The Weierstrass subgroup of a curve has maximal rank

We show that the Weierstrass points of the generic curve of genus $g$ over an algebraically closed field of characteristic 0 generate a group of maximal rank in the Jacobian

Hand rub dose needed for a single disinfection varies according to product: A bias in benchmarking using indirect hand hygiene indicator

AbstractBackgroundThe 3ml volume currently used as the hand hygiene (HH) measure has been explored as the pertinent dose for an indirect indicator of HH compliance. A multicenter study was conducted in order to ascertain the required dose using different products.MethodThe average contact duration before drying was measured and compared with references. Effective hand coverage had to include the whole hand and the wrist. Two durations were chosen as points of reference: 30s, as given by guidelines, and the duration validated by the European standard EN 1500. Each product was to be tested, using standardized procedures, by three nosocomial infection prevention teams, for three different doses (3, 2 and 1.5ml).ResultsData from 27 products and 1706 tests were analyzed. Depending on the product, the dose needed to ensure a 30-s contact duration in 75% of tests ranging from 2ml to more than 3ml, and to ensure a contact duration exceeding the EN 1500 times in 75% of tests ranging from 1.5ml to more than 3ml. The aftermath interpretation is the following: if different products are used, the volume utilized does not give an unbiased estimation of the HH compliance. Other compliance evaluation methods remain necessary for efficient benchmarking

Transcriptional profiling of Actinobacillus pleuropneumoniae during the acute phase of a natural infection in pigs

<p>Abstract</p> <p>Background</p> <p><it>Actinobacillus pleuropneumoniae </it>is the etiological agent of porcine pleuropneumonia, a respiratory disease which causes great economic losses worldwide. Many virulence factors are involved in the pathogenesis, namely capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In order to identify genes that are expressed <it>in vivo </it>during a natural infection, we undertook transcript profiling experiments with an <it>A. pleuropneumoniae </it>DNA microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of <it>App </it>serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in length.</p> <p>Results</p> <p>Transcriptional profiling of <it>A. pleuropneumoniae </it>recovered from the lung of a pig suffering from a natural infection or following growth of the bacterial isolate in BHI medium was performed. An RNA extraction protocol combining beadbeating and hot-acid-phenol was developed in order to maximize bacterial mRNA yields and quality following total RNA extraction from lung lesions. Nearly all <it>A. pleuropneumoniae </it>transcripts could be detected on our microarrays, and 150 genes were deemed differentially expressed <it>in vivo </it>during the acute phase of the infection. Our results indicate that, for example, gene <it>apxIVA </it>from an operon coding for RTX toxin ApxIV is highly up-regulated <it>in vivo</it>, and that two genes from the operon coding for type IV fimbriae (APL_0878 and APL_0879) were also up-regulated. These transcriptional profiling data, combined with previous comparative genomic hybridizations performed by our group, revealed that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and that 3 of them code for products that are predicted outer membrane proteins (genes <it>irp </it>and <it>APL_0959</it>, predicted to code for a TonB-dependent receptor and a filamentous hemagglutinin/adhesin respectively) or lipoproteins (gene <it>APL_0920</it>). Only 4 of 72 up-regulated genes had previously been identified in controled experimental infections.</p> <p>Conclusions</p> <p>These genes that we have identified as up-regulated in <it>vivo</it>, conserved across serotypes and coding for potential outer membrane proteins represent potential candidates for the development of a cross-protective vaccine against porcine pleuropneumonia.</p

Assessing Hafting Adhesive Efficiency in the Experimental Shooting of Projectile Points: A new Device for Instrumented and Ballistic Experiments

International audienceWith the aim of providing better control of shooting experiments performed with replicas of prehistoric projectiles, we have conducted an instrumental archaeology study on the efficiency of prehistoric projectile points by placing emphasis on their adhesion and ballistic characteristics. In order to avoid any reproducibility problems, hafting adhesives were made with controlled mixtures of commercial rosin (also called ‘colophany’) and beeswax added as a plasticizer. An original experimental device has been developed to instrument a bow, allowing the control of both the trajectories and the velocities of the different shoots. In the course of an experimental programme on Sauveterrian microliths from the Mesolithic period of the South of France, the experimental system was applied to composite replica projectile tips of Mesolithic hunters. Arrows being shot at transparent targets were filmed in order to evaluate the penetration length and residual damage. Interestingly, this study reveals that the properties of the mixture are highly dependent on the velocity of the arrows. It was shown that—contrary to previous experiments that usually used a mixture in which rosin predominates— the most efficient adhesive is made of 70 wt% beeswax with only 30 wt% rosin. This result is of great importance for improving further shooting experiments and overcoming the problems frequently mentioned due to the loss of the flint armatures before they reach the animal target, or at least before penetration. When using this appropriate mixture, the lateral armatures are resistant to most of the shots. Experiments performed on real boars’ flesh have also shown that the presence of lateral microliths allows the laceration inflicted on the target to be enlarged. Finally, a critical parameter has been identified, which is the location on the arrow of the microlithic element

Efficacy of First-Line Chemotherapy in Patients with Advanced Lung Sarcomatoid Carcinoma

Background:Sarcomatoid carcinomas (SCs) are rare tumors that may arise in the lung, accounting for 0.4% of non–small-cell lung cancers; the prognosis is poor. Only few retrospective small-size series have studied the efficacy of chemotherapy (CT) for metastatic SC.Methods:Multicenter study of patients with advanced or metastatic SC who received first-line CT. Clinical characteristics at baseline, response to first-line CT (Response Evaluation Criteria in Solid Tumors version 1.1), progression-free survival (PFS), and overall survival (OS) were retrospectively collected.Results:Ninety-seven patients were included. Median age was 62 (54–72) years. The majority of patients were men (70%), white (84%), and smokers (84%). Overall, 73% of patients received first-line platinum-based CT. At first tumor evaluation, 69% of patients experienced progression, 31% had disease control, and 16.5% had partial response. Partial response was observed in 20% of patients receiving platinum-based CT, and in none of those receiving non–platinum-based CT (p = 0.018). Median PFS was 2.0 months (confidence interval [CI] 95%: 1.8–2.3). PFS was not statistically different between patients receiving or not receiving a platinum-based CT. Median OS was 6.3 months (CI 95%: 4.7–7.8). There was a trend toward better OS for patients treated with platinum-based CT (7.0 months [CI 95%: 4.9–9.0] versus 5.3 months [CI 95%: 2.8–7.6]; p = 0.096). In multivariate analysis, disease control at first evaluation (hazard ratio = 0.38 [CI 95%: 0.21–0.59]) and at platinum-based CT (hazard ratio = 0.92 [CI 95%: 0.85–0.99]) was associated with better OS.Conclusion:SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC

Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics

Despite numerous advances in the identification of the molecular machinery for clathrin-mediated budding at the plasma membrane, the mechanistic details of this process remain incomplete. Moreover, relatively little is known regarding the regulation of clathrin-mediated budding at other membrane systems. To address these issues, we have utilized the powerful new approach of subcellular proteomics to identify novel proteins present on highly enriched clathrin-coated vesicles (CCVs). Among the ten novel proteins identified is the rat homologue of a predicted gene product from human, mouse, and Drosophila genomics projects, which we named enthoprotin. Enthoprotin is highly enriched on CCVs isolated from rat brain and liver extracts. In cells, enthoprotin demonstrates a punctate staining pattern that is concentrated in a perinuclear compartment where it colocalizes with clathrin and the clathrin adaptor protein (AP)1. Enthoprotin interacts with the clathrin adaptors AP1 and with Golgi-localized, γ-ear–containing, Arf-binding protein 2. Through its COOH-terminal domain, enthoprotin binds to the terminal domain of the clathrin heavy chain and stimulates clathrin assembly. These data suggest a role for enthoprotin in clathrin-mediated budding on internal membranes. Our study reveals the utility of proteomics in the identification of novel vesicle trafficking proteins

Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects.

Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer