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Aims. We aim to characterize the multiwavelength emission from Markarian 501 (Mrk 501), quantify the energy-dependent variability, study the potential multiband correlations, and describe the temporal evolution of the broadband emission within leptonic theoretical scenarios. Methods. We organized a multiwavelength campaign to take place between March and July of 2012. Excellent temporal coverage was obtained with more than 25 instruments, including the MAGIC, FACT and VERITAS Cherenkov telescopes, the instruments on board the Swift and Fermi spacecraft, and the telescopes operated by the GASP-WEBT collaboration. Results. Mrk 501 showed a very high energy (VHE) gamma-ray flux above 0.2 TeV of similar to 0.5 times the Crab Nebula flux (CU) for most of the campaign. The highest activity occurred on 2012 June 9, when the VHE flux was similar to 3 CU, and the peak of the high-energy spectral component was found to be at similar to 2 TeV. Both the X-ray and VHE gamma-ray spectral slopes were measured to be extremely hard, with spectral indices <2 during most of the observing campaign, regardless of the X-ray and VHE flux. This study reports the hardest Mrk 501 VHE spectra measured to date. The fractional variability was found to increase with energy, with the highest variability occurring at VHE. Using the complete data set, we found correlation between the X-ray and VHE bands; however, if the June 9 flare is excluded, the correlation disappears (significance <3 sigma) despite the existence of substantial variability in the X-ray and VHE bands throughout the campaign. Conclusions. The unprecedentedly hard X-ray and VHE spectra measured imply that their low- and high-energy components peaked above 5 keV and 0.5 TeV, respectively, during a large fraction of the observing campaign, and hence that Mrk 501 behaved like an extreme high-frequency-peaked blazar (EHBL) throughout the 2012 observing season. This suggests that being an EHBL may not be a permanent characteristic of a blazar, but rather a state which may change over time. The data set acquired shows that the broadband spectral energy distribution (SED) of Mrk 501, and its transient evolution, is very complex, requiring, within the framework of synchrotron self-Compton (SSC) models, various emission regions for a satisfactory description. Nevertheless the one-zone SSC scenario can successfully describe the segments of the SED where most energy is emitted, with a significant correlation between the electron energy density and the VHE gamma-ray activity, suggesting that most of the variability may be explained by the injection of high-energy electrons. The one-zone SSC scenario used reproduces the behavior seen between the measured X-ray and VHE gamma-ray fluxes, and predicts that the correlation becomes stronger with increasing energy of the X-rays.
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Objective: Health-related quality of life (HRQoL) is an important outcome in individuals with a high risk for cardiovascular diseases. We investigated the association of HRQoL and body mass index (BMI) as an indicator for obesity.
Design: Secondary longitudinal analysis of the ORBITAL study, an intervention study which included high-risk cardiovascular primary care patients with hypercholesterolemia and an indication for statin therapy.
Methods: HRQoL was determined with the generic Short Form (SF)-12 health status instrument. Body weight and height were assessed at baseline and at months 6, 12, 18, 24, 30, and 36. We used a linear and a linear mixed-effects regression model to investigate the association between BMI and SF-12 summary scores at baseline as well as between change in BMI and SF-12 summary scores over 3 years. We adjusted for age, sex, smoking status, and in the longitudinal analysis also for the study arm and its interaction term with time.
Results: Of the 7640 participants who completed the baseline questionnaire, 6726 participants (mean age: 61 years) were analyzed. The baseline BMI was inversely associated with physical and mental SF-12 summary scores (beta [95% CI] per 1 kg/ m(2) : -0.36 [-0.41; -0.30] and -0.05 [-0.11; -0.00], respectively). A significant association between the change in BMI and physical SF-12 summary scores over time was only present in women (-0.18 [-0.27; -0.09]) and only in obese participants (-0.19 [-0.29; -0.10]). A change in BMI was directly associated with mental SF-12 summary scores (0.12 [0.06; 0.19]) in the total population.
Conclusion: Increases in BMI were associated with decreases in physical HRQoL, particularly in obese individuals and in women. In contrast, the mental HRQoL seemed to increase with increasing BMI over time. Thus, body weight management with respect to the HRQoL should be evaluated differentially by sex and body weight status.
This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
Synchrotron radiation facilities routinely operate in a multi-bunch regime, but applications relying on time-of-flight schemes require single bunch operation. Here we show that pulse picking by resonant excitation in a storage ring creates in addition to the multi-bunch operation a distinct and separable single bunch soft X-ray source. It has variable polarization, a photon flux of up to 10(7)-10(9) ph s(-1)/0.1%BW at purity values of 10(4)-10(2) and a repetition rate of 1.25 MHz. The quasi-resonant excitation of incoherent betatron oscillations of electrons allows horizontal pulse separation at variable (also circular) polarization accessible for both, regular 30 ps pulses and ultrashort pulses of 2-3 ps duration. Combined with a new generation of angularly resolving electron spectrometers this creates unique opportunities for time-resolved photoemission studies as confirmed by time-of-flight spectra. Our pulse picking scheme is particularly suited for surface physics at diffraction-limited light sources promising ultimate spectral resolution.