Miracle-dz/UniFAR-FTUs huggingface dataset:
PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish population.

OBJECTIVES The presence of anti-citrullinated peptide antibodies is the most specific serological marker known of rheumatoid arthritis (RA). The PADI4 gene, encoding a haematopoietic isoform of the peptidylarginine deiminase citrullinating enzyme, has recently been associated with susceptibility to RA in the Japanese population. A subsequent UK report could not confirm this association, and a later French study also yielded a negative result. Given this discrepancy and the importance of antibodies against citrullinated peptides in the early course of the disease, we performed a replication study. METHODS Three hundred and fifty-four Spanish RA patients and 498 Spanish controls were recruited from two Madrid hospitals. The padi4_104 and padi4_94 single-nucleotide polymorphisms (SNP) were analysed by TaqMan assays. RESULTS Similarly to what was described in the British and French population, the less frequent allele of this SNP was not associated with the disease (genotype TT, 16.1% in RA patients vs 14.3% in controls; P = 0.46, odds ratio 1.15, 95% confidence interval 0.78-1.71). A confirmatory negative result was obtained on analysing another SNP in the same gene, padi4_94, in 248 RA patients and 394 controls. CONCLUSIONS The results of our group and from the British and French studies strongly suggest that polymorphisms of the PADI4 gene do not play a role in susceptibility to RA in European populations.
Évaluation biopharmaceutique des antibiotiques pour le traitement des infections pulmonaires

Dans ce travail de these, l'efficacite de la voie intrapulmonaire et les parametres biopharmaceutiques influencant la diffusion pulmonaire apres nebulisation d'antibiotiques ont ete evalues. La presence et l'impact de certaines pompes d'efflux dans un modele in vitro de cellules primaires epitheliales pulmonaires de rat ont ete testes. Trois fluoroquinolones et la colistine ont ete utilisees comme molecules de reference. La combinaison des molecules testees a permis d'obtenir une vue d'ensemble des caracteristiques de diffusion intrapulmonaire des antibiotiques. L'etude in vivo avec les fluoroquinolones a demontre que les concentrations pulmonaires de ces molecules sont plus importantes que dans le plasma, probablement du a la presence des transporteurs comme la glycoproteine-P. La presence de ces transporteurs a ete confirmee dans le modele de cellules pulmonaires de rats. L'etude in vivo avec la colistine a montre qu'une lente diffusion pourrait conferer un avantage a la nebulisation par rapport a l'administration intraveineuse. En conclusion, l'administration par nebulisation des molecules, qui traversent les tissus lentement (colistine), pourrait etre avantageuse, alors que pour d'autres, qui traversent vite la barriere (fluoroquinolones), la voie nebulisee pourrait ne pas presenter des avantages par rapport a la voie intraveineuse. De plus, les resultats ont demontre qu'une faible permeabilite a travers le poumon (colistine) pourrait donner un avantage a la nebulisation des antibiotiques, tandis qu'une affinite pour des transporteurs (fluoroquinolones) semble presenter un interet aussi bien dans le cadre d'une nebulisation que d'une administration intraveineuse.
Serial population extinctions in a small mammal indicate Late Pleistocene ecosystem instability

The Late Pleistocene global extinction of many terrestrial mammal species has been a subject of intensive scientific study for over a century, yet the relative contributions of environmental changes and the global expansion of humans remain unresolved. A defining component of these extinctions is a bias toward large species, with the majority of small-mammal taxa apparently surviving into the present. Here, we investigate the population-level history of a key tundra-specialist small mammal, the collared lemming (Dicrostonyx torquatus), to explore whether events during the Late Pleistocene had a discernible effect beyond the large mammal fauna. Using ancient DNA techniques to sample across three sites in North-West Europe, we observe a dramatic reduction in genetic diversity in this species over the last 50,000 y. We further identify a series of extinction-recolonization events, indicating a previously unrecognized instability in Late Pleistocene small-mammal populations, which we link with climatic fluctuations. Our results reveal climate-associated, repeated regional extinctions in a keystone prey species across the Late Pleistocene, a pattern likely to have had an impact on the wider steppe-tundra community, and one that is concordant with environmental change as a major force in structuring Late Pleistocene biodiversity.
Research topics in software composition

Traditional software development approaches do not cope well with the evolving requirements of open systems. We argue that such systems are best viewed as flexible compositions of "software components" designed to work together as part of a component framework that formalizes a class of applications with a common software architecture. To enable such a view of software systems, we need appropriate support from programming language technology, software tools, and methods. We will briefly review the current state of object-oriented technology, insofar as it supports componentoriented development, and propose a research agenda of topics for further investigation.
Phase II study of low‐dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia

Resistance to imatinib is a frequent clinical problem in advanced phase chronic myelogenous leukemia (CML). A Phase II study was performed on low‐dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP).
Clinical work with suicide loss survivors: Implications of the U.S. postvention guidelines

ABSTRACT The loss of a loved one to suicide can present difficult challenges for suicide loss survivors (people bereaved by suicide) as well as for clinicians who would seek to help them. Building on the recommendations in the new document Responding to Grief, Trauma, and Distress after a Suicide: U.S. National Guidelines, this article provides an overview of clinical work with suicide loss survivors. It includes discussions of the common themes of suicide bereavement, the psychological tasks for integration of a suicide loss, and the options for providing grief therapy after a suicide. The article will be of value to caregivers who work with suicide loss survivors in counseling or therapeutic context.
Directions in brain injury research: From concept to clinical implementation

Development of rehabilitation treatments and services that are effective and supported by rigorous evidence is a long and multi-step process. Although there are similarities between this process and that used in pharmaceutical development, the sequence involved in developing this evidence in rehabilitation is more complex and less linear. The specific steps involved depend on a variety of factors including the location of the target of treatment within the International Classification of Functioning, Disability, and Health (ICF; World Health Organisation, 2006), the degree to which the treatment is guided by an underlying theory, the availability of animal models, and the plausibility of safety concerns. Similarly, the research designs chosen and the setting of the research vary both by treatment target and by maturity of the programme of evidence development. A full picture of the appropriate role and anticipated impact of specific rehabilitation treatments can benefit from a marriage between rehabilitation research (which seeks to understand how to change specific aspects of function), and enablement/disablement research (which seeks to understand how changes in one part of the ICF framework affect functioning elsewhere). Although the specific steps involved in a programmatic approach to rehabilitation treatment research vary, development of evidence about all treatments can benefit from a systematic programmatic approach in which each step seeks to answer specific questions and set the stage for subsequent investigation.
Implicaturas e a violação das máximas conversacionais: uma análise do humor em tirinhas

O presente trabalho tem por objetivo apresentar como o humor pode ser construido a partir de uma perspectiva pragmatica. Mais particularmente, buscaremos analisar como essa construcao se da atraves de implicaturas e violacoes das maximas conversacionais, elementos esses da Pragmatica Conversacional de Grice (1957; 1975). Para tal, utilizaremos como corpus de analise quatro tirinhas de humor de diferentes autorias. Sao elas duas tirinhas do Garfield – personagem criada pelo americano Jon Davies, no final da decada de 70 e publicada ate os dias atuais –, uma de humor meme – de autoria desconhecida por ser um estilo de tirinha que tem como caracteristica o fato de que pode ser produzida por qualquer internauta e divulgada na rede – e uma da Mafalda – personagem criada pelo argentino Quino e publicada originalmente entre os anos de 1964 e 1973.
Role of iron in regulation of virulence genes

The abilities of bacterial pathogens to adapt to the environment within the host are essential to their virulence. Microorganisms have adapted to the iron limitation present in mammalian hosts by evolving diverse mechanisms for the assimilation of iron sufficient for growth. In addition, many bacterial pathogens have used the low concentration of iron present in the host as an important signal to enhance the expression of a wide variety of bacterial toxins and other virulence determinants. The molecular basis of coordinate regulation by iron has been most thoroughly studied in Escherichia coli. In this organism, coordinate regulation of gene expression by iron depends on the regulatory gene, fur. Regulation of gene expression by iron in a number of pathogenic organisms is coordinated by proteins homologous to the Fur protein of E. coli. Additional regulatory proteins may be superimposed on the Fur repressor to provide the fine-tuning necessary for the precise regulation of individual virulence genes in response to iron and other environmental signals. Studies of the mechanisms of regulation of iron acquisition systems and virulence determinants by iron should lead to a better understanding of the adaptive response of bacteria to the low-iron environment of the host and its importance in virulence.
A Glial Fibrillary Acidic Protein‐Expressing and Tumorigenic Cell Line Derived from an Avian Sarcoma Virus‐Induced Rat Astrocytoma

