Fabrication of 1/20th scale wind tunnel model of jaguar aircraft

Fabrication of scaled models of aircraft and other configurations for wind tunnel testing is a highly specialized task . This involves different types of precision machining operations to obtain the desired complex shapes with high levels of accuracy. Fabrication of models required for testing in the NAL wind tunnels were till recently undertaken in-house. The increased wind tunnel test requirements of various aerospace organisations in the Country, led to a substantial increase in the number of models to be fabricated. To meet the increased model fabrication work within the time frames of user organisations, it was decided to undertake part of the work in some external machine shop facilities under the broad supervision of NAL. The present exercise in among the first few attempts in that direction

Draft proposal for establishment of CNC centre at NAL

This is a proposal for setting up Computer Numerically Controlled machining facilities at N.A.L. to cater to the increasing requirements for fabrication of complex shaped and intricate/precision components for the aerospace R & D projects of the laboratory for the next 10 - year period. This fairly comprehensive document has been prepared by an internal technical committee constituted by the Director, after detailed study and discussions and covers the technical and financial aspects for setting up such facilities

Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior

Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

Abstract Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA (P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA (P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) (P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) (P = 0.003; risk ratio, 1.21). Conclusions: This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients

Prevalence of normal weight obesity and its associated cardio-metabolic risk factors - Results from the baseline data of the Kerala Diabetes Prevention Program (KDPP)

BACKGROUND: Cardiometabolic disorders are frequently observed among those who have obesity as measured by body mass index (BMI). However, there is limited data available on the cardiometabolic profile of those who are non-obese by BMI but with a high body fat percentage (BFP), a phenotype frequently observed in the Indian population. We examined the prevalence of individuals with normal weight obesity (NWO) and the cardiometabolic profile of NWO individuals at high risk for type 2 diabetes(T2D) in a south Asian population. MATERIAL AND METHODS: In the Kerala Diabetes Prevention Program, individuals aged between 30 to 60 years were screened using the Indian Diabetes Risk Score(IDRS) in 60 rural communities in the Indian state of Kerala. We used data from the baseline survey of this trial for this analysis which included 1147 eligible high diabetes risk individuals(IDRS >60). NWO was defined as BMI within the normal range and a high BFP (as per Asia-pacific ethnicity based cut-off); Non-obese (NO) as normal BMI and BFP and overtly obese (OB) as BMI ≥25 kg/m2 irrespective of the BFP. Data on demographic, clinical and biochemical characteristics were collected using standardized questionnaires and protocols. Body fat percentage was assessed using TANITA body composition analyser (model SC330), based on bioelectrical impedance. RESULTS: The mean age of participants was 47.3 ± 7.5 years and 46% were women. The proportion with NWO was 32% (n = 364; 95% CI: 29.1 to 34.5%), NO was 17% (n = 200) and OB was 51% (n = 583). Among those with NWO, 19.7% had T2D, compared to 18.7% of those who were OB (p value = 0.45) and 8% with NO (p value = 0.003). Among those with NWO, mean systolic and diastolic blood pressure were 129 ± 20; 78 ± 12 mmHg, compared to 127 ± 17; 78±11 mmHg among those with OB (p value = 0.12;0.94) and 120 ± 16; 71±10 mmHg among with NO (p value<0.001; 0.001), respectively. A similar pattern of association was observed for LDL cholesterol and triglycerides. After adjusting for other risk factors, the odds of having diabetes (OR:2.72[95% CI:1.46-5.08]) and dyslipidemia (2.37[1.55-3.64]) was significantly more in individuals with NWO as compared to non-obese individuals. CONCLUSIONS: Almost one-third of this South Asian population, at high risk for T2D, had normal weight obesity. The significantly higher cardiometabolic risk associated with increased adiposity even in lower BMI individuals has important implications for recognition in clinical practice

Structure of a highly conserved domain of rock1 required for shroom-mediated regulation of cell morphology

Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology. © 2013 Mohan et al

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05–9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34–1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59–0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD

Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to sitagliptin. The purpose of the present analysis is to update the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies.</p> <p>Methods</p> <p>The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group) or a comparator agent (placebo or an active comparator) (N = 4,817; non-exposed group). The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day) for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin). Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events.</p> <p>Results</p> <p>Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were also generally similar between the two groups, except for increased incidence rates of hypoglycemia, related to the greater use of a sulfonylurea, and diarrhea, related to the greater use of metformin, in the non-exposed group and constipation in the sitagliptin group. Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events.</p> <p>Conclusions</p> <p>In this updated pooled safety analysis of data from 10,246 patients with type 2 diabetes, sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration.</p

Generational status and duration of residence predict diabetes prevalence among Latinos: the California Men's Health Study

<p>Abstract</p> <p>Background</p> <p>Diabetes disproportionately affects Latinos. However, examining Latinos as one group obscures important intra-group differences. This study examined how generational status, duration of US residence, and language preference are associated with diabetes prevalence and to what extent these explain the higher prevalence among Latinos.</p> <p>Methods</p> <p>We determined nativity, duration of US residence, language preference, and diabetes prevalence among 11 817 Latino, 6109 black, and 52 184 white participants in the California Men's Health Study. We combined generational status and residence duration into a single migration status variable with levels: ≥ third generation; second generation; and immigrant living in the US for > 25, 16-25, 11-15, or ≤ 10 years. Language preference was defined as language in which the participant took the survey. Logistic regression models were specified to assess the associations of dependent variables with prevalent diabetes.</p> <p>Results</p> <p>Diabetes prevalence was 22%, 23%, and 11% among Latinos, blacks, and whites, respectively. In age-adjusted models, we observed a gradient of risk of diabetes by migration status among Latinos. Further adjustment for socioeconomic status, obesity and health behaviors only partially attenuated this gradient. Language preference was a weak predictor of prevalent diabetes in some models and not significant in others. In multivariate models, we found that odds of diabetes were higher among US-born Latinos than US-born blacks.</p> <p>Conclusion</p> <p>Generational status and residence duration were associated with diabetes prevalence among middle-aged Latino men in California. As the Latino population grows, the burden of diabetes-associated disease is likely to increase and demands public health attention.</p