Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene-targeted replacement mice

Scope Of the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization. Methods and results Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle. Conclusion Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele

Fluctuations of company yearly profits versus scaled revenue: Fat tail distribution of Levy type

We analyze annual revenues and earnings data for the 500 largest-revenue U.S. companies during the period 1954-2007. We find that mean year profits are proportional to mean year revenues, exception made for few anomalous years, from which we postulate a linear relation between company expected mean profit and revenue. Mean annual revenues are used to scale both company profits and revenues. Annual profit fluctuations are obtained as difference between actual annual profit and its expected mean value, scaled by a power of the revenue to get a stationary behavior as a function of revenue. We find that profit fluctuations are broadly distributed having approximate power-law tails with a Levy-type exponent $\alpha \simeq 1.7$, from which we derive the associated break-even probability distribution. The predictions are compared with empirical data.Comment: 6 pages, 6 figure

Electron-correlation effects in appearance-potential spectra of Ni

Spin-resolved and temperature-dependent appearance-potential spectra of ferromagnetic Nickel are measured and analyzed theoretically. The Lander self-convolution model which relates the line shape to the unoccupied part of the local density of states turns out to be insufficient. Electron correlations and orbitally resolved transition-matrix elements are shown to be essential for a quantitative agreement between experiment and theory.Comment: LaTeX, 6 pages, 2 eps figures included, Phys. Rev. B (in press

Single-cell analysis reveals individual spore responses to simulated space vacuum

Outer space is a challenging environment for all forms of life, and dormant spores of bacteria have been frequently used to study the survival of terrestrial life in a space journey. Previous work showed that outer space vacuum alone can kill bacterial spores. However, the responses and mechanisms of resistance of individual spores to space vacuum are unclear. Here, we examined spores’ molecular changes under simulated space vacuum (~10−5 Pa) using micro-Raman spectroscopy and found that this vacuum did not cause significant denaturation of spore protein. Then, live-cell microscopy was developed to investigate the temporal events during germination, outgrowth, and growth of individual Bacillus spores. The results showed that after exposure to simulated space vacuum for 10 days, viability of spores of two Bacillus species was reduced up to 35%, but all spores retained their large Ca2 +-dipicolinic acid depot. Some of the killed spores did not germinate, and the remaining germinated but did not proceed to vegetative growth. The vacuum treatment slowed spore germination, and changed average times of all major germination events. In addition, viable vacuum-treated spores exhibited much greater sensitivity than untreated spores to dry heat and hyperosmotic stress. Among spores’ resistance mechanisms to high vacuum, DNA-protective α/β−type small acid-soluble proteins, and non- homologous end joining and base excision repair of DNA played the most important roles, especially against multiple cycles of vacuum treatment. Overall, these results give new insight into individual spore’s responses to space vacuum and provide new techniques for microorganism analysis at the single-cell level

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Comparison of 3D transitional CFD simulations for rotating wind turbine wings with measurements:Paper

Since the investigation of van Ingen et al., attempts were undertaken to search for laminar parts within the boundary layer of wind turbines operating in the lower atmosphere with much higher turbulence levels than seen in wind tunnels or at higher altitudes where airplanes usually fly. Based on the results of the DAN-Aero experiment and the Aerodynamic Glove project, a special work package Boundary Layer Transition was embedded in IAEwind Task 29 MexNext 3rd phase (MN3). Here, we report on the results of the application of various CFD tools to predict transition on the MEXICO blade. In addition, recent results from a comparison of thermographic pictures (aimed at detecting transition) with 3D transitional CFD are included as well. The MEXICO (2006) and NEW MEXICO (2014) wind tunnel experiments on a turbine equipped with three 2.5 m blades have been described extensively in the literature. In addition, during MN3, high-frequency Kulite data from experiments were used to detect traces of transitional effects. Complementary, the following set of codes were applied to cases 1.1 and 1.2 (axial inflow with 10 m/s and 15 m/s respectively) – elsA, CFX, OpenFOAM (with 2 different turbulence/transitional models), Ellipsys, (with 2 different turbulence models and eN transition prediction tool), FLOWer and TAU – to search for detection of laminar parts by means of simulation. Obviously, the flow around a rotating blade is much more complicated than around a simple 2D section. Therefore, results for even integrated quantities like thrust and torque are varying strongly. Nevertheless, visible differences between fully turbulent and transitional set-ups are present. We discuss our findings, especially with respect to turbulence and transition models used

Microwave Assisted Synthesis of Py-Im Polyamides

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps