Adsorption of hydrogen on the surface and sub-surface of Cu(111)

The interaction of atomic hydrogen with the Cu(111) surface was studied by a combined experimental-theoretical approach, using infrared reflection absorption spectroscopy, temperature programmed desorption, and density functional theory (DFT). Adsorption of atomic hydrogen at 160 K is characterized by an anti-absorption mode at 754 cm−1 and a broadband absorption in the IRRA spectra, related to adsorption of hydrogen on three-fold hollow surface sites and sub-surface sites, and the appearance of a sharp vibrational band at 1151 cm−1 at high coverage, which is also associated with hydrogen adsorption on the surface. Annealing the hydrogen covered surface up to 200 K results in the disappearance of this vibrational band. Thermal desorption is characterized by a single feature at ∼295 K, with the leading edge at ~250 K. The disappearance of the sharp Cu-H vibrational band suggests that with increasing temperature the surface hydrogen migrates to sub-surface sites prior to desorption from the surface. The presence of sub-surface hydrogen after annealing to 200 K is further demonstrated by using CO as a surface probe. Changes in the Cu-H vibration intensity are observed when cooling the adsorbed hydrogen at 180 K to 110 K, implying the migration of hydrogen. DFT calculations show that the most stable position for hydrogen adsorption on Cu(111) is on hollow surface sites, but that hydrogen can be trapped in the second sub-surface layer.Fil: Mudiyanselage, Kumudu. Brookhaven National Laboratory; Estados UnidosFil: Yang, Yixiong. State University Of New York; Estados UnidosFil: Hoffmann, Friedrich M.. City University Of New York; Estados UnidosFil: Furlong, Octavio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Física Aplicada; ArgentinaFil: Hrbek, Jan. Brookhaven National Laboratory; Estados UnidosFil: White, Michael G.. Brookhaven National Laboratory; Estados UnidosFil: Liu, Ping. Brookhaven National Laboratory; Estados UnidosFil: Stacchiola, Dario Jose. Brookhaven National Laboratory; Estados Unido

Assessment of NER solutions against the first and second CALBC Silver Standard Corpus

Background Competitions in text mining have been used to measure the performance of automatic text processing solutions against a manually annotated gold standard corpus (GSC). The preparation of the GSC is time-consuming and costly and the final corpus consists at the most of a few thousand documents annotated with a limited set of semantic groups. To overcome these shortcomings, the CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions, the first version of the Silver Standard Corpus (SSC-I). The four semantic groups are chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). This corpus has been used for the First CALBC Challenge asking the participants to annotate the corpus with their text processing solutions. Results All four PPs from the CALBC project and in addition, 12 challenge participants (CPs) contributed annotated data sets for an evaluation against the SSC-I. CPs could ignore the training data and deliver the annotations from their genuine annotation system, or could train a machine-learning approach on the provided pre-annotated data. In general, the performances of the annotation solutions were lower for entities from the categories CHED and PRGE in comparison to the identification of entities categorized as DISO and SPE. The best performance over all semantic groups were achieved from two annotation solutions that have been trained on the SSC-I. The data sets from participants were used to generate the harmonised Silver Standard Corpus II (SSC-II), if the participant did not make use of the annotated data set from the SSC-I for training purposes. The performances of the participants’ solutions were again measured against the SSC-II. The performances of the annotation solutions showed again better results for DISO and SPE in comparison to CHED and PRGE. Conclusions The SSC-I delivers a large set of annotations (1,121,705) for a large number of documents (100,000 Medline abstracts). The annotations cover four different semantic groups and are sufficiently homogeneous to be reproduced with a trained classifier leading to an average F-measure of 85%. Benchmarking the annotation solutions against the SSC-II leads to better performance for the CPs’ annotation solutions in comparison to the SSC-I

