Numerical analysis of flow non-uniformity in the hot gas manifold of the Space Shuttle main engine

Three-dimensional viscous flow in a conceptual hot gas manifold (HGM) for the Space Shuttle Main Engine High Pressure Fuel Turbopump (SSME HPFTP) was numerically analyzed. A finite difference scheme was used to solve the Navier-Stokes equations. The exact geometry of the SSME HGM was modeled using boundary fitted curvilinear coordinates and the General Interpolants Method (GIM) code. Slight compressibility of the subsonic flow was modeled using a linearized equation of state with artificial compressibility. A time relaxation method was used to obtain a steady state solution. The feasibility and potential usefulness of computational methods in assisting the design of SSME components which involves the flow of fluids within complex geometrical shapes is demonstrated

Development of the general interpolants method for the CYBER 200 series of supercomputers

The General Interpolants Method (GIM) is a 3-D, time-dependent, hybrid procedure for generating numerical analogs of the conservation laws. This study is directed toward the development and application of the GIM computer code for fluid dynamic research applications as implemented for the Cyber 200 series of supercomputers. An elliptic and quasi-parabolic version of the GIM code are discussed. Turbulence models, algebraic and differential equations, were added to the basic viscous code. An equilibrium reacting chemistry model and an implicit finite difference scheme are also included

Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients

OBJECTIVES: The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma (PPARγ) activating properties, and to have a favorable metabolic profile. Current discussion is whether the addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic syndrome in a large observational cohort in primary care. RESEARCH DESIGN AND METHODS: Multicenter, prospective, two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the metabolic syndrome were assessed. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP) blood pressure reduction, – response, and – normalization (systolic and diastolic), changes in fasting glucose, waist circumference (abdominal obesity), serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the criteria for the metabolic syndrome. Number and nature of adverse events (AEs). RESULTS: After 9 month the use of Irbesartan in monotherapy resulted in a significant reduction of blood pressure (SBP: -26.3 ± 10.1 mmHg/DBP-13.0 ± 6.6 mmHg, both p < 0.0001) in patients with the metabolic syndrome. This was accompanied by a reduction in cardiovascular risk factors: HDL cholesterol (+3.6 ± 7.2 mg/dl in men, +3.8 ± 6.5 mg/dl in women, both p < 0.0001), serum triglycerides (-28.6 ± 52.1 mg/dl, p < 0.0001), fasting blood glucose (-8.4 ± 25.1 mg/dl, p < 0.0001) and waist circumference (-2.4 ± 11.9 cm in men, -1.2 ± 14.2 in women, both p < 0.0001) were significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome: blood pressure reduction (SBP: -27.5 ± 10.1 mmHg/DBP: -14.1 ± 6.6 mmHg, both p < 0.0001), improvement in HDL cholesterol (+4.0 ± 6.8 mg/dl in men, +3.4 ± 6.8 in women, both p < 0.0001), triglycerides (-34.1 ± 52.6 mg/dl, p < 0.0001), fasting blood glucose (-10.0 ± 24.7, p < 0.0001) and waist circumference (-3.2 ± 12.7 cm in men, -1.7 ± 14.4 in women, both p < 0.0001). Tolerability was excellent: only 0.6% of patients experienced an AE. CONCLUSION: There was a significant improvement in blood pressure and metabolic risk factors as a result of Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile

Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of patients with type 2 diabetes: An Asian perspective

Background: Microalbuminuria (MA) is a risk marker for diabetic nephropathy and cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to describe the prevalence of albuminuria, CV risk factors, and treatments for renal and CV protection in an Asian population with type 2 diabetes. Methods: This cross-sectional study conducted in eight Asian countries enrolled normotensive/hypertensive adults with type 2 diabetes without known proteinuria and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes, menstruation, pregnancy, and acute fever. A single random urinary albumin/creatinine test was carried out in all patients. Results: Of 8,561 patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (<7%) was reached in only 37% of 3,834 patients with available values. Diabetes was managed by diet alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In total, 75% did not reach target blood pressure (BP) of ≤130/80 mm Hg. Antihypertensive drugs were prescribed to 52%, with the number of drugs increasing as the level of systolic BP increased. Drugs blocking the renin-angiotensin system were most commonly prescribed, followed by calcium channel blockers. Lipid-lowering drugs and anticoagulant/antiplatelet agents were used in about 30% and 25% of patients, respectively. Conclusions: Asian patients with type 2 diabetes had a high prevalence of MA and reduced kidney function. Furthermore, BP and HbA1c control was only achieved in a minority of patients. Aggressive risk management by administration of reno- and cardioprotective treatments is urgently needed. © 2008 Mary Ann Liebert, Inc.published_or_final_versio

Purification, characterization, and cloning of a bifunctional molybdoenzyme with hydratase and alcohol dehydrogenase activity

A bifunctional hydratase/alcohol dehydrogenase was isolated from the cyclohexanol degrading bacterium Alicycliphilus denitrificans DSMZ 14773. The enzyme catalyzes the addition of water to α,β-unsaturated carbonyl compounds and the subsequent alcohol oxidation. The purified enzyme showed three subunits in SDS gel, and the gene sequence revealed that this enzyme belongs to the molybdopterin binding oxidoreductase family containing molybdopterins, FAD, and iron-sulfur clusters

Chromophobe renal cell cancer - review of the literature and potential methods of treating metastatic disease

Chromophobe renal cell carcinoma (ChRCC) is a subtype of renal cell carcinoma (RCC). ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS) for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK), vimentin, epithelial membrane antigen (EMA), CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression) in membrane of cells ChRCC

p57KIP2 control of actin cytoskeleton dynamics is responsible for its mitochondrial pro-apoptotic effect

p57 (Kip2, cyclin-dependent kinase inhibitor 1C), often found downregulated in cancer, is reported to hold tumor suppressor properties. Originally described as a cyclin-dependent kinase (cdk) inhibitor, p57KIP2 has since been shown to influence other cellular processes, beyond cell cycle regulation, including cell death and cell migration. Inhibition of cell migration by p57KIP2 is attributed to the stabilization of the actin cytoskeleton through the activation of LIM domain kinase-1 (LIMK-1). Furthermore, p57KIP2 is able to enhance mitochondrial-mediated apoptosis. Here, we report that the cell death promoting effect of p57KIP2 is linked to its effect on the actin cytoskeleton. Indeed, whereas Jasplakinolide, an actin cytoskeleton-stabilizing agent, mimicked p57KIP2's pro-apoptotic effect, destabilizing the actin cytoskeleton with cytochalsin D reversed p57KIP2's pro-apoptotic function. Conversely, LIMK-1, the enzyme mediating p57KIP2's effect on the actin cytoskeleton, was required for p57KIP2's death promoting effect. Finally, p57KIP2-mediated stabilization of the actin cytoskeleton was associated with the displacement of hexokinase-1, an inhibitor of the mitochondrial voltage-dependent anion channel, from the mitochondria, providing a possible mechanism for the promotion of the mitochondrial apoptotic cell death pathway. Altogether, our findings link together two tumor suppressor properties of p57KIP2, by showing that the promotion of cell death by p57KIP2 requires its actin cytoskeleton stabilization function

Up-Regulation of MicroRNA-21 Correlates with Lower Kidney Cancer Survival

MicroRNA-21 is up-regulated in a variety of cancers like, breast, colorectal, lung, head and neck etc. However, the regulation of miR-21 in renal cell carcinoma (RCC) has not yet been studied systematically.We measured miR-21 levels in 54 pairs of kidney cancers and their normal matched tissues by real-time PCR. The expression level of miR-21 was correlated with 5 year survival and the pathological stage. Functional studies were done after inhibiting miR-21 in RCC cell lines. We studied in vitro and in vivo effects of the chemo preventive agent genistein on miR-21 expression. In 48 cases (90%), miR-21 was increased. All patients with low miR-21 expression survived 5 years, while with high miR-21 expression, only 50% survived. Higher expression of miR-21 is associated with an increase in the stage of renal cancer. Functional studies after inhibiting miRNA-21 in RCC cell lines show cell cycle arrest, induction of apoptosis and reduced invasive and migratory capabilities. Western blot analysis showed an increase in the expression of p21 and p38 MAP kinase genes and a reduction in cyclin E2. Genistein inhibited the expression of miR-21 in A-498 cells and in the tumors formed after injecting genistein treated A-498 cells in nude mice besides inhibiting tumor formation.The current study shows a clear correlation between miR-21 expression and clinical characteristics of renal cancer. Thus we believe that miR-21 can be used as a tumor marker and its inhibition may prove to be useful in controlling cancers with up-regulated miR-21

Cisplatin-induced ototoxicity: the current state of ototoxicity monitoring in New Zealand.

Background: Many well-known pharmacologic agents have been shown to have toxic effects to the cochleo-vestibular system. Examples of such ototoxic agents include cisplatin and aminoglycoside antibiotics. Ototoxicity monitoring consists of a comprehensive pattern of audiological assessments designed to detect the onset of any hearing loss. Three main methods have emerged over the past decade, and include the basic audiological assessment, extended high frequency (EHF) audiometry, and otoacoustic emission (OAE) measurement. These measures can be used separately or in combination, depending on clinical purpose and patient considerations. It is suggested by the American Academy of Audiology Position Statement and Clinical Practice Guidelines: Ototoxicity Monitoring, that baseline testing be done in a fairly comprehensive manner, including pure-tone thresholds in both the conventional- and extended high frequency ranges, tympanometry, speech audiometry, and the testing of OAEs (AAA, 2009). Anecdotal evidence suggests that New Zealand Audiologists do not currently follow a national ototoxicity monitoring protocol. Therefore the main aim of this study was to explore the current status of ototoxicity monitoring within New Zealand. Hypothesis: It was hypothesized that hospital based Audiology departments across New Zealand each followed their own internal ototoxicity monitoring protocol based, to a large extent, on the guidelines proposed by the American Academy of Audiology and by the American Speech-Language-Hearing Association. Method: Through the use of a Telephone Interview Questionnaire, 16 charge Audiologists were interviewed to establish their current state of knowledge regarding ototoxicity monitoring at 16 out of 20 district health boards in New Zealand. Enquiries about the current systems and procedures in place at their departments together with any suggestions and recommendations to improve on these systems were made. Results: This study found that only 9 of the 16 DHBs interviewed currently follow an ototoxicity monitoring protocol. Furthermore, other than initially hypothesized the origin of the protocols followed by the remaining 7 departments were reported to have ranged from independently developed protocols to historically adopted protocols. One department implemented an adapted version of a protocol by Fausti et al. (Ear and Hearing 1999; 20(6):497-505). This diversity in origin however, does confirm our initial suspicion that no universal and standardized monitoring protocol is currently being followed by Audiologists working in the public health sector of New Zealand