Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential factors associated with challenge‐proven food allergy phenotypes in a population cohort of infants: a latent class analysis

Food allergy, eczema and wheeze are early manifestations of allergic disease and commonly co‐occur in infancy although their interrelationship is not well understood. Data from population studies are essential to determine whether there are differential drivers of multi‐allergy phenotypes. We aimed to define phenotypes and risk factors of allergic disease using latent class analysis (LCA).
Horizontal gene transfer in the innovation and adaptation of land plants

Horizontal gene transfer (HGT) has been well documented in prokaryotes and unicellular eukaryotes, but its role in plants and animals remains elusive. In a recent study, we showed that at least 57 families of nuclear genes in the moss Physcomitrella patens were acquired from prokaryotes, fungi or viruses and that HGT played a critical role in plant colonization of land. In this paper, we categorize all acquired genes based on their putative functions and biological processes, and further address the importance of HGT in plant innovation and evolution.
Inférence sur réseaux géniques par Analyse en Facteurs

La technologie des puces a ADN permet l'analyse simultanee du niveau d'expression de plusieurs milliers de genes. Un des enjeux de l'analyse de ce type de donnees est de comprendre la structure de dependance, qui rend compte des relations biologiques entre les genes. En particulier, on s'interesse ici a la modelisation du reseau de regulation des genes impliques dans le controle d'un caractere phenotypique. Dans un premier temps, on definit un cadre general pour la prise en compte de la dependance par l'identification de facteurs latents, modelisant la variation commune a l'ensemble des genes. On montre que l'introduction de ces facteurs dans les procedures d'analyse differentielle en ameliore la puissance ainsi que la stabilite des taux d'erreurs. De plus, dans le contexte des modeles graphiques gaussiens pour la modelisation des reseaux d'interactions entre genes, on presente une methode d'estimation des correlations partielles s'appuyant sur la reduction de la dimension des donnees par les variables latentes. La methode est illustree par son application a une etude visant a identifier les genes impliques dans le metabolisme des lipides chez le poulet (UMR INRA Genetique Animale de Rennes).
Multifocal osteomyelitis and erythematous plaque associated with Yersinia pseudotuberculosis infection

and domestic animals. In humans it causes varying degrees of illness including diarrhea and also systemic manifestations, such as Kawasaki disease, erythema nodosum, arthritis, coronary aneurysms and acute renal failure.1–4 However, no study has suggested the involvement of Y. pseudotuberculosis in the pathogenesis of chronic recurrent multifocal osteomyelitis (CRMO). This disease was first described by Giedion et al. and recurrently develops an inflammatory bone disease resembling infectious osteomyelitis, but without an identifiable infectious agent.5 Cultures of the involved sites are sterile and the patients do not respond to antibiotics.6 The clinical course was characterized by intermittent periods of exacerbation and improvement over several years. The disease is frequently accompanied by neutrophilic skin lesions such as palmoplantar pustulosis and Sweet syndrome. Although several mechanisms, such as Mycoplasma, Chlamydia, virus infection and autoimmunity, have been suggested to be involved, the precise mechanism remains to be elucidated.5–7 We describe a 15-year-old girl who developed fever, aseptic inflammation at multiple sites of the bone and erythematous plaques, and was diagnosed with Y. pseudotuberculosis infection based on her clinical course and serum antibody titers. These manifestations were consistent with the first episode of CRMO. The relationship between CRMO and Y. pseudotuberculosis is discussed. Case report
Capecitabine as adjuvant treatment for stage III colon cancer.

BACKGROUND Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. METHODS We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P<0.001). CONCLUSIONS Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.
Glycosylation pattern and cell attachment-inhibiting property of human salivary mucins.

BACKGROUND Whole human saliva (WHS) and its high molecular weight mucin constituent (Muc) inhibit fibroblast attachment and might influence periodontal and peri-implant wound healing. The aim of this work was to study the potential role of glycosylation of Muc in fibroblast attachment-inhibiting property and to examine in vitro the effect of WHS and Muc on epithelial cell attachment. METHODS Muc was isolated from WHS by CsCl density gradient ultracentrifugation; covalently immobilized on polystyrene; and subjected to enzymic digestion by N-glycanase, O-glycanase, and sialidase, or chemical desulfation and periodate treatment. Wells of tissue culture microtiter plates were incubated with WHS, Muc, or buffer as control; suspensions of normal human oral keratinocytes, spontaneously immortalized human keratinocytes, or human gingival fibroblasts were applied; and cell attachment determined using methylene blue assay. RESULTS While enzymic cleavage of N-linked carbohydrates showed no effect, selective removal of O-linked residues and sialic acid as well as desulfation and periodate oxidation resulted in statistically significant reduction of cell attachment-inhibiting property of immobilized Muc. Significantly lower numbers of attached cells of each cell type were found in wells pretreated with WHS or Muc. CONCLUSIONS Inhibition of cell attachment may be mediated by the carbohydrate residues suggesting specific interactions between the salivary constituent and the cell surface. Exposure of root and implant surfaces to saliva during early wound healing events might influence healing by inhibiting surface colonization by oral keratinocytes and fibroblasts, and enhancing wound repair in the form of long junctional epithelium rather than regeneration.
MalT, the regulatory protein of the Escherichia coli maltose system, is an ATP‐dependent transcriptional activator.

We show that MalT, the transcriptional activator of the Escherichia coli maltose regulon, specifically binds ATP and dATP with a high affinity (Kd = 0.4 microM) and exhibits a weak ATPase activity. Using an abortive initiation assay, we further show that activation of open complex formation by MalT depends on the presence of ATP in addition to that of maltotriose, the inducer of the maltose system. Similar experiments in which ATP was replaced by ADP or AMP‐PNP, a non‐hydrolysable analogue of ATP, demonstrate that this reaction does not require ATP hydrolysis. As revealed by DNase I footprinting, both ATP and maltotriose are required for the binding of the MalT protein to the mal promoter DNA.
Trans‐4‐hydroxy‐2‐hexenal is a neurotoxic product of docosahexaenoic (22:6; n‐3) acid oxidation

Lipid peroxidation of docosahexaenoic (22:6; n‐3) acid (DHA) is elevated in the CNS in patients with Alzheimer’s disease and in animal models of seizure and ethanol withdrawal. One product of DHA oxidation is trans‐4‐hydroxy‐2‐hexenal (HHE), a six carbon analog of the n‐6 fatty acid derived trans‐4‐hydroxy‐2‐nonenal (HNE). In this work, we studied the neurotoxic potential of HHE. HHE and HNE were toxic to primary cultures of cerebral cortical neurons with LD50’s of 23 and 18 μmol/L, respectively. Toxicity was prevented by the addition of thiol scavengers. HHE and HNE depleted neuronal GSH content identically with depletion observed with 10 μmol/L of either compound. Using an antibody raised against HHE–protein adducts, we show that HHE modified specific proteins of 75, 50, and 45 kDa in concentration‐ and time‐dependent manners. The time‐dependent formation of HHE differed from that of F4‐neuroprostanes following in vitro DHA oxidation likely as a result of the different oxidation pathways involved. Using purified mitochondrial aldehyde dehydrogenase ALDH5A, we found that HHE was oxidized 6.5‐fold less efficiently than HNE. Our data demonstrate that HHE and HNE have similarities but also differences in their neurotoxic mechanisms and metabolism.
Endothelial Dysfunction in Diabetes and Hypertension: Cross Talk in RAS, BMP4, and ROS-dependent COX-2–derived Prostanoids

