Energetics of Tev Blazars and Physical Constraints on their Emission Regions

Using multi-frequency spectra from TeV blazars in quiescent states, we obtain the physical parameters of the emission region of blazars within the framework of the one-zone synchrotron self-Compton (SSC) model. We numerically calculate the steady-state energy spectra of electrons by self-consistently taking into account the effects of radiative cooling with a proper account of the Klein-Nishina effects. Here electrons are assumed to be injected with a power-law spectrum and to escape on a finite time scale, which naturally leads to the existence of a break energy scale. Although we do not use time variabilities but utilize a model of electron escape to constrain the size of the emission region, the resultant size turns out to be similar to that obtained based on time variabilities. Through detailed comparison of the predicted emission spectra with observations, we find that for Mrk 421, Mrk 501, and PKS 2155--304, the energy density of relativistic electrons is about an order of magnitude larger than that of magnetic fields with an uncertainty within a factor of a few.Comment: Accepted for publication in Ap

Stuck in the Past? Rumination-Related Memory Integration

Memories connected to ruminative concerns repetitively capture attention, even in situations designed to alter them. However, recent research on memory updating suggests that memory for benign substitutes (e.g., reinterpretations) might be facilitated by integration with the ruminative memories. As a first approach, two experiments (Ns = 72) mimicked rumination-related memories with rumination-themed stimuli and an imagery task. College undergraduates screened for ruminative status first studied and imaged ruminative cue-target word pairs, and then in a second phase they studied the same cues re-paired with benign targets (along with new and repeated pairs). On the test of cued recall of benign targets, they judged whether each recalled word had been repeated or changed across the two phases (or was new in the second phase). When target changes were not remembered, recall of benign targets revealed proactive interference that was insensitive to ruminative status. However, when participants remembered change and the ruminative targets, their recall of benign targets was facilitated, particularly if they identified as ruminators (Experiment 1). When the test simply asked for recall of either or both targets (Experiment 2), ruminators recalled both targets more frequently than did others. These outcomes suggest that ruminative memories might provide bridges to remembering associated benign memories, such as reinterpretations, under conditions consistent with everyday ruminative retrieval

Models for Nonthermal Photon Spectra

We describe models of nonthermal photon emission from a homogeneous distribution of relativistic electrons and protons. Contributions from the synchrotron, inverse Compton, nonthermal bremsstrahlung and neutral-pion decay processes are computed separately using a common parameterization of the underlying distribution of nonthermal particles. The models are intended for use in fitting spectra from multi-wavelength observations and are designed to be accurate and efficient. Although our applications have focused on Galactic supernova remnants, the software is modular, making it straightforward to customize for different applications. In particular, the shapes of the particle distribution functions and the shape of the seed photon spectrum used by the inverse Compton model are defined in separate modules and may be customized for specific applications. We assess the accuracy of these models by using a recurrence relation and by comparing them with analytic results and with previous numerical work by other authors.Comment: 14 pages, 7 figures, Accepted for publication in ApJ Supplemen

Multiwavelength observations of Mkn 501 during the 1997 high state

During the observation period 1997, the nearby Blazar Mkn 501 showed extremely strong emission and high variability. We examine multiwavelength aspects of this event using radio, optical, soft and hard X-ray and TeV data. We concentrate on the medium-timescale variability of the broadband spectra, averaged over weekly intervals. We confirm the previously found correlation between soft and hard X-ray emission and the emission at TeV energies, while the source shows only minor variability at radio and optical wavelengths. The non-linear correlation between hard X-ray and TeV fluxes is consistent with a simple analytic estimate based on an SSC model in which Klein-Nishina effects are important for the highest-energy electrons in the jet, and flux variations are caused by variations of the electron density and/or the spectral index of the electron injection spectrum. The time-averaged spectra are fitted with a Synchrotron Self-Compton (SSC) dominated leptonic jet model, using the full Klein-Nishina cross section and following the self-consistent evolution of relativistic particles along the jet, accounting for gamma-gamma absorption and pair production within the source as well as due to the intergalactic infrared background radiation. The contribution from external inverse-Compton scattering is tightly constrained by the low maximum EGRET flux and found to be negligible at TeV energies. We find that high levels of the X-ray and TeV fluxes can be explained by a hardening of the energy spectra of electrons injected at the base of the jet, in remarkable contrast to the trend found for gamma-ray flares of the flat-spectrum radio quasar PKS 0528+134.Comment: accepted for publication in ApJ, 31 pages, 11 figure

Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms.

