Synthesis of optimal digital shapers with arbitrary noise using a genetic algorithm

This paper presents structure, design and implementation of a novel technique for determining the optimal shaping, in time-domain, for spectrometers by means of a Genetic Algorithm (GA) specifically designed for this purpose. The proposed algorithm is able to adjust automatically the coefficients for shaping an input signal. Results of this experiment have been compared to a previous simulated annealingalgorithm. Finally, its performance and capabilities were tested using simulation data and a real particle detector, as a scintillator.Ministerio de Ciencia e Innovació

eIMRT: a web platform for the verification and optimization of radiation treatment plans

The eIMRT platform is a remote distributed computing tool that provides users with Internet access to three different services: Monte Carlo optimization of treatment plans, CRT & IMRT treatment optimization, and a database of relevant radiation treatments/clinical cases. These services are accessible through a user-friendly and platform independent web page. Its flexible and scalable design focuses on providing the final users with services rather than a collection of software pieces. All input and output data (CT, contours, treatment plans and dose distributions) are handled using the DICOM format. The design, implementation, and support of the verification and optimization algorithms are hidden to the user. This allows a unified, robust handling of the software and hardware that enables these computation-intensive services. The eIMRT platform is currently hosted by the Galician Supercomputing Center (CESGA) and may be accessible upon request (there is a demo version at http://eimrt.cesga.es:8080/ eIMRT2/demo; request access in http://eimrt.cesga.es/signup.html). This paper describes all aspects of the eIMRT algorithms in depth, its user interface, and its services. Due to the flexible design of the platform, it has numerous applications including the intercenter comparison of treatment planning, the quality assurance of radiation treatments, the design and implementation of new approaches to certain types of treatments, and the sharing of information on radiation treatment techniques. In addition, the web platform and software tools developed for treatment verification and optimization have a modular design that allows the user to extend them with new algorithms. This software is not a commercial product. It is the result of the collaborative effort of different public research institutions and is planned to be distributed as an open source project. In this way, it will be available to any user; new releases will be generated with the new implemented codes or upgradesThis work was financed by Xunta de Galicia of Spain through grant PGIDT05SIN00101CT and by the European Community through the BeInGrid projectS

An 8-mm diameter fibre robot positioner for massive spectroscopy surveys

This article has been accepted for publication in Monthly Notices of Royal Astronomical Society © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reservedMassive spectroscopic survey are becoming trendy in astrophysics and cosmology, as they can address new fundamental knowledge such as understanding the formation of the Milky Way and probing the nature of the mysterious dark energy. To enable massive spectroscopic surveys, new technology has been developed to place thousands of optical fibres at a given position on a focal plane. This technology needs to be: (1) accurate, with micrometer positional accuracy; (2) fast to minimize overhead; (3) robust to minimize failure; and (4) low cost. In this paper, we present the development, properties, and performance of a new single 8-mm in diameter fibre positioner robot, using two 4-mm DC-brushless gearmotors, that allows us to achieve accuracies up to 0.07 arcsec (5 μm). This device has been developed in the context of the Dark Energy Spectroscopic InstrumentWe acknowledge support from the Spanish MICINNs Consolider-Ingenio 2010 Program me under grant MultiDark CSD2009-00064, HEPHACOS S2009/ESP-1473, and MINECO Centro de Excelencia Severo Ochoa Programme under grant SEV-2012-0249. We also thank the support from a CSIC-AVS contract through MICINN grant AYA2010-21231-C02- 01, and CDTI grant IDC-20101033; and support from the Spanish MINECO research grants AYA2012-31101 and FPA2012-34694. JPK, PH and LM acknowledge support from the ERC advanced grant LIDA and from an SNF Interdisciplinary grant

An 8-mm diameter fibre robot positioner for massive spectroscopy surveys

Massive spectroscopic survey are becoming trendy in astrophysics and cosmology, as they can address new fundamental knowledge such as understanding the formation of the Milky Way and probing the nature of the mysterious dark energy. To enable massive spectroscopic surveys, new technology has been developed to place thousands of optical fibres at a given position on a focal plane. This technology needs to be: (1) accurate, with micrometer positional accuracy; (2) fast to minimize overhead; (3) robust to minimize failure; and (4) low cost. In this paper, we present the development, properties, and performance of a new single 8-mm in diameter fibre positioner robot, using two 4-mm DC-brushless gearmotors, that allows us to achieve accuracies up to 0.07arcsec (5 μm). This device has been developed in the context of the Dark Energy Spectroscopic Instrument.

Factores de riesgo para trastornos de la alimentación en los alumnos de la Universidad de Manizales

ResumenObjetivo: Determinar la frecuencia de los factores de riesgo para trastornos de la alimentación en estudiantes de la Universidad de Manizales. Materiales y métodos: De 3,610 estudiantes regulares de la Universidad  de Manizales se tomó una muestra de 165 estudiantes, quienes respondieron un cuestionario integrado compuesto por variables demográficas, las escalas de Zung para ansiedad o depresión,el Eating Disorderrs Inventory (EDI2) y el Apgar familiar; además se tomaron las medidas de peso, talla, índice de masa corporal y pliegue en el antebrazo. Resultado: Un12.7% de la población presentó factor de riesgo positivo para trastornos de la conducta alimentaría, 17.3% de la población femenina y el 3.8% de la población masculina; las personas con mayor factor de riesgo fueron las mujeres en la facultad de Comunicación Social y Periodismo (24.1%). Se determinó una  relación significativa entre la variable impulso por la delgadez con la ansiedad o depresión. El mayor índice de masa corporal y de porcentaje de grasa está asociado con un aumentoen la variable impulso por la delgadez. Conclusiones:Se encontraron factores de riesgo asociados con trastornos de la alimentación. La frecuencia del factor de riesgo según EDI2 en este estudio fue más baja que la encontrada en estudios realizados en Medellín y Bogotá.[Cano AA, Castaño JJ, Corredor DA, García AM, González M, Lloreda OL, et al. Factores de riesgo para trastornos de la alimentación en los alumnos de la Universidad de Manizales. MedUNAB 2007; 10:187-194].Palabras claves: Trastornos de la conducta alimentaria, factores de riesgo; Anorexia nerviosa, Bulimia

Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols

Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well-defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox-based approaches to cancer therapyThis research was partially supported by 1) “la Caixa” Foundation, Ref. LCF/PR/PR12/11070003 to F.D. and M.A.L.Q.; 2) Ministerio de Ciencia, Innovación y Universidades (MAT2017-89678-R, AEI/FEDER, UE) to F.D. and A.V.; 3) the Consellería de Educación (Xunta de Galicia), Grants No. Grupos Ref. Comp. ED431C 2017/22, ED431C 2019/13 and AEMAT-ED431E2018/08 to M.A.L.Q.; and ED431C 2019/13 to A.V. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme (Bac-To-Fuel) under Grant Agreement No. 825999 (M.A.L.Q.). J.C.H. acknowledge financial support from European Union's Horizon 2020 research and innovation programme under grant agreement no. 823717-ESTEEM3, and the MICIIN (projects PID2019-107578GA-100 and PID-110018GA-100). J.M.D, L.J.G., and F.G.R. thank to the ANPCyT (PICT 2015-2285 and 2017-3944), UNLP (Project 11/X790) and the partial support by the Laboratório Nacional de Luz Síncrotron (LNLS, Brazil) under proposal SXS-20180280. G.B. acknowledges the CINECA Award N. IsC51, year 2017, under the ISCRA initiative, for the availability of high-performance computing resources and support. D.B. expresses gratitude for a postdoctoral grant from Xunta de Galicia, Spain (POS-A/2013/018). B.D. expresses gratitude for a predoctoral grant from MICINN, Spain (BES-2016-076765). F.D. and A.V. also acknowledged Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022 ref ED431G 2019/02) and the European Union (European Regional Development Fund – ERDF). Work in M.P.M.'s lab was supported by the Medical Research Council UK (MC_U105663142). T.G.C. gratefully acknowledges the technical assistance of María José Otero-Fraga (FIDIS)S

SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators

20 Pág.Coronaviruses (CoVs) of genera α, β, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.This work was supported by grants from the Government of Spain (BIO2016-75549-R; PID2019-107001RB-I00 AEI/FEDER, UE; SEV 2017-0712 and PIE_INTRAMURAL_LINEA 1- 202020E079), CSIC (PIE_INTRAMURAL-202020E043), the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), the European Commission (H2020-SC1- 2019, ISOLDA Project No. 848166-2), and the U.S. National Institutes of Health (NIH) (2P01AI060699). J.M.H. received a contract from Comunidad de Madrid (Y2020/BIO-6576, COVID-PREclinical-MODels-CM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. In vivo experiments were performed at INIA-CISA (Madrid, Spain)Peer reviewe

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Plant diversity patterns in neotropical dry forests and their conservation implications

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.Seasonally dry tropical forests are distributed across Latin America and the Caribbean and are highly threatened, with less than 10% of their original extent remaining in many countries. Using 835 inventories covering 4660 species of woody plants, we show marked floristic turnover among inventories and regions, which may be higher than in other neotropical biomes, such as savanna. Such high floristic turnover indicates that numerous conservation areas across many countries will be needed to protect the full diversity of tropical dry forests. Our results provide a scientific framework within which national decision-makers can contextualize the floristic significance of their dry forest at a regional and continental scale.This paper is the result of the Latin American and Caribbean Seasonally Dry Tropical Forest Floristic Network (DRYFLOR), which has been supported at the Royal Botanic Garden Edinburgh by a Leverhulme Trust International Network Grant (IN-074). This work was also supported by the U.K. Natural Environment Research Council grant NE/I028122/1; Colciencias Ph.D. scholarship 529; Synthesys Programme GBTAF-2824; the NSF (NSF 1118340 and 1118369); the Instituto Humboldt (IAvH)–Red colombiana de investigación y monitoreo en bosque seco; the Inter-American Institute for Global Change Research (IAI; Tropi-Dry, CRN2-021, funded by NSF GEO 0452325); Universidad Nacional de Rosario (UNR); and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). The data reported in this paper are available at www.dryflor.info. R.T.P. conceived the study. M.P., A.O.-F., K.B.-R., R.T.P., and J.W. designed the DRYFLOR database system. K.B.-R. and K.G.D. carried out most analyses. K.B.-R. R.T.P., and K.G.D. wrote the manuscript with substantial input from A.D.-S., R.L.-P., A.O.-F., D.P., C.Q., and R.R. All the authors contributed data, discussed further analyses, and commented on various versions of the manuscript. K.B.-R. thanks G. Galeano who introduced her to dry forest research. We thank J. L. Marcelo, I. Huamantupa, C. Reynel, S. Palacios, and A. Daza for help with fieldwork and data entry in Peru