LATTES: a novel detector concept for a gamma-ray experiment in the Southern hemisphere

The Large Array Telescope for Tracking Energetic Sources (LATTES), is a novel concept for an array of hybrid EAS array detectors, composed of a Resistive Plate Counter array coupled to a Water Cherenkov Detector, planned to cover gamma rays from less than 100 GeV up to 100 TeVs. This experiment, to be installed at high altitude in South America, could cover the existing gap in sensitivity between satellite and ground arrays. The low energy threshold, large duty cycle and wide field of view of LATTES makes it a powerful tool to detect transient phenomena and perform long term observations of variable sources. Moreover, given its characteristics, it would be fully complementary to the planned Cherenkov Telescope Array (CTA) as it would be able to issue alerts. In this talk, a description of its main features and capabilities, as well as results on its expected performance, and sensitivity, will be presented

The Air Microwave Yield (AMY) experiment - A laboratory measurement of the microwave emission from extensive air showers

The AMY experiment aims to measure the microwave bremsstrahlung radiation (MBR) emitted by air-showers secondary electrons accelerating in collisions with neutral molecules of the atmosphere. The measurements are performed using a beam of 510 MeV electrons at the Beam Test Facility (BTF) of Frascati INFN National Laboratories. The goal of the AMY experiment is to measure in laboratory conditions the yield and the spectrum of the GHz emission in the frequency range between 1 and 20 GHz. The final purpose is to characterise the process to be used in a next generation detectors of ultra-high energy cosmic rays. A description of the experimental setup and the first results are presented.Comment: 3 pages -- EPS-HEP'13 European Physical Society Conference on High Energy Physics (July, 18-24, 2013) at Stockholm, Swede

Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. In OA, chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favouring disease progression. Similar to other wound-healing disorders, chondrocytes from OA patients show a chronic increase in the gap junction channel protein connexin43 (Cx43), which regulates signal transduction through the exchange of elements or recruitment/release of signalling factors. Although immature or stem-like cells are present in cartilage from OA patients, their origin and role in disease progression are unknown. In this study, we found that Cx43 acts as a positive regulator of chondrocyte-mesenchymal transition. Overactive Cx43 largely maintains the immature phenotype by increasing nuclear translocation of Twist-1 and tissue remodelling and proinflammatory agents, such as MMPs and IL-1β, which in turn cause cellular senescence through upregulation of p53, p16INK4a and NF-κB, contributing to the senescence-associated secretory phenotype (SASP). Downregulation of either Cx43 by CRISPR/Cas9 or Cx43-mediated gap junctional intercellular communication (GJIC) by carbenoxolone treatment triggered rediferentiation of osteoarthritic chondrocytes into a more differentiated state, associated with decreased synthesis of MMPs and proinflammatory factors, and reduced senescence. We have identified causal Cx43- sensitive circuit in chondrocytes that regulates dedifferentiation, redifferentiation and senescence. We propose that chondrocytes undergo chondrocyte-mesenchymal transition where increased Cx43-mediated GJIC during OA facilitates Twist-1 nuclear translocation as a novel mechanism involved in OA progression. These findings support the use of Cx43 as an appropriate therapeutic target to halt OA progression and to promote cartilage regeneration.This work was supported in part through funding from the Spanish Society for Rheumatology (SER; FER 2013) and Spanish Foundation for Research on Bone and Mineral Metabolism (FEIOMM), grant PRECIPITA-2015-000139 from the FECYT-Ministry of Economy and Competitiveness (to M.D.M.), grant PI16/00035 from the Health Institute ‘Carlos III’ (ISCIII, Spain), the European Regional Development Fund, ‘A way of making Europe’ from the European Union (to M.D.M.) and a grant from Xunta de Galicia IN607B 2017/21 (to M.D.M.) and pre-doctoral fellowship to M.V.-E. T.A. acknowledges support from Instituto de Salud Carlos III grants PI16/00772 and CPII16/00042, co-financed by the European Regional Development Fund (ERDF)S

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis : Fundamentals Of Care for UveitiS (FOCUS) Initiative

Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

Recovery of Meteorological Data for the Observatory of A Guarda, Spain

We herein describe the recovery of a series of data on temperature, humidity, precipitation, evaporation, wind, and local weather conditions from documentary sources obtained from the Jesuit observatory of A Guarda (Galicia, Spain) for the period 1881–1896. The data were digitized and made available in accessible electronic formats. Comparisons were made with present-day meteorological data obtained from two nearby stations. We further believe that the discovery of some new complementary documentary sources made during the present research could be a basis for future data recovery efforts. Among these new results, early ozone data from the period are of outstanding importance to meteorologists

New insights into the genetic component of non-infectious uveitis through an Immunochip strategy

Background: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. Methods: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. Results: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. Conclusions: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition

Litterfall, litter decomposition and associated nutrient fluxes in Pinus halepensis: influence of tree removal intensity in a Mediterranean forest

The online version of this article (doi:10.1007/s10342-015-0893-z) contains supplementary material, which is available to authorized users[EN] Our knowledge about the influence of silvicultural treatments on nutrient cycling processes in Mediterranean forests is still limited. Four levels of tree removal were compared in an Aleppo pine forest in eastern Spain to determine the effects on litterfall, litter decomposition and the associated nutrient fluxes after 12 years. Removal treatments included clearfelling, two shelterwood intensities (60 and 75 % of basal area removed) and untreated controls. Twelve years later, the basal area removed still explained 60 % of litterfall mass variance and 60 % of C, 52 % of N, 45 % of P, 17 % of K, 47 % of Ca and 60 % of Mg return variances. Litter decomposed somewhat more slowly in clearfellings compared to controls (p = 0.049), accumulated more Ca and released less K compared to the other three treatments. This was explained by contamination with mineral particles due to the poorly developed O horizon in clearfellings. We conclude that the management practices reduced the nutrient return via litterfall, but the nutrient release through decomposition seems poorly sensitive to canopy disturbance. In order to accurately quantify the harvesting impacts on nutrient cycling in this Mediterranean forest system, it is necessary to measure the litterfall of the understory layer.This work has been supported by a fellowship from the Generalitat Valenciana, Conselleria de Educacion, Formacion y Empleo awarded to L. Lado-Monserrat (BFPI/2008/041). Silvicultural treatments were carried out by the Mediterranean Centre for Environmental Studies (CEAM) through programme "I + D en relacion con la restauracion de la cubierta vegetal y otros aspectos de investigacion forestal". Dataloggers and probes were provided by the Generalitat Valenciana through Project "Efecto de diferentes sistemas de aclareo de masa forestal sobre la disponibilidad de agua, nutrientes y la regeneracion de la masa arborea y arbustiva en parcelas de pinar" (GV06/126). We acknowledge Joana Oliver, Ruth M. Tavera and Daniel Fortanet for their help in the laboratory and in the field. The authors wish to thank Francisco Galiana for his assistance, including help in fieldwork and providing information about the experimental design of the silvicultural treatments. Thanks also go to Rafael Herrera from the Centro de Ecologia, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela and two anonymous reviewers for critically reviewing the manuscript.Lado Monserrat, L.; Lidón, A.; Bautista, I. (2015). Litterfall, litter decomposition and associated nutrient fluxes in Pinus halepensis: influence of tree removal intensity in a Mediterranean forest. 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Lack of replication of interactions between polymorphisms in rheumatoid arthritis susceptibility: case-control study

Introduction: Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) × protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti-cyclic citrullinated peptide-positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies. Methods: A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described. Results: Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term the originally reported finding or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods. Conclusions: None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists