A magnetic white dwarf in a detached eclipsing binary

SDSS J030308.35+005444.1 is a close, detached, eclipsing white dwarf plus M dwarf binary which shows a large infrared excess which has been interpreted in terms of a circumbinary dust disc. In this paper, we present optical and near-infrared photometric and spectroscopic data for this system. At optical wavelengths, we observe heated pole caps from the white dwarf caused by accretion of wind material from the main-sequence star on to the white dwarf. At near-infrared wavelengths, we see the eclipse of two poles on the surface of the white dwarf by the main-sequence star indicating that the white dwarf is magnetic. Our spectroscopic observations reveal Zeeman-split emission lines in the hydrogen Balmer series, which we use to measure the magnetic field strength as 8 MG. This measurement indicates that the cyclotron lines are located in the infrared, naturally explaining the infrared excess without the need for a circumbinary dust disc. We also detect magnetically confined material located roughly midway between the two stars. Using measurements of the radial velocity amplitude and rotational broadening of the M star, we constrain the physical parameters of the system, a first for a magnetic white dwarf, and the location of the poles on the surface of the white dwarf. SDSS J030308.35+005444.1 is a pre-cataclysmic variable that will likely evolve into an intermediate polar in ∼1 Gyr

European clinical guidelines for Tourette syndrome and other tic disorders—version 2.0. Part III: pharmacological treatment

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients’ self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient’s needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician’s preferences, experience, and local regulatory requirements

A precision study of two eclipsing white dwarf plus M dwarf binaries

We use a combination of X-shooter spectroscopy, ULTRACAM high-speed photometry and SOFI near-infrared photometry to measure the masses and radii of both components of the eclipsing post common envelope binaries SDSS J1212-0123 and GK Vir. For both systems we measure the gravitational redshift of the white dwarf and combine it with light curve model fits to determine the inclinations, masses and radii. For SDSS J1212-0123 we find a white dwarf mass and radius of 0.439 +/- 0.002 Msun and 0.0168 +/- 0.0003 Rsun, and a secondary star mass and radius of 0.273 +/- 0.002 Msun and 0.306 +/- 0.007 Rsun. For GK Vir we find a white dwarf mass and radius of 0.564 +/- 0.014 Msun and 0.0170 +/- 0.0004 Rsun, and a secondary star mass and radius of 0.116 +/- 0.003 Msun and 0.155 +/- 0.003 Rsun. The mass and radius of the white dwarf in GK Vir are consistent with evolutionary models for a 50,000K carbon-oxygen core white dwarf. Although the mass and radius of the white dwarf in SDSS J1212-0123 are consistent with carbon-oxygen core models, evolutionary models imply that a white dwarf with such a low mass and in a short period binary must have a helium core. The mass and radius measurements are consistent with helium core models but only if the white dwarf has a very thin hydrogen envelope, which has not been predicted by evolutionary models. The mass and radius of the secondary star in GK Vir are consistent with evolutionary models after correcting for the effects of irradiation by the white dwarf. The secondary star in SDSS J1212-0123 has a radius ~9 per cent larger than predicted.Comment: 21 pages, 14 Figures and 11 Tables. Accepted for publication in MNRA

Stellar Coronal and Wind Models: Impact on Exoplanets

Surface magnetism is believed to be the main driver of coronal heating and stellar wind acceleration. Coronae are believed to be formed by plasma confined in closed magnetic coronal loops of the stars, with winds mainly originating in open magnetic field line regions. In this Chapter, we review some basic properties of stellar coronae and winds and present some existing models. In the last part of this Chapter, we discuss the effects of coronal winds on exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief: Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer Reference Work

The Kuiper Belt and Other Debris Disks

We discuss the current knowledge of the Solar system, focusing on bodies in the outer regions, on the information they provide concerning Solar system formation, and on the possible relationships that may exist between our system and the debris disks of other stars. Beyond the domains of the Terrestrial and giant planets, the comets in the Kuiper belt and the Oort cloud preserve some of our most pristine materials. The Kuiper belt, in particular, is a collisional dust source and a scientific bridge to the dusty "debris disks" observed around many nearby main-sequence stars. Study of the Solar system provides a level of detail that we cannot discern in the distant disks while observations of the disks may help to set the Solar system in proper context.Comment: 50 pages, 25 Figures. To appear in conference proceedings book "Astrophysics in the Next Decade

Eclipsing post-common envelope binaries from the Catalina surveys

We analyse the Catalina Real-time Transient Survey light curves of 835 spectroscopically confirmed white dwarf plus main-sequence binaries from the Sloan Digital Sky Survey (SDSS) with g < 19, in search of new eclipsing systems. We identify 29 eclipsing systems, 12 of which were previously unknown. This brings the total number of eclipsing white dwarf plus main-sequence binaries to 49. Our set of new eclipsing systems contains two with periods of 1.9 and 2.3 d, making them the longest period eclipsing white dwarf binaries known. We also identify one system which shows very large ellipsoidal modulation (almost 0.3 mag), implying that the system is both very close to Roche lobe overflow and at high inclination. However, our follow-up photometry failed to firmly detect an eclipse, meaning that either this system contains a cool white dwarf and hence the eclipse is very shallow and undetectable in our red-sensitive photometry or that it is non-eclipsing. Radial velocity measurements for the main-sequence stars in three of our newly identified eclipsing systems imply that their white dwarf masses are lower than those inferred from modelling their SDSS spectra. 13 non-eclipsing post-common envelope binaries were also identified, from either reflection or ellipsoidal modulation effects. The white dwarfs in our newly discovered eclipsing systems span a wide range of parameters, including low-mass (∼0.3 M_⊙), very hot (80 000 K) and a DC white dwarf. The spectral types of the main-sequence stars range from M2 to M6. This makes our sample ideal for testing white dwarf and low-mass star mass–radius relationships as well as close binary evolution

Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response

Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders

Targeting the IL-6 Dependent Phenotype Can Identify Novel Therapies for Cholangiocarcinoma

The need for new therapies for cholangiocarcinoma is highlighted by their poor prognosis and refractoriness to chemotherapy. Increased production of Interleukin-6 promotes cholangiocarcinoma growth and contributes to chemoresistance by activating cell survival mechanisms. We sought to identify biologically active compounds capable of ameliorating the phenotypic effects of IL-6 expression and to explore their potential therapeutic use for cholangiocarcinoma.A genomic signature associated with Interleukin-6 expression in Mz-ChA-1 human malignant cholangiocytes was derived. Computational bioinformatics analysis was performed to identify compounds that induced inverse gene changes to the signature. The effect of these compounds on cholangiocarcinoma growth was then experimentally verified in vitro and in vivo. Interactions with other therapeutic agents were evaluated using median effects analysis.A group of structurally related compounds, nitrendipine, nifedipine and felodipine was identified. All three compounds were cytotoxic to Mz-ChA-1 cells with an IC50 for felodipine of 26 µM, nitrendipine, 44 µM and nifedipine, 15 µM. Similar results were observed in KMCH-1, CC-LP-1 and TFK-1 cholangiocarcinoma cell lines. At a fractional effect of 0.5, all three agents were synergistic with either camptothecin or gemcitabine in Mz-ChA-1 cells in vitro. Co-administration of felodipine and gemcitabine decreased the growth of Mz-ChA-1 cell xenografts in nude athymic mice.Computational bioinformatics analysis of phenotype-based genomic expression can be used to identify therapeutic agents. Using this drug discovery approach based on targeting a defined tumor associated phenotype, we identified compounds with the potential for therapeutic use in cholangiocarcinoma