O, δD, and the d-excess allow us to validate and benchmark the treatment of the atmospheric hydrological cycle's processes in General Circulation Models using simulations nudged to reanalysis products. Recent findings from both Antarctica and Greenland have documented strong interaction between the snow surface isotopes and the near surface atmospheric water vapor isotopes on diurnal to synoptic time scales. In fact, it has been shown that the snow surface isotopes take up the synoptic driven atmospheric water vapor isotopic signal in-between precipitation events, erasing the precipitation isotope signal in the surface snow. This highlights the importance of using General or Regional Climate Models, which accurately are able to simulate the atmospheric water vapor isotopic composition, to understand and interpret the ice core isotope signal. With this in mind we have used three isotope-enabled General Circulation Models (isoGSM, ECHAM5-wiso, and LMDZiso) nudged to reanalysis products. We have compared the simulations of daily mean isotope values directly with our in-situ observations. This has allowed us to characterize the variability of the isotopic composition in the models and compared it to our observations. We have specifically focused on the d-excess in order to characterize why both the mean and the variability is significantly lower than our observations. We argue that using water vapor isotopes to benchmark General Circulation Models offers an excellent tool for improving the treatment and parameterization of the atmospheric hydrological cycle. Recent studies have documented a very large inter-model dispersion in the treatment of the Arctic water cycle under a future global warming and greenhouse gas emission scenario. Our results call for action to create an international pan-Arctic monitoring water vapor isotope network in order to improve future projections of Arctic climate.

Fast Adjustments of the Asian Summer Monsoon to Anthropogenic Aerosols

NASA Astrophysics Data System (ADS)

Li, Xiaoqiong; Ting, Mingfang; Lee, Dong Eun

2018-01-01

Anthropogenic aerosols are a major factor contributing to human-induced climate change, particularly over the densely populated Asian monsoon region. Understanding the physical processes controlling the aerosol-induced changes in monsoon rainfall is essential for reducing the uncertainties in the future projections of the hydrological cycle. Here we use multiple coupled and atmospheric general circulation models to explore the physical mechanisms for the aerosol-driven monsoon changes on different time scales. We show that anthropogenic aerosols induce an overall reduction in monsoon rainfall and circulation, which can be largely explained by the fast adjustments over land north of 20∘N. This fast response occurs before changes in sea surface temperature (SST), largely driven by aerosol-cloud interactions. However, aerosol-induced SST feedbacks (slow response) cause substantial changes in the monsoon meridional circulation over the oceanic regions. Both the land-ocean asymmetry and meridional temperature gradient are key factors in determining the overall monsoon circulation response.

A continuum model for pressure-flow relationship in human pulmonary circulation.

PubMed

Huang, Wei; Zhou, Qinlian; Gao, Jian; Yen, R T

2011-06-01

A continuum model was introduced to analyze the pressure-flow relationship for steady flow in human pulmonary circulation. The continuum approach was based on the principles of continuum mechanics in conjunction with detailed measurement of vascular geometry, vascular elasticity and blood rheology. The pulmonary arteries and veins were considered as elastic tubes and the "fifth-power law" was used to describe the pressure-flow relationship. For pulmonary capillaries, the "sheet-flow" theory was employed and the pressure-flow relationship was represented by the "fourth-power law". In this paper, the pressure-flow relationship for the whole pulmonary circulation and the longitudinal pressure distribution along the streamlines were studied. Our computed data showed general agreement with the experimental data for the normal subjects and the patients with mitral stenosis and chronic bronchitis in the literature. In conclusion, our continuum model can be used to predict the changes of steady flow in human pulmonary circulation.

On the glacial and interglacial thermohaline circulation and the associated transports of heat and freshwater

NASA Astrophysics Data System (ADS)

Ballarotta, M.; Falahat, S.; Brodeau, L.; Döös, K.

2014-11-01

The thermohaline circulation (THC) and the oceanic heat and freshwater transports are essential for understanding the global climate system. Streamfunctions are widely used in oceanography to represent the THC and estimate the transport of heat and freshwater. In the present study, the regional and global changes of the THC, the transports of heat and freshwater and the timescale of the circulation between the Last Glacial Maximum (LGM, ≈ 21 kyr ago) and the present-day climate are explored using an Ocean General Circulation Model and streamfunctions projected in various coordinate systems. We found that the LGM tropical circulation is about 10% stronger than under modern conditions due to stronger wind stress. Consequently, the maximum tropical transport of heat is about 20% larger during the LGM. In the North Atlantic basin, the large sea-ice extent during the LGM constrains the Gulf Stream to propagate in a more zonal direction, reducing the transport of heat towards high latitudes by almost 50% and reorganising the freshwater transport. The strength of the Atlantic Meridional Overturning Circulation depends strongly on the coordinate system. It varies between 9 and 16 Sv during the LGM, and between 12 to 19 Sv for the present day. Similar to paleo-proxy reconstructions, a large intrusion of saline Antarctic Bottom Water takes place into the Northern Hemisphere basins and squeezes most of the Conveyor Belt circulation into a shallower part of the ocean. These different haline regimes between the glacial and interglacial period are illustrated by the streamfunctions in latitude-salinity coordinates and thermohaline coordinates. From these diagnostics, we found that the LGM Conveyor Belt circulation is driven by an enhanced salinity contrast between the Atlantic and the Pacific basin. The LGM abyssal circulation lifts and makes the Conveyor Belt cell deviate from the abyssal region, resulting in a ventilated upper layer above a deep stagnant layer, and an Atlantic circulation more isolated from the Pacific. An estimate of the timescale of the circulation reveals a sluggish abyssal circulation during the LGM, and a Conveyor Belt circulation that is more vigorous due to the combination of a stronger wind stress and a shortened circulation route.