Background: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/ DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. Methodology: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. Conclusion: Using this method, only six SNPs were needed to predict the risk types carried by .95% of CD patients. We determined that for this tagging approach the sensitivity was .0.991, specificity .0.996 and the predictive value .0.948. Our results show that this tag SNP method is very accurate an

Parsec-Scale Images of Flat-Spectrum Radio Sources in Seyfert Galaxies

We present high angular resolution (~2 mas) radio continuum observations of five Seyfert galaxies with flat-spectrum radio nuclei, using the VLBA at 8.4 GHz. The goal of the project is to test whether these flat-spectrum cores represent thermal emission from the accretion disk, as inferred previously by Gallimore et al. for NGC 1068, or non-thermal, synchrotron self-absorbed emission, which is believed to be responsible for more powerful, flat-spectrum nuclear sources in radio galaxies and quasars. In four sources (T0109-383, NGC 2110, NGC 5252, Mrk 926), the nuclear source is detected but unresolved by the VLBA, indicating brightness temperatures in excess of 10^8 K and sizes, on average, less than 1 pc. We argue that the radio emission is non-thermal and synchrotron self-absorbed in these galaxies, but Doppler boosting by relativistic outflows is not required. Synchrotron self-absorption brightness temperatures suggest intrinsic source sizes smaller than ~0.05-0.2 pc, for these four galaxies, the smallest of which corresponds to a light-crossing time of ~60 light days or 10^4 gravitational radii for a 10^8 M_sun black hole. We also present MERLIN and VLA observations of NGC 4388, which was undetected by the VLBA, and argue that the observed, flat-spectrum, nuclear radio emission in this galaxy represents optically thin, free-free radiation from dense thermal gas on scales ~0.4 to a few pc. It is notable that the two Seyfert galaxies with detected thermal nuclear radio emission (NGC 1068 and NGC 4388) both have large X-ray absorbing columns, suggesting that columns in excess of \~10^{24} cm^{-2} are needed for such disks to be detectable. (Abridged)Comment: 36 pages including 5 tables and 4 figures; accepted for publication in Ap

On the Momentum Diffusion of Radiating Ultrarelativistic Electrons in a Turbulent Magnetic Field

Here we investigate some aspects of stochastic acceleration of ultrarelativistic electrons by magnetic turbulence. In particular, we discuss the steady-state energy spectra of particles undergoing momentum diffusion due to resonant interactions with turbulent MHD modes, taking rigorously into account direct energy losses connected with different radiative cooling processes. For the magnetic turbulence we assume a given power spectrum of the type $W(k) \propto k^{-q}$. In contrast to the previous approaches, however, we assume a finite range of turbulent wavevectors $k$, consider a variety of turbulence spectral indexes $1 =< q =< 2$, and concentrate on the case of a very inefficient particle escape from the acceleration site. We find that for different cooling and injection conditions, stochastic acceleration processes tend to establish a modified ultrarelativistic Maxwellian distribution of radiating particles, with the high-energy exponential cut-off shaped by the interplay between cooling and acceleration rates. For example, if the timescale for the dominant radiative process scales with the electron momentum as $\propto p^r$, the resulting electron energy distribution is of the form $n_e(p) \propto p^2 exp[ - (1 / a) (p / p_eq)^a]$, where $a = 2-q-r$, and $p_eq$ is the equilibrium momentum defined by the balance between stochastic acceleration and energy losses timescales. We also discuss in more detail the synchrotron and inverse-Compton emission spectra produced by such an electron energy distribution, taking into account Klein-Nishina effects. We point out that the curvature of the high frequency segments of these spectra, even though being produced by the same population of electrons, may be substantially different between the synchrotron and inverse-Compton components.Comment: 42 pages, 14 figures included. Slightly modified version, accepted for publication in Ap

TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3x10-21), A928V (rs35018800, OR = 0.53, P = 1.2x10-9), and I684S (rs12720356, OR = 0.86, P = 4.6x10-7). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6x10-18), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; Pomnibus = 0.005). Finally, in a phenomewide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases

Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis

2 páginas.-- Póster presentado al 5º European Workshop on Immune-Mediated Inflammatory Diseases celebrado en Sitges (Barcelona) dxel 1 al 3 de Diciembre de 2010.-- et al.The PTPN22 gene is an important risk factor for human autoimmunity. Two PTPN22 missense-SNPs, both with functional influence, the R620W (1858C>T, rs2476601) in exon 14 and the R263Q (788G>A, rs33996649) in exon 10 have been associated with autoimmune diseases [1-4].Peer reviewe