Appraisal of health care: from patient value to societal benefit

Aim: This paper summarizes the deficiencies and weaknesses of the most frequently used methods for the allocation of health-care resources. New, more transparent and practical methods for optimizing the allocation of these resources are proposed. Method: The examples of quality-adjusted life years (QALYs) and efficiency frontier (EF) are analyzed to describe weaknesses and problems in decisions regulating health-care provision. After conducting a literature search and discussions with an international group of professionals, three groups of professionals were formed to discuss the assessment and appraisal of health-care services and allocation of available resources. Results: At least seven essential variables were identified that should be heeded when applying the concept of QALYs for decisions concerning health-care provision. The efficiency frontier (EF) concept can be used to set a ceiling price and perform a cost-benefit analysis of provision, but different stakeholders—a biostatistician (efficacy), an economist (costs), a clinician (effectiveness), and the patient (value)—could provide a fairer appraisal of health-care services. Efficacy and costs are often based on falsifiable data. Effectiveness and value depend on the success with which a particular clinical problem has been solved. These data cannot be falsified. The societal perspective is generated by an informal cost-benefit analysis including appraisals by the above-mentioned stakeholders and carried out by an authorized institution. Conclusion: Our analysis suggests that study results expressed in QALYs or as EF cannot be compared unless the variables included in the calculation are specified. It would be far more objective and comprehensive if an authorized institution made an informal decision based on formal assessments of the effectiveness of health-care services evaluated by health-care providers, of the value assessed by consumers, of efficacy described by biostatisticians, and of costs calculated by economists

Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway

<p>Abstract</p> <p>Background</p> <p>To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).</p> <p>Methods</p> <p>Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.</p> <p>Results</p> <p>Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.</p> <p>Conclusions</p> <p>After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.</p

The ELIXIR Human Copy Number Variations Community:building bioinformatics infrastructure for research

Copy number variations (CNVs) are major causative contributors both in the genesis of genetic diseases and human neoplasias. While 'High-Throughput' sequencing technologies are increasingly becoming the primary choice for genomic screening analysis, their ability to efficiently detect CNVs is still heterogeneous and remains to be developed. The aim of this white paper is to provide a guiding framework for the future contributions of ELIXIR's recently established h uman CNV Community, with implications beyond human disease diagnostics and population genomics. This white paper is the direct result of a strategy meeting that took place in September 2018 in Hinxton (UK) and involved representatives of 11 ELIXIR Nodes. The meeting led to the definition of priority objectives and tasks, to address a wide range of CNV-related challenges ranging from detection and interpretation to sharing and training. Here, we provide suggestions on how to align these tasks within the ELIXIR Platforms strategy, and on how to frame the activities of this new ELIXIR Community in the international context

Automatic Filtering and Substantiation of Drug Safety Signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

Bid Regulates the Pathogenesis of Neurotropic Reovirus

Reovirus infection leads to apoptosis in both cultured cells and the murine central nervous system (CNS). NF-κB-driven transcription of proapoptotic cellular genes is required for the effector phase of the apoptotic response. Although both extrinsic death-receptor signaling pathways and intrinsic pathways involving mitochondrial injury are implicated in reovirus-induced apoptosis, mechanisms by which either of these pathways are activated and their relationship to NF-κB signaling following reovirus infection are unknown. The proapoptotic Bcl-2 family member, Bid, is activated by proteolytic cleavage following reovirus infection. To understand how reovirus integrates host signaling circuits to induce apoptosis, we examined proapoptotic signaling following infection of Bid-deficient cells. Although reovirus growth was not affected by the absence of Bid, cells lacking Bid failed to undergo apoptosis. Furthermore, we found that NF-κB activation is required for Bid cleavage and subsequent proapoptotic signaling. To examine the functional significance of Bid-dependent apoptosis in reovirus disease, we monitored fatal encephalitis caused by reovirus in the presence and absence of Bid. Survival of Bid-deficient mice was significantly enhanced in comparison to wild-type mice following either peroral or intracranial inoculation of reovirus. Decreased reovirus virulence in Bid-null mice was accompanied by a reduction in viral yield. These findings define a role for NF-κB-dependent cleavage of Bid in the cell death program initiated by viral infection and link Bid to viral virulence

Os registros conventuais como fonte para a história econômica: Aproximações metodológicas a partir do caso de Santa Fé (Argentina), 1700-1850

Objetivo/contexto: El artículo pone el foco en una problemática común a la historia económica de América Latina preestadística: la carestía de fuentes y las dificultades metodológicas para estudiar la evolución de los niveles de vida en el largo plazo. Metodología: Se parte para ello de un estudio de caso, la ciudad de Santa Fe, un enclave comercial del Río de la Plata tardocolonial, donde se asentaron cuatro órdenes religiosas desde el siglo XVII. Se exponen series seculares (1700-1850) de precios de dos alimentos básicos (yerba mate y azúcar), elaboradas a partir de libros contables de conventos, con la intención de demostrar las ventajas y las dificultades que presenta esta fuente para el estudio de los hábitos de consumo, la evolución de los precios de los alimentos y de las condiciones de vida en determinados ámbitos urbanos de la época colonial. La presentación incluye comparaciones de los precios en distintos conventos a lo largo del período, y se discuten específicamente las dificultades para la construcción de índices ponderados. Originalidad: Si bien se trata de una fuente ampliamente utilizada por la literatura académica que analizó el período, nunca se habían realizado comparaciones específicas entre las contabilidades de las distintas órdenes religiosas, en particular para una ciudad periférica del Virreinato del Río de la Plata. Conclusiones: Los resultados obtenidos no sólo muestran la utilidad de la fuente, sino también evidencian las dificultades que existen para la construcción de series que permitan analizar niveles de vida en el largo plazo. Alertan en este sentido sobre la necesidad de estudiar detalladamente las particularidades de cada caso antes de realizar grandes comparaciones internacionales.Objective/context: This article focuses on a problem common to the pre-statistical economic history of Latin America: the scarcity of sources and the methodological difficulties in studying the evolution of standards of living over time. Methodology: We begin with a case study done on the city of Santa Fe, a commercial enclave of the late-colonial Río de la Plata, where four religious orders had settled since the 17th century. Long-term records (1700-1850) from accounting books of convents, which included prices of two basic foodstuffs (yerba mate and sugar), are shown in order to demonstrate the advantages and difficulties of using this source in studying habits of consumption, the evolution of food prices and living conditions in certain urban areas of the colonial era. The exposition includes comparisons of the prices in different convents throughout the period, and specifically discusses the challenges in constructing the weighted indexes. Originality: Although these records are widely used by the academic literature analyzing this period, no specific comparisons had been made between the accounts of the different religious orders, particularly for a peripheral city of the Viceroyalty of the Río de la Plata. Conclusions: The final results show not only the usefulness of the source, but also the difficulties in constructing long run series to analyze living standards. Specific and detailed case studies are useful tools in order to improve broad international comparisons.Objetivo/contexto: O artigo coloca o foco numa problemática comum à história econômica da América Latina do período pré-estatístico: a falta de fontes e as dificuldades metodológicas para estudar a evolução dos níveis de vida a longo prazo. Metodologia: Para isso, parte-se de um estudo de caso: a cidade de Santa Fé, uma estratégica praça comercial do Rio da Prata no período colonial tardio, onde desde o século XVII se instalaram quatro ordens religiosas desde o século XVII. Apresentam-se séries seculares (1700-1850) de preços de dois alimentos básicos (erva-mate e açúcar), elaboradas a partir de livros contábeis de conventos, com a intenção de demonstrar as vantagens e as dificuldades que essa fonte apresenta para o estudo dos hábitos de consumo, da evolução dos preços dos alimentos e das condições de vida em determinados âmbitos urbanos da época colonial. O estudo inclui comparações dos preços em diferentes conventos ao longo do período e analisa vários quesitos que devem ser atendidos na construção de índices ponderados. Originalidade: Apesar de ser uma fonte amplamente utilizada pela literatura acadêmica que analisou o período, nunca foram realizadas comparações específicas entre as contabilidades das diferentes ordens religiosas, em particular para uma cidade periférica do Vice-reinado do Rio da Prata. Conclusões: Os resultados obtidos não somente mostram a utilidade da fonte, mas também evidenciam as dificuldades que existem para a construção de séries que permitam analisar níveis de vida a longo prazo. Alertam, nesse sentido, sobre a necessidade de estudar detalhadamente as peculiaridades de cada caso antes de realizar grandes comparações internacionais.Fil: Djenderedjian, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; ArgentinaFil: Frid, Carina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Martiren, Juan Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani". Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Historia Argentina y Americana "Dr. Emilio Ravignani"; Argentin

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology