The protoMIRAX Hard X-ray Imaging Balloon Experiment

The protoMIRAX hard X-ray imaging telescope is a balloon-borne experiment developed as a pathfinder for the MIRAX satellite mission. The experiment consists essentially in a coded-aperture hard X-ray (30-200 keV) imager with a square array (13$\times$13) of 2mm-thick planar CZT detectors with a total area of 169 cm$^2$. The total, fully-coded field-of-view is $21^{\circ}\times 21^{\circ}$ and the angular resolution is 1$^{\circ}$43'. In this paper we describe the protoMIRAX instrument and all the subsystems of its balloon gondola, and we show simulated results of the instrument performance. The main objective of protoMIRAX is to carry out imaging spectroscopy of selected bright sources to demonstrate the performance of a prototype of the MIRAX hard X-ray imager. Detailed background and imaging simulations have been performed for protoMIRAX balloon flights. The 3$\sigma$ sensitivity for the 30-200 keV range is ~1.9 $\times$ 10$^{-5}$ photons cm$^{-2}$ s$^{-1}$ for an integration time of 8 hs at an atmospheric depth of 2.7 g cm$^{-2}$ and an average zenith angle of 30$^{\circ}$. We have developed an attitude control system for the balloon gondola and new data handling and ground systems that also include prototypes for the MIRAX satellite. We present the results of Monte Carlo simulations of the camera response at balloon altitudes, showing the expected background level and the detailed sensitivity of protoMIRAX. We also present the results of imaging simulations of the Crab region. The results show that protoMIRAX is capable of making spectral and imaging observations of bright hard X-ray source fields. Furthermore, the balloon observations will carry out very important tests and demonstrations of MIRAX hardware and software in a near space environment.Comment: 9 pages, 13 figures, accepted for publication in Astronomy & Astrophysic

Polymorphisms in IL12A and cockroach allergy in children with asthma

<p>Abstract</p> <p>Background</p> <p>IL12A has been implicated in T-cell development and may thus influence the development of atopy and allergic diseases.</p> <p>Methods</p> <p>We tested for association between four linkage disequilibrium (LD)-tagging SNPs (rs2243123, rs2243151, rs668998, and rs17826053) in <it>IL12A </it>and asthma and allergy-related (serum total and allergen-specific IgE, and skin test reactivity [STR] to two common allergens) phenotypes in two samples: 417 Costa Rican children with asthma and their parents, and 470 families of 503 white children in the Childhood Asthma Management Program (CAMP). The analysis was conducted using the family-based association test (FBAT) statistic implemented in the PBAT program.</p> <p>Results</p> <p>Among Costa Rican children with asthma, homozygosity for the minor allele of each of two SNPs in <it>IL12A </it>(rs2243123 and rs2243151) was associated with increased risks of STR to American cockroach (P ≤ 0.03 for both SNPs), STR to German cockroach (P ≤ 0.01 for both SNPs), and having a positive IgE to German cockroach (P < 0.05 for both SNPs). Among children in CAMP, homozygosity for the minor allele of SNP rs2243151 in <it>IL12A </it>was inversely associated with STR to German cockroach (P = 0.03) and homozygosity for the minor allele of SNP rs17826053 in <it>IL12A </it>was associated with increased risks of STR to American cockroach (P = 0.01) and STR to German cockroach (P = 0.007). There was no significant association between any SNP in <it>IL12A </it>and asthma, STR to dust mite, or total IgE in Costa Rica or CAMP.</p> <p>Conclusion</p> <p>Our findings suggest that variants in <it>IL12A </it>influence cockroach allergy among children with asthma.</p

Lethal iron deprivation induced by non-neutralizing antibodies targeting transferrin receptor 1 in malignant B cells

A number of antibodies have been developed that induce lethal iron deprivation (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing transferrin (Tf) binding, blocking internalization of the receptor and/or inducing its degradation. We have developed recombinant antibodies targeting human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are cytotoxic to certain malignant B-cells. We now show that internalization of TfR1 bound to these antibodies can lead to its sequestration and degradation, as well as reduced Tf uptake, and the induction of a transcriptional response consistent with iron deprivation, which is mediated in part by downstream targets of p53. Cells resistant to these antibodies do not sequester and degrade TfR1 after internalization of the antibody/receptor complex, and accordingly maintain their ability to internalize Tf. These findings are expected to facilitate the rational design and clinical use of therapeutic agents targeting iron import via TfR1 in hematopoietic malignancies.Fil: Rodríguez, José A.. University of California at Los Angeles; Estados UnidosFil: Luria Pérez, Rosendo. University of California at Los Angeles; Estados Unidos. Hospital infantil de México “Federico Gómez”; MéxicoFil: López Valdés, Héctor E.. University of California at Los Angeles; Estados UnidosFil: Casero, David. University of California at Los Angeles; Estados UnidosFil: Daniels, Tracy R.. University of California at Los Angeles; Estados UnidosFil: Patel, Shabnum. University of California at Los Angeles; Estados UnidosFil: Avila, David. University of California at Los Angeles; Estados UnidosFil: Leuchter, Richard. University of California at Los Angeles; Estados UnidosFil: So, Sokuntheavy. University of California at Los Angeles; Estados UnidosFil: Ortiz Sánchez, Elizabeth. University of California at Los Angeles; Estados UnidosFil: Bonavida, Benjamin. University of California at Los Angeles; Estados UnidosFil: Martínez Maza, Otoniel. University of California at Los Angeles; Estados UnidosFil: Charles, Andrew C.. University of California at Los Angeles; Estados UnidosFil: Pellegrini, Matteo. University of California at Los Angeles; Estados UnidosFil: Helguera, Gustavo Fernando. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Penichet, Manuel L.. University of California at Los Angeles; Estados Unido

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Combined fit of spectrum and composition data as measured by the Pierre Auger Observatory

We present a combined fit of a simple astrophysical model of UHECR sources to both the energy spectrum and mass composition data measured by the Pierre Auger Observatory. The fit has been performed for energies above 5⋅1018 eV, i.e.~the region of the all-particle spectrum above the so-called "ankle" feature. The astrophysical model we adopted consists of identical sources uniformly distributed in a comoving volume, where nuclei are accelerated through a rigidity-dependent mechanism. The fit results suggest sources characterized by relatively low maximum injection energies, hard spectra and heavy chemical composition. We also show that uncertainties about physical quantities relevant to UHECR propagation and shower development have a non-negligible impact on the fit results.Fil: Aab, A.. Radboud Universiteit Nijmegen; Países BajosFil: Abreu, P.. Universidade de Lisboa; PortugalFil: Aglietta, M.. Istituto Nazionale di Astrofisica; ItaliaFil: Al Samarai, I.. Universite de Paris VI. Institut des Nanosciences de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Albuquerque, I. F. M.. Universidade de Sao Paulo; BrasilFil: Allekotte, Ingomar. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Almela, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Alvarez Castillo, J.. Universidad Nacional Autónoma de México; MéxicoFil: Alvarez Muñiz, J.. Universidad de Santiago de Compostela; EspañaFil: Anastasi, G. A.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Anchordoqui, Luis A.. City University of New York; Estados UnidosFil: Andrada, Betiana Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Andringa, S.. Universidade Nova de Lisboa; PortugalFil: Aramo, C.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Arqueros, F.. Universidad Complutense de Madrid; EspañaFil: Arsene, N.. University of Bucharest; RumaniaFil: Asorey, Hernán Gonzalo. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Universidad Industrial de Santander; ColombiaFil: Assis, P.. Universidade de Lisboa; PortugalFil: Aublin, J.. Université Paris 6; Francia. Université Paris 7; Francia. Centre National de la Recherche Scientifique; FranciaFil: Avila, G.. Observatorio Pierre Auger; ArgentinaFil: Badescu, A. M.. Observatorio Pierre Auger; ArgentinaFil: Balaceanu, A.. “Horia Hulubei” National Institute for Physics and Nuclear Engineering; RumaniaFil: Luz Barreira, R. J.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Beatty, J. J.. Ohio State University; Estados UnidosFil: Figueira, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Platino, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Wundheiler, Brian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Wahlberg, Hernan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Mollerach, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Biermann, P. L.. Max-Planck-Institut f¨ur Radioastronomie; Alemani

Regulation of mammalian liver methionine adenosyltransferase

S-adenosylmethionine (SAM) is an essential metabolite in all cells. SAM is the most important biological methyl group donor and is a precursor in the synthesis of polyamines. Methionine adenosyltransferase (MAT; EC 2.5.1.6) catalyzes the only known SAM biosynthetic reaction from methionine and ATP. In mammalian tissues, three different forms of MAT (MAT I, MAT III and MAT II) have been identified that are the product of two different genes (MAT1A and MAT2A). Although MAT2A is expressed in all mammalian tissues, the expression of MAT1A is primarily restricted to adult liver. In mammals, up to 85% of all methylation reactions and as much as 48% of methionine metabolism occurs in the liver, which indicates the important role of this organ in the regulation of blood methionine. Recent evidence indicates that not only is SAM the main biological methyl group donor and an intermediate metabolite in methionine catabolism, but it is also an intracellular control switch that regulates essential hepatic functions such as liver regeneration and differentiation as well as the sensitivity of this organ to injury. Therefore, knowledge of factors that regulate the activity of MAT I/III, the specific liver enzyme, is essential to understand how cellular SAM levels are controlled

A genome-wide association study in Hispanics/Latinos identifies novel signals for lung function: the Hispanic Community Health Study/Study of Latinos

Rationale:: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry. Objectives: Perform a GWAS of COPD-phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations. Methods: :GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies. Measurements and Main Results: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for forced expiratory volume in one second (FEV1) in ZSWIM7 (rs4791658; p=4.99×10-9) replicated. A rare variant (MAF=0.002) in HAL (rs145174011) was associated with FEV1 to forced vital capacity (FEV1/FVC) (p=9.59×10-9) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; p=1.92×10-8) approached statistical significance for replication in admixed populations of African ancestry and a novel SNP for COPD in PDZD2 (rs7709630; p=1.56×10-8) regionally replicated. Additionally, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in HCHS/SOL at the genome-wide significance level. Conclusions: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing togenetic etiologies of COPD

Updating the Food-Based Dietary Guidelines for the Spanish Population: The Spanish Society of Community Nutrition (SENC) Proposal

Diet-related risk factors and physical inactivity are among the leading risk factors for disability and are responsible for a large proportion of the burden of chronic non-communicable diseases. Food-based dietary guidelines (FBDGs) are useful tools for nutrition policies and public health strategies to promote healthier eating and physical activity. In this paper, we discuss the process followed in developing the dietary guidelines for the Spanish population by the Spanish Society of Community Nutrition (SENC) and further explain the collaboration with primary healthcare practitioners as presented in the context of the NUTRIMAD 2018 international congress of SENC. From a health in all policies approach, SENC convened a group of experts in nutrition and public health to review the evidence on diet-health, nutrient intake and food consumption in the Spanish population, as well as food preparation, determinants and impact of diet on environmental sustainability. The collaborative group drafted the document and designed the graphic icon, which was then subject to a consultation process, discussion, and qualitative evaluation. Next, a collaborative group was established to plan a dissemination strategy, involving delegates from all the primary healthcare scientific societies in Spain. A product of this collaboration was the release of an attractive, easy-to-understand publication

Asthma-susceptibility variants identified using probands in case-control and family-based analyses

<p>Abstract</p> <p>Background</p> <p>Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs.</p> <p>Methods</p> <p>We used probands from the Childhood Asthma Management Program (CAMP) in two primary genome-wide association study designs: (1) probands were combined with publicly available population controls in a case-control design, and (2) probands and their parents were used in a family-based design. We followed a two-stage replication process utilizing three independent populations to validate our primary findings.</p> <p>Results</p> <p>We found that single nucleotide polymorphisms with similar case-control and family-based association results were more likely to replicate in the independent populations, than those with the smallest p-values in either the case-control or family-based design alone. The single nucleotide polymorphism that showed the strongest evidence for association to asthma was rs17572584, which replicated in 2/3 independent populations with an overall p-value among replication populations of 3.5E-05. This variant is near a gene that encodes an enzyme that has been implicated to act coordinately with modulators of Th2 cell differentiation and is expressed in human lung.</p> <p>Conclusions</p> <p>Our results suggest that using probands from family-based studies in case-control designs, and combining results of both family-based and case-control approaches, may be a way to augment our ability to find SNPs associated with asthma and other complex diseases.</p