Abstract: Vascular endothelium regulates cardiovascular function, and endothelial dysfunction is the key initiator for arteriosclerosis and thrombosis and their complications. The endothelium is a dynamic interface that responds to various stimuli and synthesizes and liberates vasoactive molecules such as nitric oxide, prostaglandins, hyperpolarizing factor, and endothelin. Risk factors such as hypertension, hypercholesterolemia, smoking, and hyperglycemia impair the ability of the endothelium to respond to physical or chemical stimulation appropriately, and increased oxidative stress is believed to be a major culprit. This brief article reviews the interplay among several oxidative stress regulators in the vascular wall and highlights therapeutic relevance through deeper understanding of the interplay between the renin–angiotensin system, nicotinamide adenine dinucleotide phosphate, reduced oxidase, bone morphogenic protein 4, and cyclooxygenase 2–derived prostaglandins as a concerted pathogenic cascade in inducing and maintaining endothelial dysfunction in hypertension and diabetes.
Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Reduces Microglial and Astroglial Inflammatory Responses1

Upon activation, microglia and astrocytes produce a number of proinflammatory molecules that participate in the pathophysiology of several neurodegenerative disorders. This study explores the anti-inflammatory property of cinnamon metabolite sodium benzoate (NaB) in microglia and astrocytes. NaB, but not sodium formate, was found to inhibit LPS-induced expression of inducible NO synthase (iNOS), proinflammatory cytokines (TNF-α and IL-1β) and surface markers (CD11b, CD11c, and CD68) in mouse microglia. Similarly, NaB also inhibited fibrillar amyloid β (Aβ)-, prion peptide-, double-stranded RNA (polyinosinic-polycytidylic acid)-, HIV-1 Tat-, 1-methyl-4-phenylpyridinium+-, IL-1β-, and IL-12 p402-induced microglial expression of iNOS. In addition to microglia, NaB also suppressed the expression of iNOS in mouse peritoneal macrophages and primary human astrocytes. Inhibition of NF-κB activation by NaB suggests that NaB exerts its anti-inflammatory effect through the inhibition of NF-κB. Although NaB reduced the level of cholesterol in vivo in mice, reversal of the inhibitory effect of NaB on iNOS expression, and NF-κB activation by hydroxymethylglutaryl-CoA, mevalonate, and farnesyl pyrophosphate, but not cholesterol and ubiquinone, suggests that depletion of intermediates, but not end products, of the mevalonate pathway is involved in the anti-inflammatory effect of NaB. Furthermore, we demonstrate that an inhibitor of p21ras farnesyl protein transferase suppressed the expression of iNOS, that activation of p21ras alone was sufficient to induce the expression of iNOS, and that NaB suppressed the activation of p21ras in microglia. These results highlight a novel anti-inflammatory role of NaB via modulation of the mevalonate pathway and p21ras.
Stereochemical pharmacokinetics of the 2-arylpropionic acid non-steroidal antiinflammatory drug flunoxaprofen in rats and in man.

Stereospecific serum assays of the non-steroidal antiinflammatory drug flunoxaprofen (S(+)-2-(4-fluorophenyl)-a-methyl-5-benzoxazoleacetic acid, Priaxim) were performed in rats after the oral administration of 10 mg/kg b.w. of the different enantiomeric forms of the drug or of the racemate in order to establish the occurrence and the rate of biotransformation of R(-)-flunoxaprofen to the S(+)-enantiomer, which is the pharmacologically active form. Preliminary observations of the enantiomeric blood levels were also made in man after a single oral dose (100 mg) of R(-)-flunoxaprofen or of the racemate. Blood was withdrawn at different time intervals up to 120 h in rats and up to 48 h in man and serum levels of flunoxaprofen enantiomers were determined by a HPLC method. The results obtained in the rat show that S(+)-flunoxaprofen serum levels following the administration of a single oral dose of flunoxaprofen reach about the same values (between 24 and 30 micrograms/ml at 18 h) whichever form was dosed (i.e. 10 mg/kg b.w. of S(+)- or R(+)-, or 5 mg/kg b.w. of S(+)- as the racemate). On the contrary, R(-)-flunoxaprofen serum concentrations fall to values lower than 5 micrograms/ml either after the administration of 10 mg/kg R(-)- or of 5 mg/kg R(-)- as the racemate; these serum R(-)-flunoxaprofen values are close to those observed after the administration of S(+)-flunoxaprofen which contains 5% R(-)- as an impurity (i.e. 0.5 mg/kg b.w.). (ABSTRACT TRUNCATED AT 250 WORDS)
Optimizing Geometric Multigrid Method Computation using a DSL Approach

The Geometric Multigrid (GMG) method is widely used in numerical analysis to accelerate the convergence of partial differential equations solvers using a hierarchy of grid discretizations. Multiple grid sizes and recursive expression of multigrid cycles make the task of program optimization tedious. A high-level language that aids domain experts for GMG with effective optimization and parallelization support is thus valuable. We demonstrate how high performance can be achieved along with enhanced programmability for GMG, with new language/optimization support in the PolyMage DSL framework. We compare our approach with (a) hand-optimized code, (b) hand-optimized code in conjunction with polyhedral optimization techniques, and (c) the existing PolyMage optimizer adapted to multigrid. We use benchmarks varying in multigrid cycle structure and smoothing steps for evaluation. On a 24-core Intel Xeon Haswell multicore system, our automatically optimized codes achieve a mean improvement of 3. 2x over straightforward parallelization, and 1. 31x over the PolyMage optimizer.CCS CONCEPTS• Software and its engineering →Compilers;
Clinical implications of SOCS1 methylation in myelodysplastic syndrome

The suppressor of cytokine signalling‐1 (SOCS1) protein is a tumour suppressor. Hypermethylation of SOCS1 gene, resulting in transcriptional silencing, is suggested to play an important role in cancer development. We sought to characterise SOCS1 methylation in primary myelodysplastic syndrome (MDS) and clarify its clinical implications. The methylation status of SOCS1 was analysed by methylation‐specific polymerase chain reaction in 114 patients with primary MDS and serial studies were performed in 29 of them. SOCS1 methylation occurred in 54 patients (47·4%), and was more frequent in patients with high‐risk MDS than in those with low‐risk (52·6% vs. 25·8%, P = 0·011). SOCS1 methylation was closely associated with NRAS mutation (P = 0·010) and inversely associated with good‐risk karyotype (P = 0·021). With a median follow‐up of 17 months (range: 1–231 months), two patients acquired SOCS1 methylation during disease progression. In two patients, SOCS1 methylation present at diagnosis, disappeared after haematopoietic stem cell transplantation. Patients with SOCS1 methylation had a higher cumulative risk of leukaemic transformation than those without (55·8% vs. 27·7% at 3 years, P = 0·004). This difference remained significant within the subgroup of patients with high‐risk MDS (67·3% vs. 45·1% at 3 years, P = 0·045). This is the first report to demonstrate the clinical relevance of SOCS1 methylation in MDS. It may play an important role in the pathogenesis of MDS, especially among patients with high‐risk subtypes.
Evaluación de la evolución del diseño en F/OSS: un caso de estudio

En los ultimos anos El F/OSS se convirtio en una alternativa viable tanto para la provision de software como para la reutilizacion en la creacion de nuevos productos. Dada la enorme heterogeneidad de los productos F/OSS, se vuelve necesaria la busqueda de metodos para evaluar estos productos. Nos proponemos aqui explorar la informacion que puede obtenerse de un producto F/OSS utilizando una serie de metricas que permitan sacar conclusiones respecto de la evolucion del codigo fuente. Tomamos como caso de estudio la aplicacion Sweet Home 3D, una aplicacion para diseno de interiores escrita en Java y alojada en el repositorio SourceForge, Realizamos las mediciones y el procesamiento estadistico mediante herramientas de libre disponibilidad, a fin de facilitar la replicacion del estudio o comparar con estudios similars. Posteriormente efectuamos el analisis de los datos obtenidos, observando una correlacion lineal entre las variables consideradas para los valores registrados en este caso. Esto nos permitira a futuro poder cotejar los resultados con experiencias similares.
Contrôle latéral et longitudinal pour le suivi de véhicule

Cette these s’inscrit dans le contexte de l’Automatisation des vehicules a basses vitesses. L'objectif de la these est centre sur l'automatisation de la conduite, ce qui permettra une amelioration des conditions de circulation en gardant la securite des passagers. La consequence sera un allegement du trafic avec une reduction du stress affectant les conducteurs. Il s'avere alors necessaire de disposer de techniques fiables, robustes et performantes. Dans cette optique, ces travaux de these sont subdivises en trois volets. Un premier volet a ete consacre a la modelisation (couplage des dynamiques laterale et longitudinale) et au positionnement du vehicule sur la route. Le deuxieme volet traite le probleme de reconstruction de variables non mesurables dans le vehicule. En effet, la commande des systemes dynamiques requiert souvent la connaissance de variables qui ne sont pas accessibles directement pour des raisons diverses et variees (techniques et economiques). D'ou la necessite de disposer d'un algorithme pour reconstruire ces variables inconnues a partir de variables mesurables. La technique d'observateurs par modes glissants a ete choisie alors pour traiter ce probleme. Un tel choix est justifie par sa robustesse et par sa simplicite. Le troisieme volet est dedie a la conception et synthese de lois de commande. Deux approches de commandes non lineaires robustes ont ete proposees afin de traiter le probleme : les modes glissants d’ordre 1 et 2 et la technique du backstepping ont ete adaptes au controle combine lateral et longitudinal du vehicule. Des tests en simulation ont ete effectues sur plusieurs scenarios de suivi de vehicule (manœuvre de changement de voie, changement de direction, manœuvre combinee, etc. ) pour evaluer le comportement des lois de commande proposees en termes de performance et de robustesse
Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model.

BACKGROUND AIMS Tumor antigen-specific cytotoxic T lymphocytes (CTL) have been used in the treatment of human cancer, including leukemia. Several studies have established PR1 peptide, an HLA-A2.1-restricted peptide derived from proteinase 3 (P3), as a human leukemia-associated antigen. PR1-specific CTL elicited in vitro from healthy donors have been shown to lyse P3-expressing AML cells from patients. We investigated whether PR1-CTL can be adoptively transferred into NOD/SCID mice to eliminate human leukemia cells. METHODS PR1-CTL were generated in bulk culture from peripheral blood mononuclear cells (PBMC) stimulated with autologous dendritic cells. Human acute myeloid leukemia (AML) patient samples were injected and engrafted in murine bone marrow at 2 weeks post-transfer. RESULTS Following adoptive transfer, bone marrow aspirate from mice that received AML alone had 72-88% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 3-18% blasts in a hypocellular marrow. The PR1-CTL persisted in the bone marrow and liver and maintained a CD45RA⁻CD28+ effector phenotype. CONCLUSIONS We found that adoptive transfer of PR1-CTL generated in vitro is associated with reduced AML cells in NOD/SCID mice. PR1-CTL can migrate to the sites of disease and maintain their capacity to kill the AML cells. The surface phenotype of PR1-CTL was consistent with their trafficking pattern in both vascular and end-organ tissues.
Low Cost Memristor Associative Memory Design for Full and Partial Matching Applications

Novel memory circuits based on variable-resistance devices (such as memristors) have been recently proposed to overcome the limitations of CMOS based memories. These novel memories although based on different technologies, all share the principle of storing information as the resistance value imposed to a variable-resistance devices. Another promising application of memristors is in content-addressable memory (CAM). The study of memristor based CAM design has become increasingly important with the advent of new hybrid CMOS molecular technologies. To this end, we present a two-transistor-memristor (2T2M) bitcell for CAM design, suitable for low-power applications. The proposed circuit consists of memristors to store data and transistors as access devices, and utilizes complementary logic values at the input. We present detailed simulation based characterization (for both full match and partial match cases) and analysis, considering different word sizes of the proposed bitcells, including full parasitics, using BPTM 45-nm CMOS device models.