Wave-number Selection by Target Patterns and Side Walls in Rayleigh-Benard Convection

We present experimental results for Rayleigh-Benard convection patterns in a cylindrical container with static side-wall forcing induced by a heater. This forcing stabilized a pattern of concentric rolls (a target pattern) with the central roll (the umbilicus) at the center of the cell after a jump from the conduction to the convection state. A quasi-static increase of the control parameter (epsilon) beyond 0.8 caused the umbilicus of the pattern to move off center. As observed by others, a further quasi-static increase of epsilon up to 15.6 caused a sequence of transitions. Each transition began with the displacement of the umbilicus and then proceeded with the loss of one convection roll at the umbilicus and the return of the umbilicus to a location near the center of the cell. Alternatively, with decreasing epsilon new rolls formed at the umbilicus but large umbilicus displacements did not occur. In addition to quantitative measurements of the umbilicus displacement, we determined and analyzed the entire wave-director field of each image. The wave numbers varied in the axial direction, with minima at the umbilicus and at the cell wall and a maximum at a radial position close to 2/3 Gamma. The wave numbers at the maximum showed hysteretic jumps at the transitions, but on average agreed well with the theoretical predictions for the wave numbers selected in the far field of an infinitely extended target pattern.Comment: ReVTeX, 11 pages, 16 eps figures include

Cloning, expression, purification and characterization of a DsbA-like protein from Wolbachia pipientis

Wolbachia pipientis are obligate endosymbionts that infect a wide range of insect and other arthropod species. They act as reproductive parasites by manipulating the host reproduction machinery to enhance their own transmission. This unusual phenotype is thought to be a consequence of the actions of secreted Wolbachia proteins that are likely to contain disulfide bonds to stabilize the protein structure. In bacteria, the introduction or isomerization of disulfide bonds in proteins is catalyzed by Dsb proteins. The Wolbachia genome encodes two proteins, a-DsbA1 and a-DsbA2, that might catalyze these steps. In this work we focussed on the 234 residue protein a-DsbA1; the gene was cloned and expressed in Escherichia coli, the protein was purified and its identity confirmed by mass spectrometry. The sequence identity of a-DsbA1 for both dithiol oxidants(E. coli DsbA, 12%) and disulfide isomerases(E. coli DsbC, 14%) is similar. We therefore sought to establish whether a-DsbA1 is an oxidant or an isomerase based on functional activity. The purified a-DsbA1 was active in an oxidoreductase assay but had little isomerase activity, indicating that a-DsbA1 is DsbA-like rather than DsbC-like. This work represents the first successful example of the characterization of a recombinant Wolbachia protein. Purified a-DsbA1 will now be used in further functional studies to identify protein substrates that could help explain the molecular basis for the unusual Wolbachia phenotypes, and in structural studies to explore its relationship to other disulfide oxidoreductase proteins. Copyright © 2008 Elsevier In

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data

Objective: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. Design: Cohort study emulating a comparative effectiveness trial (target trial). Setting: Linked primary care, hospital, and death data in England, 2015-21. Participants: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. Main outcome measures: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. Results: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were −2.5 mmol/mol (95% confidence interval (CI) −3.7 to −1.3) for SGLT-2 inhibitors versus sulfonylureas and −3.2 mmol/mol (−4.6 to −1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking—the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). Conclusions: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints

Iron line profiles in Suzaku spectra of bare Seyfert galaxies

We methodically model the broad-band Suzaku spectra of a small sample of six 'bare' Seyfert galaxies: Ark 120, Fairall 9, MCG-02-14-009, Mrk 335, NGC 7469 and SWIFT J2127.4+5654. The analysis of bare Seyferts allows a consistent and physical modelling of AGN due to a weak amount of any intrinsic warm absorption, removing the degeneracy between the spectral curvature due to warm absorption and the red-wing of the Fe K region. Through effective modelling of the broad-band spectrum and investigating the presence of narrow neutral or ionized emission lines and reflection from distant material, we obtain an accurate and detailed description of the Fe K line region using models such as laor, kerrdisk and kerrconv. Results suggest that ionized emission lines at 6.7 keV and 6.97 keV (particularly Fe XXVI) are relatively common and the inclusion of these lines can greatly affect the parameters obtained with relativistic models i.e. spin, emissivity, inner radius of emission and inclination. Moderately broad components are found in all objects, but typically the emission originates from tens of Rg, rather than within <6Rg of the black hole. Results obtained with kerrdisk line profiles suggest an average emissivity of q~2.3 at intermediate spin values with all objects ruling out the presence of a maximally spinning black hole at the 90% confidence level. We also present new spin constraints for Mrk 335 and NGC 7469 with intermediate values of a=0.70(+0.12,-0.01) and a=0.69(+0.09,-0.09) respectively.Comment: 19 pages, 7 figures, 9 tables, MNRAS accepte

One-year outcomes of coronary artery bypass graft surgery versus percutaneous coronary intervention with multiple stenting for multisystem disease: A meta-analysis of individual patient data from randomized clinical trials

BackgroundWe aimed to provide a quantitative analysis of the 1-year clinical outcomes of patients with multisystem coronary artery disease who were included in recent randomized trials of percutaneous coronary intervention with multiple stenting versus coronary artery bypass graft surgery.MethodsAn individual patient database was composed of 4 trials (Arterial Revascularization Therapies Study, Stent or Surgery Trial, Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease 2, and Medicine, Angioplasty, or Surgery Study 2) that compared percutaneous coronary intervention with multiple stenting (N = 1518) versus coronary artery bypass graft surgery (N = 1533). The primary clinical end point of this study was the combined incidence of death, myocardial infarction, and stroke at 1 year after randomization. Secondary combined end points included the incidence of repeat revascularization at 1 year. All analyses were based on the intention-to-treat principle.ResultsAfter 1 year of follow-up, 8.7% of patients randomized to percutaneous coronary intervention with multiple stenting versus 9.1% of patients randomized to coronary artery bypass graft surgery reached the primary clinical end point (hazard ratio 0.95 and 95% confidence interval 0.74’1.2). Repeat revascularization procedures occurred more frequently in patients allocated to percutaneous coronary intervention with multiple stenting compared with coronary artery bypass graft surgery (18% vs 4.4%; hazard ratio 4.4 and 95% confidence interval 3.3’5.9). The percentage of patients who were free from angina was slightly lower after percutaneous coronary intervention with multiple stenting than after coronary artery bypass graft surgery (77% vs 82%; P = .002).ConclusionsOne year after the initial procedure, percutaneous coronary intervention with multiple stenting and coronary artery bypass graft surgery provided a similar degree of protection against death, myocardial infarction, or stroke for patients with multisystem disease. Repeat revascularization procedures remain high after percutaneous coronary intervention, but the difference with coronary artery bypass graft surgery has narrowed in the era of stenting

Long-Term Effects of Self-Control on Alcohol Use and Sexual Behavior among Urban Minority Young Women

High risk alcohol use and sexual behaviors peak in young adulthood and often occur in the same individuals. Alcohol use has been found to impair decision-making and contribute to high risk sexual activity. However, the association between alcohol use and risky sexual behavior may also reflect enduring individual differences in risk taking, sociability, self-control, and related variables. Both behaviors can serve similar functions related to recreation, interpersonal connection, and the pursuit of excitement or pleasure. The present study examined the extent to which high risk drinking and sexual behavior clustered together in a sample of urban minority young adult women, a demographic group at elevated risk for negative outcomes related to sexual health. We tested whether psychosocial functioning measured at the beginning of high school predicted classes of risk behaviors when girls were tracked longitudinally into young adulthood. Latent class analysis indicated three distinct profiles based on high risk drinking and sexual behavior (i.e., multiple sex partners) in young adulthood. The largest class (73% of the sample) reported low levels of risky drinking and sexual behavior. The next largest class (19%) reported high risk drinking and low risk sexual behavior, and the smallest class (8%) reported high levels of both behaviors. Compared to women from other racial/ethnic groups, black women were more likely to be categorized in the high risk drinking/low risk sex class. Multinomial logistic regression indicated that self-control in adolescence had a broad and enduring protective effect on risk behaviors eight years later and was associated with a greater probability of being in the low risk drinking/low risk sex class. Findings are discussed in terms of understanding the phenotypic expressions of risk behavior as they relate to early psychosocial development and the long-term protective function of self-control in reducing high risk drinking and sexual behaviors

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies