The enormous outer Galaxy HII region CTB 102

We present new radio recombination line observations of the previously unstudied HII region CTB 102. Line parameters are extracted and physical parameters describing the gas are calculated. We estimate the distance to CTB 102 to be 4.3 kpc. Through comparisons with HI and 1.42 GHz radio continuum data, we estimate the size of CTB 102 to be 100-130 pc, making it one of the largest HII regions known, comparable to the W4 complex. A stellar wind blown bubble model is presented as the best explanation for the observed morphology, size and velocities.Comment: 26 pages, 8 figures. Accepted for publication by The Astrophysical Journa

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia; Sudden cardiac death; Ventricular arrhythmiasTaquicardia ventricular polimórfica catecolaminérgica; Muerte cardíaca súbita; Arritmias ventricularesTaquicàrdia ventricular polimòrfica catecolaminèrgica; Mort cardíaca sobtada; Arítmies ventricularsBACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14–29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7–3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4–7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0–6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38–0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31–0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14–0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.A.A.W. was funded by Predict-2, EU E-rare grant (Transnational Research Projects on Rare Diseases 2015, Improving CPVT). S.S. was funded by the Heart and Stroke Foundation (grant G-19-0024239). M.J.A. was supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. A.L. was funded by a grant from Programme Hospitalier de Recherche Clinique–PHRC 2014 (Ministère de la Santé N° AOR 04070). C.S. is the recipient of a National Health and Medical Research Council Practitioner Fellowship (No.1154992) and was supported by a New South Wales Health Cardiovascular Disease Clinician Scientist Grant. S.O. was funded by AMED (JP18ek0109202] and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (15K09689). J.T.H. was funded by the John and Birthe Meyer Family Foundation. K.H.H. was funded by the Norwegian Research Council (ProCardio No.309762, GENE POSITIVE No. 288438, and EMPATHY No. 298736). E.Z. was funded by Mécanismes Proarythmiques Dépendant du Sodium et du Calcium, Agènce Nationale de la Recherche (ANR-19-CE14-0031-001)

Radio polarimetric imaging of the interstellar medium: magnetic field and diffuse ionized gas structure near the W3/W4/W5/HB3 complex

We have used polarimetric imaging to study the magneto-ionic medium of the Galaxy, obtaining 1420 MHz images with an angular resolution of 1' over more than 40 square-degrees of sky around the W3/W4/W5/HB3 HII region/SNR complex in the Perseus Arm. Features detected in polarization angle are imposed on the linearly polarized Galactic synchrotron background emission by Faraday rotation arising in foreground ionized gas having an emission measure as low as 1 cm^{-6} pc. Several new remarkable phenomena have been identified, including: mottled polarization arising from random fluctuations in a magneto-ionic screen that we identify with a medium in the Perseus Arm, probably in the vicinity of the HII regions themselves; depolarization arising from very high rotation measures (several times 10^3 rad m^{-2}) and rotation measure gradients due to the dense, turbulent environs of the HII regions; highly ordered features spanning up to several degrees; and an extended influence of the HII regions beyond the boundaries defined by earlier observations. In particular, the effects of an extended, low-density ionized halo around the HII region W4 are evident, probably an example of the extended HII envelopes postulated as the origin of weak recombination-line emission detected from the Galactic ridge. Our polarization observations can be understood if the uniform magnetic field component in this envelope scales with the square-root of electron density and is 20 microG at the edge of the depolarized region around W4, although this is probably an over-estimate since the random field component will have a significant effect.Comment: 18 pages, 8 figures (7 jpeg and 1 postscript), accepted for publication in the Astrophysical Journa

A Decreased Frequency of Regulatory T Cells in Patients with Common Variable Immunodeficiency

Introduction: Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4(+)CD25(high) regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens.Objective: in this study we set out to investigate the frequency of Treg cells in CVID patients and correlate with their immune activation status.Materials and Methods: Sixteen patients (6 males and 10 females) with CVID who had been treated with regular intravenous immunoglobulin and 14 controls were enrolled. Quantitative analyses of peripheral blood mononuclear cells (PBMC) were performed by multiparametric flow cytometry using the following cell markers: CD38, HLA-DR, CCR5 ( immune activation); CD4, CD25, FOXP3, CD127, and OX40 (Treg cells); Ki-67 and IFN-gamma (intracellular cytokine).Results: A significantly lower proportion of CD4(+)CD25(high) FOXP3 T cells was observed in CVID patients compared with healthy controls (P<0.05). in addition to a higher proportion of CD8(+) T cells from CVID patients expressing the activation markers, CD38(+) and HLA-DR(+) (P<0.05), we observed no significant correlation between Tregs and immune activation.Conclusion: Our results demonstrate that a reduction in Treg cells could have impaired immune function in CVID patients.Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Priming Immunization with DNA Augments Immunogenicity of Recombinant Adenoviral Vectors for Both HIV-1 Specific Antibody and T-Cell Responses

Induction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies.The first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination.rAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8(+) T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4(+) and CD8(+) T-cells expressed multiple functions and were predominantly long-term (CD127(+)) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition.Heterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses.ClinicalTrials.gov NCT00102089, NCT00108654

Detection of Extended VHE Gamma Ray Emission from G106.3+2.7 with VERITAS

We report the detection of very-high-energy (VHE) gamma-ray emission from supernova remnant (SNR) G106.3+2.7. Observations performed in 2008 with the VERITAS atmospheric Cherenkov gamma-ray telescope resolve extended emission overlapping the elongated radio SNR. The 7.3 sigma (pre-trials) detection has a full angular extent of roughly 0.6deg by 0.4deg. Most notably, the centroid of the VHE emission is centered near the peak of the coincident 12CO (J = 1-0) emission, 0.4deg away from the pulsar PSR J2229+6114, situated at the northern end of the SNR. Evidently the current-epoch particles from the pulsar wind nebula are not participating in the gamma-ray production. The VHE energy spectrum measured with VERITAS is well characterized by a power law dN/dE = N_0(E/3 TeV)^{-G} with a differential index of G = 2.29 +/- 0.33stat +/- 0.30sys and a flux of N_0 = (1.15 +/- 0.27stat +/- 0.35sys)x 10^{-13} cm^{-2} s^{-1} TeV^{-1}. The integral flux above 1 TeV corresponds to ~5 percent of the steady Crab Nebula emission above the same energy. We describe the observations and analysis of the object and briefly discuss the implications of the detection in a multiwavelength context.Comment: 5 pages, 2 figure

The HII Region KR 140: Spontaneous Formation of a High Mass Star

We have used a multiwavelength data set from the Canadian Galactic Plane Survey (CGPS) to study the Galactic HII region KR 140, both on the scale of the nebula itself and in the context of the star forming activity in the nearby W3/W4/W5 complex of molecular clouds and HII regions. From both radio and infrared data we have found a covering factor of about 0.5 for KR 140 and we interpret the nebula as a bowl-shaped region viewed close to face on. Extinction measurements place the region on the near side of its parent molecular cloud. The nebula is kept ionized by one O8.5 V(e) star, VES 735, which is less than a few million years old. CO data show that VES 735 has disrupted much of the original molecular cloud for which the estimated mass and density are about 5000 $M_{\odot}$ and 100 cm$^{-3}$, respectively. KR 140 is isolated from the nearest star forming activity, in W3. Our data suggest that KR 140 is an example of spontaneous (i.e., non-triggered) formation of, unusually, a high mass star.Comment: 46 pages; includes 15 figures; accepted by the Ap

Suppression of xylan endotransglycosylase PtxtXyn10A affects cellulose microfibril angle in secondary wall in aspen wood.

Certain xylanases from family GH10 are highly expressed during secondary wall deposition, but their function is unknown. We carried out functional analyses of the secondary-wall specific PtxtXyn10A in hybrid aspen (Populus tremula × tremuloides). PtxtXyn10A function was analysed by expression studies, overexpression in Arabidopsis protoplasts and by downregulation in aspen. PtxtXyn10A overexpression in Arabidopsis protoplasts resulted in increased xylan endotransglycosylation rather than hydrolysis. In aspen, the enzyme was found to be proteolytically processed to a 68 kDa peptide and residing in cell walls. Its downregulation resulted in a corresponding decrease in xylan endotransglycosylase activity and no change in xylanase activity. This did not alter xylan molecular weight or its branching pattern but affected the cellulose-microfibril angle in wood fibres, increased primary growth (stem elongation, leaf formation and enlargement) and reduced the tendency to form tension wood. Transcriptomes of transgenic plants showed downregulation of tension wood related genes and changes in stress-responsive genes. The data indicate that PtxtXyn10A acts as a xylan endotransglycosylase and its main function is to release tensional stresses arising during secondary wall deposition. Furthermore, they suggest that regulation of stresses in secondary walls plays a vital role in plant development.Formas (including HemiPop and FuncFiber), Swedish Research Council (VR), Swedish Governmental Agency for Innovation Systems (VINNOVA), Swedish Center for Biomimetic Fiber Engineering (funded by the Knut & Alice Wallenberg Foundation and the Foundation for Strategic Research), European projects EDEN (QLK5-CT-2001-00443) and RENEWALL, FORE, Bio4Energy, Wood Ultrastructure Research Centre, SamNordisk Skogsforskning (project no. 107), Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 24580243) and the Academy of Finland (1127759).This is the accepted manuscript. The final version is available at http://onlinelibrary.wiley.com/doi/10.1111/nph.13099/abstract

CD8+ T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation

Background. It is generally accepted that CD8(+) T cell responses play an important role in control of immunodeficiency virus replication. the association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8(+) cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8(+) cells, implicating that these cells actively suppress viral replication in ECs. Methods and Findings. Here we show that three ECs in that study made at least seven robust CD8(+) T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8(+) T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. Conclusions. Together, our data suggest that Mamu-B*08-restricted CD8(+) T cell responses effectively control replication of pathogenic SIV(mac)239. All seven regions encoding Mamu-B*08-restricted CD8(+) T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8(+) T cell responses. SIVmac239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8(+) T cell-mediated control of HIV replication in humans.National Institutes of Health (NIH)National Center for Research Resources (NCRR)Japan Health Sciences FoundationKent State University Research CouncilOhio Board of Regents Research ChallengeResearch Facilities ImprovementUniv Wisconsin, WNPRC, Madison, WI 53706 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniv Wisconsin, Dept Pathol & Lab Med, Madison, WI USALa Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USAUniv Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, EnglandKent State Univ, Dept Biol Sci, Kent, OH 44242 USAUniv S Carolina, Dept Biol Sci, Columbia, SC 29208 USAUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilNational Institutes of Health (NIH): HHSN266200400088CNational Institutes of Health (NIH): R01 AI049120National Institutes of Health (NIH): R01 AI052056National Institutes of Health (NIH): R24 RR015371National Institutes of Health (NIH): R24 RR016038National Institutes of Health (NIH): R21 AI068586National Center for Research Resources (NCRR): P51 RR000167Japan Health Sciences Foundation: GM43940Research Facilities Improvement: RR15459-01Research Facilities Improvement: RR020141-01Web of Scienc