A permanent cell line, S635c15, was derived from an anaplastic astrocytoma induced by the Schmidt-Ruppin strain of avian sarcoma virus (ASV) in a female F-344 rat. Persistent expression of the astrocytic differentiation protein, glial fibrillary acidic protein (GFAP), was detected both in cultured cells after 100 passages in vitro and in transplanted tumors. Subcutaneous and intracerebral transplantation of S635c15 cells in syngeneic rats resulted in a 100% tumor incidence and a reproducible mortality distribution. S635c15 cells formed discrete masses after subcutaneous injection but grew intracranially as infiltrative lesions. Tumor blood flow and blood-to-tissue transport studies yield comparable values to other rat glioma models; S635c15 intracranial tumors proved to be a homogeneous model with little variation within and between tumors with respect to morphology, GFAP expression, blood flow, and permeability. This cell line provides a GFAP-expressing brain tumor model that extends the use of autochthonous ASV-induced astrocytomas by allowing in vitro and in vivo studies. It may be useful for further studies in neurobiology and brain tumor biology, diagnosis, and therapy.
erioperative Management of Hepatic Resection oward Zero Mortality and Morbidity : Analysis of 93 Consecutive Cases in a Single Institution

BACKGROUND: The mortality rates associated with hepatectomy are still not zero. Our aim was to define the risk factors for complications and to evaluate our perioperative management. STUDY DESIGN: Between 2001 and 2008, 793 consecutive patients (547 men and 246 women; mean age SD, 56.1 14.9 years) underwent hepatectomy without gastrointestinal resection and choledocojejunostomy at our center. Of these patients, 354 (44.6%) were positive for the hepatitis B virus surface antigen and/or the hepatitis C virus antibody. We categorized 783 (98.7%) patients as Child-Pugh class A. Major resection (sectionectomy, hemihepatectomy, and extended hemihepatectomy), was performed in 535 patients (67.5%) and re-resection in 81 patients (10.2%). RESULTS: The median operative time was 345.5 minutes and median blood loss was 360 mL. The rate of red blood cell transfusion was 6.8%. The morbidity rate was 15.6%. Reoperations were performed in 19 patients (2.4%). The mean postoperative hospital stay was 18.4 10.4 days. The in-hospital mortality rate was 0.1% (1 of 793 patients; caused by hepatic failure). The independent relative risk for morbidity was influenced by an operative time of more than 360 minutes, blood loss of more than 400 mL, and serum albumin levels of less than 3.5 g/dL, as determined using multivariate logistic regression analysis. CONCLUSIONS: Shorter operative times and reduced blood loss were obtained by improving the surgical technique and using new surgical devices and intraoperative management, including anesthesia. Additionally, decision making using our algorithm and perioperative management according to CDC guidelines reduced the morbidity and mortality associated with hepatectomy. (J Am Coll Surg 2010;211:443–449. © 2010 by the American College of Surgeons)
Uplink performance of cellular massive MIMO with fractional power control: Asymptotic analysis

