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Orthorhombic crystals of paracetamol exhibit good technological properties during compression. The purpose of this study was to investigate the compression behavior of this substance and to compare it to that of monoclinic paracetamol. From the crystal structure, it could be hypothesized that sliding planes are present in the orthorhombic form, and could be responsible for an increase in crystal plasticity. Compression of pure orthorhombic or monoclinic paracetamol tablets was carried out on a fully instrumented single punch machine. Data was used to establish Heckel's profiles. Images of compressed crystals were obtained by scanning electron microscopy. Tabletability of the orthorhombic crystals was far better than that of the monoclinic ones, and capping was not observed even at high compression pressure. Compared to the monoclinic form, orthorhombic paracetamol exhibited greater fragmentation at low pressure, increased plastic deformation at higher pressure, and lower elastic recovery during decompression. Plastic behavior was confirmed by SEM - micrographs showing that crystals folded under pressure. A compactibility study showed that the nature of interparticle bonds was similar for both polymorphs, the number of bonds being greater for orthorhombic paracetamol. Unlike the monoclinic form, orthorhombic paracetamol is suitable for the direct compression process. The crystalline structure accounts for its better compression behavior, because of the presence of sliding planes.

The PICOSEC-Micromegas detector was developed for precise timing of the arrival of charged particles with a resolution bellow 30 ps. This contribution, after a brief introduction presents results concerning the PICOSEC-Micromegas response to single photoelectrons, estimation of the photoelectron yield of various photocathode types, as well as its performance to time the arrival of test beam muons. In addition, results based on detailed simulation studies and a stochastic model developed for the understanding of the detector are presented. Finally, results of studies related to the development of large scale PICOSEC-Micromegas detector for practical applications are also presented, in particular, the timing performance of a multi-channel PICOSEC prototype.

Detectors with a time resolution of 20-30 ps and a reliable performance in high particles flux environments are necessary for an accurate vertex separation in future HEP experiments. The PICOSEC-Micromegas detector concept is a Micro-Pattern Gaseous Detector (MPGD) based solution addressing this particular challenge. The PICOSEC-Micromegas concept is based on a Micromegas detector coupled to a Cherenkov radiator and a photocathode. In this detector concept, all primary electrons are initiated in the photocathode and the time jitter fluctuations are reduced. Different resistive anode layers have been tested with the goal of preserving a stable detector operation in a high intensity pion beam. One important characteristic of a gaseous detector in a high flux environment is the ion backflow (IBF). That can cause damage to more fragile photocathode materials like CsI. Various types of photocathode materials have been tested in order to find a robust solution against IBF bombardment.

During cholestasis, bile acids accumulate in the liver, and induce cellular alterations. Cholestasis is a major cause of liver fibrosis. We have used precision-cut liver slices (PCLS) in culture to investigate the effects of bile acids on hepatic cells. Rat PCLS were placed on an insert in a vial containing culture medium, and gently agitated on a roller platform. PCLS were treated with 100  μ M taurolithocholate (TLC), taurodeoxycholate (TDC) or taurocholate (TC) for 24 or 48 h. PCLS viability was measured, and immunohistochemistry was performed with antibodies against active caspase 3, platelet-derived growth factor (PDGF) receptor- β and ED-A fibronectin. TDC and TLC, two hydrophobic bile acids, induced hepatocyte necrosis and apoptosis, whereas TC, an hydrophilic bile acid, improved slice viability as compared with controls. Both TDC and TC induced biliary epithelial cell proliferation, together with portal fibroblast proliferation and activation, as shown by PDGF receptor- β and ED-A fibronectin expression. TLC induced biliary epithelial cell apoptosis. Our results indicate that individual bile acids induce cell type-specific effects in a complex liver microenvironment. The fact that PCLS support biliary epithelial cell and portal fibroblast proliferation will make this model very useful for the study of the mechanisms involved in portal fibrosis.

BackgroundEarly-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates.MethodsThis is a prospective observational study in neonates born at ≥34 weeks of gestation (WG). The primary endpoint was EOS, defined by isolation of pathogenic species from blood culture and/or cerebrospinal fluid culture within 72 hours after birth. Data on EOS were collected exhaustively from all maternity wards in Paris area (April 2019–March 2021).Results108 EOS were recorded (annual incidence, 0.32 per 1000 live births; 95% CI 0.26 to 0.38). In term infants, the most frequent pathogens were group B Streptococcus (GBS) (n=47) and Escherichia coli (n=20); in late preterm infants, the most frequent pathogens were E. coli (n=15) and GBS (n=7). Fifteen meningitis cases were diagnosed. Five E. coli strains (14%) were resistant to both amoxicillin and gentamicin, which is an empiric treatment for EOS. Of the 54 infants with GBS infections, 35 were born from mothers with negative GBS prepartum screening test and 8 from mothers with no screening. Two deaths were reported, both in term infants (Proteus mirabilis and E. coli).ConclusionIn neonates ≥34 WG born in the Paris area, GBS was twice as frequent as E. coli in term infants. EOS was six times more frequent in late preterm than in term infants and was due to E. coli in 60% of cases. Prevention of GBS EOS and empiric antibiotic treatment of EOS could be improved.

The ATLAS experiment at the Large Hadron Collider reads out 100 Million electronic channels at a rate of 200 Hz. Before the data are shipped to storage and analysis centres across the world, they have to be checked to be free from irregularities which render them scientifically useless. Data quality offline monitoring provides prompt feedback from full first-pass event reconstruction at the Tier-0 computing centre and can unveil problems in the detector hardware and in the data processing chain. Detector information and reconstructed proton-proton collision event characteristics are distilled into a few key histograms and numbers which are automatically compared with a reference. The results of the comparisons are saved as status flags in a database and are published together with the histograms on a web server. They are inspected by a 24/7 shift crew who can notify on-call experts in case of problems and in extreme cases signal data taking abort.

At the ATLAS experiment, the Detector Control System (DCS) is used to oversee detector conditions and supervise the running of equipment. It is essential that information from the DCS about the status of individual sub-detectors be extracted and taken into account when determining the quality of data taken and its suitability for different analyses. DCS information is written to the ATLAS conditions database and then summarised to provide a status flag for each sub-detector and displayed on the web. We discuss how this DCS information should be used, and the technicalities of making this summary.

Vitamin D, a molecule with antiproliferative, antiangiogenic, antioxidant and immunosuppressive effects, could play a role in the pathogenesis of severe diabetic retinopathy. We examined whether Taq I polymorphism of the vitamin D receptor is involved in the development of severe diabetic retinopathy. 200 unrelated C-peptide-negative French Type I diabetic patients were randomly selected (male:female, 103:97, age 44.4 +/- 12.4 years, diabetes duration: 27.7 +/- 10.0 years, BMI: 24.3 +/- 3.4 kg/m(2), HbA(1c): 8.6 +/- 1.3 %). The Taq I site was analysed by PCR followed by digestion with Taq I enzyme. Diabetic retinopathy was assessed by retinal angiography and classified as presence (n = 101) or absence (n = 99) of severe (preproliferative or proliferative) diabetic retinopathy. Frequency of wild-type genotype TT was lower in patients with severe diabetic retinopathy (n = 27) when compared with control subjects (n = 42, OR = 0.5, p = 0.028). Allele frequencies were not different between patients (T: n = 112 and t: n = 90) and control subjects (T: n = 128, and t: n = 70, p = 0.075). Global chi(2) (df = 2): p = 0.064. In subjects with diabetes duration of more than 25 years, TT was lower in severe diabetic retinopathy (n = 14) than control subjects (n = 18, OR = 0.3, p = 0.01). Allele frequencies were different between patients (T: n = 68 and t: n = 66) and control subjects (T: n = 52, OR = 0.5, and t: n = 26, OR = 1.9, p = 0.034). Global chi(2) (df = 2): p = 0.024. In subjects with HbA(1c) over 9 %, Tt was higher in patients (n = 28) than control subjects (n = 15, OR = 3.1, p = 0.019). Allele frequencies were not different between patients (T: n = 52 and t: n = 38) and control subjects (T: n = 57, and t: n = 29, p = 0.31). Global chi(2) (df = 2): p = 0.035. In French Type I (insulin-dependent) diabetic patients, we demonstrate an association between TT form (VDR) and low risk for severe diabetic retinopathy, especially in patients with long duration, and between Tt variant and high risk for severe diabetic retinopathy in subjects with poor glycaemic control.

Using the shell vial assay and sequence analysis of a variable region of the glycoprotein B (gB) gene, cytomegalovirus (CMV) excretion rates in urine and virus transmission were studied among 93 children from six day care centers (DCCs). During a 6-month period, excretion rates differed significantly between DCCs (P < .001). The 6 gB gene sequences, obtained from 24 CMV-infected children, were classified in four previously defined groups. In five DCCs, 2 or 3 strains cocirculated, and none was dominant. Infection could have been acquired outside the DCC for 2 children and inside it for 9. Two children from the same Dee had mixed infections. No differences in hygiene, child care practices, or experience and level of qualification of the staff could explain this wide variety of excretion rates between DCCs. The distribution of gB gene patterns observed does not suggest that 1 type was dominant or more efficiently transmitted.

We produced electrophoretic karyotypes of the reference strain E150 and of seven other isolates from different geographical origins to study the genomic organization of the dimorphic yeast Yarrowia lipolytica. These karyotypes differed in the number and size of the chromosomal bands. The karyotype of the reference stain E150 consisted of five bands of between 2.6 and 4.9Mb in size. This strain contained at least five rDNA clusters, from 190 to 620kb in size, which were scattered over most of the chromosomes. The assignment of 43 markers, including rRNA genes and three centromeres, to the E150 bands defined five linkage groups. Hybridization to the karyotypes of other isolates with pools of markers of each linkage group showed that linkage groups I, II, IV and V were conserved in the strains tested whereas group III was not and was split between at least two chromosomes in most strains. Use of a meganuclease I-SceI site targeted to one locus of E150 linkage group III showed that two chromosomes actually comigrated in band III of this strain. Our results are compatible with six chromosomes defining the haploid complement of strains of Y.lipolytica and that, despite an unprecedented chromosome length polymorphism, the overall structure of the genome is conserved in different isolates.[PUBLICATION ABSTRACT]