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Three-dimensional numerical simulations of laminar flow around a circular cylinder with sinusoidal variation of cross-section along the spanwise direction, named ‘wavy cylinder’, are performed. A series of wavy cylinders with different combinations of dimensionless wavelength (λ/Dm) and wave amplitude (a/Dm) are studied in detail at a Reynolds number of Re = U∞Dm/ν = 100, where U∞ is the free-stream velocity and Dm is the mean diameter of a wavy cylinder. The results of variation of mean drag coefficient and root mean square (r.m.s.) lift coefficient with dimensionless wavelength show that significant reduction of mean and fluctuating force coefficients occurs at optimal dimensionless wavelengths λ/Dm of around 2.5 and 6 respectively for the different amplitudes studied. Based on the variation of flow structures and force characteristics, the dimensionless wavelength from λ/Dm = 1 to λ/Dm = 10 is classified into three wavelength regimes corresponding to three types of wake structures. The wake structures at the near wake of different wavy cylinders are captured. For all wavy cylinders, the flow separation line varies along the spanwise direction. This leads to the development of a three-dimensional free shear layer with periodic repetition along the spanwise direction. The three-dimensional free shear layer of the wavy cylinder is larger and more stable than that of the circular cylinder, and in some cases the free shear layer even does not roll up into a mature vortex street behind the cylinder. As a result, the mean drag coefficients of some of the typical wavy cylinders are less than that of a corresponding circular cylinder with a maximum drag coefficient reduction up to 18%. The r.m.s. lift coefficients are greatly reduced to practically zero at optimal wavelengths. In the laminar flow regime (60 ≤ Re ≤ 150), the values of optimal wavelength are Reynolds number dependent.

BACKGROUND: Neutrophil gelatinase–associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real‐time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail. HYPOTHESIS/OBJECTIVES: The goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease. ANIMALS: Client‐owned dogs with renal disease (57) and control dogs without any disease (12) were examined. METHODS: Serum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively. RESULTS: Serum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver‐operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time. CONCLUSION: sNGAL is a useful prognostic marker when evaluating dogs with CKD.

•A semi-synthetic typhoid conjugate vaccine.•Phase I of pectin based typhoid vaccine.•safe and immunogenic in adult volunteers. Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial. Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18–45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed. No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4-fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R2=0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults. The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. ClinicalTrial.gov identifier: NCT00277147, NIH Protocol ID number: OH06-CH-0070, FDA BB Investigation New Drug (IND) number 6989.

. We introduce a simple and sensitive technique for measuring extremely low solubilities with a small sample size and small solvent volume. This technique involves measuring the decrease in the thickness of a supported thin film after exposure to a drop of known volume of solvent and removal of the solution. The feasibility of measuring very small changes in film thickness directly translates to the ability to measure extremely low solubility while at the same time using only μL of solvent. We apply the technique to the case of polystyrene with M w values in the range 2500 g/mol to 22200 g/mol in alkane solvents and show that we can easily measure a solubility of 0.1 g/L using only 1 μ g of material and 3 μ L of solvent for each sample. Graphical abstract

The pop-up progress of the coaxial rigid rotor helicopter was decomposed into 5 stages. Quasi-steady flow assumption was adopted to analyze the helicopter performance. XH-59A helicopter was regarded as a solid body. Flow interactions between fuselage and rotor, rotor and tail were ignored. The aerodynamic performance of coaxial rotor, fuselage and horizontal tail were calculated based on Blade element moment theory, wind tunnel test data and theoretical calculation correspondingly. The Pitt/Peters inflow model was used to represent the inflow velocity on the rotor and flow interaction between upper and lower rotor were considered using interference factor. The net force and moment on the helicopter was derived and formulated into flight mechanics equations. To validate the calculation, a wind tunnel test of a coaxial rigid rotor helicopter was employed. The rotor lift coefficient, helicopter pitching and rolling moment coefficients were close to the experimental data. The controlled variables of the helicopter was composed of helicopter pitch angle (shaft angle), collective pitch, cyclic pitch of both rotors, deflection angle of the horizontal tail during the pop-up progress. The mathematical model presented in this paper provides the basic system structure to analyze the pop-up progress. The required power of the helicopter were formulated with altitude, rotor thrust, flight velocity, which help to obtain a rapid and primary evaluation of the integral performance of the progress.

Background/Objectives: There is few data on the association between dietary fiber intake and estrogen receptor (ER)/progesterone receptor (PR)-defined breast cancer risk. The present study aimed to investigate the associations between total dietary fiber and dietary fiber fractions intake and breast cancer risk by ER and PR status in a hospital-based case–control study among Chinese women. Subjects/Methods: Four hundred and thirty-eight cases with primary breast cancer were consecutively recruited from June 2007 to August 2008 and frequency matched to 438 controls by age (5-year interval) and residence (rural/urban). A validated food frequency questionnaire was used to assess the dietary intake through a face-to-face interview. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for various potential confounders. Results: A statistically significant inverse association was found between total dietary fiber and fiber fractions intake and breast cancer risk. The adjusted ORs (95% CIs) for the highest versus the lowest quartile of intake were 0.31 (0.20–0.47) for total dietary fiber, 0.73 (0.48–1.11) for soy fiber, 0.48 (0.22–0.97) for vegetable fiber and 0.54 (0.31–0.92) for fruit fiber. No association was observed for cereal fiber intake and risk. An inverse association between dietary fiber intake and breast cancer risk was observed in ER+, ER−, PR+, ER+PR+ and ER−PR+ tumors. Conclusions: Our results suggest that consumption of total dietary fiber and fiber from vegetable and fruit was inversely associated with breast cancer risk. These inverse associations were more prominent in some subtypes of ER and PR breast cancers.

Background and purpose: It has been found that 3‐hydroxy‐3‐methyl‐glutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins) exert various vascular protective effects, beyond their cholesterol‐lowering property, including inhibition of platelet‐dependent thrombus formation. The objective of the present study was to determine whether the nitric oxide (NO)/cyclic GMP‐mediated processes in platelets contribute to the anti‐aggregatory activity of simvastatin. Experimental approach: After rabbit platelets were incubated with simvastatin for 5 min, aggregation was induced and the platelet aggregation, nitric oxide synthase activity, guanylyl cyclase activity, NO and cyclic GMP formation were measured appropriately. Key results: Treatment with simvastatin concentration‐dependently inhibited platelet aggregation induced by collagen or arachidonic acid with an IC50 range of 52–158 μM. We also demonstrated that simvastatin (20–80 μM) concentration‐dependently further enhanced collagen‐induced NO and cyclic GMP formation through increasing NOS activity (from 2.64±0.12 to 3.52±0.21–5.10±0.14 μmol min−1 mg protein−1) and guanylyl cyclase activity (from 142.9±7.2 to 163.5±17.5–283.8±19.5 pmol min−1 mg protein−1) in the platelets. On the contrary, inhibition of platelet aggregation by simvastatin was markedly attenuated (by about 50%) by addition of a nitric oxide synthase inhibitor, a NO scavenger or a NO‐sensitive guanylyl cyclase inhibitor. The anti‐aggregatory effects of simvastatin were significantly increased by addition of a selective inhibitor of cyclic GMP phosphodiesterase. Conclusions and implications: Our findings indicate that enhancement of a NO/cyclic GMP‐mediated process plays an important role in the anti‐aggregatory activity of simvastatin. British Journal of Pharmacology (2008) 153, 1281–1287; doi:10.1038/bjp.2008.19; published online 11 February 2008

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is known to have a critical role in DNA double-strand break repair. We have previously reported that DNA-PKcs is activated when cells enter mitosis and functions in mitotic spindle assembly and chromosome segregation. Here we report that DNA-PKcs is the upstream regulator of the Chk2–Brca1 pathway, which impacts microtubule dynamics, kinetochore attachment and chromosomal segregation in mitosis. Downstream from Chk2, Brca1 promotes monoubiquitination of γ-tubulin to inhibit microtubule nucleation and growth. We found that DNA-PKcs is essential for mitotic Chk2 phosphorylation at Thr68. As in Chk2- and Brca1-deficient cells, loss of DNA-PKcs resulted in chromosome misalignment and lagging during anaphase owing to elevation in microtubule dynamics. Importantly, these mitotic aberrations in DNA-PKcs-defective cells were alleviated by the overexpression of phosphomimetic Chk2 or Brca1 mutant proteins but not their wild-type counterparts. Taken together, these results demonstrate that DNA-PKcs regulates mitotic spindle organization and chromosomal instability via the Chk2–Brca1 signaling pathway.

Little is known about the identity of endoplasmic reticulum (ER) export signals and how they are used to regulate the number of proteins on the cell surface. Here, we describe two ER export signals that profoundly altered the steadystate distribution of potassium channels and were required for channel localization to the plasma membrane. When transferred to other potassium channels or a G protein-coupled receptor, these ER export signals increased the number of functional proteins on the cell surface. Thus, ER export of membrane proteins is not necessarily limited by folding or assembly, but may be under the control of specific export signals.