This paper addresses the spatial-average analysis of uplink signal to interference ratio (SIR) and throughput in massive MIMO networks with maximum ratio combining (MRC). The analysis incorporates the effects of fractional power control (FPC) and other cells interference (ICI) due to estimation error in channel state information (CSI). Based on an asymptotic approach, tractable expressions are presented for SIR-distributions and specific performance metrics (coverage probability and average rate) in poisson topology model. Moreover, the considered approach is applicable both to random and deterministic network topologies. The impacts of key network-features such as FPC, path-loss exponent and base station (BS) density are characterized. Numerical results validate the model and show that the coverage probability in lower 50th percentile can be maximized by adjusting FPC compensation-fraction between 0.2 and 0.5 depending on the system parameters. Also, for SIR threshold of 0 dB, allocating FPC of 0.25 for uplink transmit power can achieve approximately 6% improvement in coverage probability in cell edge area compared to constant-power policy and about 14% improvement compared to full channel-inversion policy. The provided approximation results can replace the need for lengthy-Monte-Carlo simulations in designing of large scale MIMO systems and quantify the trade-off between improved cell-edge SIR for low and moderate values of FPC.
Mass spectrometry for malaria diagnosis

A physical method currently being developed for malaria parasite detection and diagnosis in blood is reviewed in this article. The method – direct laser desorption mass spectrometry – is based on the detection of heme (iron protoporphyrin) as a unique qualitative and quantitative molecular biomarker for malaria. In infected erythrocytes, the parasite sequesters heme in a molecular crystal (hemozoin) – a volume of highly concentrated and purified biomarker molecules. Laser desorption mass spectrometry detects only heme from hemozoin in parasite-infected blood, and not heme that is bound to hemoglobin or other proteins in uninfected blood samples. The method requires only a drop of blood with minimal sample preparation. Laser desorption mass spectrometry may become a rapid and high-throughput tool for specific and sensitive pan-malaria detection at levels below 10 parasites/μl of blood.
datumPIPE: Data Generator and Corrupter for Multiple Data Quality Aspects

Organizations use data to support different business processes. Data may become unclean because of corruptions in the central quality aspects due to factors such as duplicate records, outdated data, inconsistent values, incomplete information, or inaccurate values. Real datasets are usually not available for reasons such as privacy constraints. In the existing systems that generate or corrupt synthetic data, the intrinsic characteristics of data may not satisfy the quality aspects, and the injected types of errors do not corrupt multiple data quality aspects. Also, a lack of common datasets is a primary reason that representative comparisons between algorithms of different data quality management approaches are not possible. To address these issues, we present datumPIPE, a system that allows for the generation of data that satisfies a set of integrity constraints, including functional dependencies (FDs), conditional functional dependencies (CFDs), and inclusion dependencies (INDs). Also, datumPIPE provides the functionality to generate other types of attribute values such as sensors and personal data. It also allows for the corruption of the generated data through the introduction of quality issues in the central data quality aspects.
Alveolar and serum oxidative stress in ventilator-associated pneumonia.

BACKGROUND In several lung diseases, oxidative stress can be demonstrated. This has not been shown in patients with ventilator-associated pneumonia (VAP). METHODS We studied plasma and bronchoalveolar lavage (BAL) samples for markers of oxidative stress, taken from patients with VAP. Seventy-eight patients likely to have VAP and 10 patients who were not suspected of having VAP were studied prospectively. A diagnosis of VAP was based on a positive quantitative mini-lavage culture of > or = 10(3) colony-forming units per ml. Blood and BAL samples were collected and analysed for thiobarbituric acid reactant substances (TBARS) and antioxidant activity. RESULTS Plasma and alveolar TBARS increased significantly in patients who developed VAP compared with those who did not, by 43% and 259% respectively. Red cells and alveolar glutathione peroxidase concentrations (antioxidant activity) were lower in those with VAP compared with the non-VAP group, by 43% and 68% respectively. No significant differences were found for serum superoxide dismutase activity. Significant differences were found for alveolar glutathione peroxidase concentrations over time in the VAP group. No significant differences between survivors and non-survivors were found in the blood or BAL assays, in patients with VAP. CONCLUSIONS VAP is associated with evidence of early oxidative stress in the alveolar fluid and blood.
Electrical activity and postsynapse formation in adult muscle: gamma-AChRs are not required.

Skeletal muscle fibers will not accept hyperinnervation by foreign motor axons unless they are paralyzed, suggesting that paralysis makes them receptive to innervation, e.g., by upregulating extrasynaptic expression of gamma-AChRs and/or of the agrin receptor MuSK. To examine the involvement of these parameters in paralysis-mediated synapse induction, ectopic expression of agrin, a factor from motor neurons controlling neuromuscular synapse formation, was made dependent on the administration of doxycycline in innervated adult muscle fibers. In response to doxycycline-induced agrin secretion, adult fibers did form ectopic postsynaptic specializations, even when they were electrically active, lacked fetal AChRs, and expressed normal low levels of MuSK. These data demonstrate that paralysis and changes associated with it are not required for agrin-induced postsynapse formation. They suggest that paralyzed muscle induces synapse formation via the release of factors that make motor neurites contact muscle fibers and secrete agrin.
The LuxS‐dependent autoinducer AI‐2 controls the expression of an ABC transporter that functions in AI‐2 uptake in Salmonella typhimurium

In a process called quorum sensing, bacteria communicate with one another using secreted chemical signalling molecules termed autoinducers. A novel autoinducer called AI‐2, originally discovered in the quorum‐sensing bacterium Vibrio harveyi, is made by many species of Gram‐negative and Gram‐positive bacteria. In every case, production of AI‐2 is dependent on the LuxS autoinducer synthase. The genes regulated by AI‐2 in most of these luxS‐containing species of bacteria are not known. Here, we describe the identification and characterization of AI‐2‐regulated genes in Salmonella typhimurium. We find that LuxS and AI‐2 regulate the expression of a previously unidentified operon encoding an ATP binding cassette (ABC)‐type transporter. We have named this operon the lsr (luxS regulated) operon. The Lsr transporter has homology to the ribose transporter of Escherichia coli and S. typhimurium. A gene encoding a DNA‐binding protein that is located adjacent to the Lsr transporter structural operon is required to link AI‐2 detection to operon expression. This gene, which we have named lsrR, encodes a protein that represses lsr operon expression in the absence of AI‐2. Mutations in the lsr operon render S. typhimurium unable to eliminate AI‐2 from the extracellular environment, suggesting that the role of the Lsr apparatus is to transport AI‐2 into the cells. It is intriguing that an operon regulated by AI‐2 encodes functions resembling the ribose transporter, given recent findings that AI‐2 is derived from the ribosyl moiety of S‐ribosylhomocysteine.
Synthèse de réseaux de neurones par codage cellulaire et algorithmes génétiques

Autrefois consideres comme une machine vouee a un apprentissage realise a l'aide de petites modifications successives de parametres, les reseaux de neurones artificiels sont en train de changer de statut. De telles methodes d'apprentissage ne permettent pas en effet de generer de gros reseaux necessaire a la resolution de problemes consequents. Cette these soutient les trois points de vue suivant: 1) le mot cle pour sortir de l'impasse est modularite. 2) l'outil cle pour generer des reseaux de neurones modulaires est le codage cellulaire. 3) la methode d'optimisation cle pour explorer l'espace de recherche des codes cellulaires est l'algorithme genetique. Le premier point est une idee a present repandue. Par reseaux de neurones modulaires, on entend un reseau de neurones se decomposant en sous-reseaux, d'une facon hierarchique, avec des sous-reseaux qui peuvent se repeter. Cette these se decompose en deux parties. La premiere partie demontre le deuxieme point. Le codage cellulaire est presente comme un veritable langage machine de reseaux de neurones, avec des fondements theoriques (c'est en fait une grammaire de graphe, verifiant un certain nombre de proprietes) et un compilateur de langage evolue. La deuxieme partie demontre le troisieme point. L'application des algorithmes genetiques a la synthese de reseaux de neurones en utilisant le codage cellulaire est une nouvelle technologie. Cette technologie permet de resoudre des problemes encore jamais resolus. Elle peut automatiquement et dynamiquement decomposer un probleme en une hierarchie de sous-problemes, et generer un reseau de neurones dont la structure hierarchique de sous-reseaux reflete celle du probleme. Elle permet d'experimenter des domaines de recherche encore vierges comme par exemple, l'interaction entre apprentissage genetique et apprentissage de poids ou la mise au point d'apprentissages connectionnistes adaptes a l'algorithme genetique