Instantons and framed sheaves on Kähler Deligne–Mumford stacks

We provide stacky generalizations of classical gauge-theoretic results inspired by Donaldson, the Uhlenbeck-Yau theorem and variants due to Bando and his collaborators. Moreover, we show an application of this machinery in the study of ALE spaces. Content

A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (γ-glutamyl transpeptidase, alanine aminotransferase, α(2)-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When γ-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of γ-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of γ-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and γ-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed

An Alternate, Egg-Free Radiolabeled Meal Formulation for Gastric-Emptying Scintigraphy

International audienceIn recent years, inherited and acquired mutations in the tricarboxylic acid (TCA) cycle enzymes have been reported in diverse cancers. Pheochromocytomas and paragangliomas often exhibit dysregulation of glucose metabolism, which is also driven by mutations in genes encoding the TCA cycle enzymes or by activation of hypoxia signaling. Pheochromocytomas and paragangliomas associated with succinate dehydrogenase (SDH) deficiency are characterized by high 18F-FDG avidity. This association is currently only partially explained. Therefore, we hypothesized that accumulation of succinate due to the TCA cycle defect could be the major connecting hub between SDH-mutated tumors and the 18F-FDG uptake profile. Methods: To test whether succinate modifies the 18F-FDG metabolic profile of tumors, we performed in vitro and in vivo (small-animal PET/CT imaging and autoradiography) experiments in the presence of succinate, fumarate, and phosphate-buffered saline (PBS) in different cell models. As a control, we also evaluated the impact of succinate on 18F-fluorocholine uptake and retention. Glucose transporter 1 (GLUT1) immunohistochemistry was performed to assess whether 18F-FDG uptake correlates with GLUT1 staining. Results: Intratumoral injection of succinate significantly increased 18F-FDG uptake at 24 h on small-animal PET/CT imaging and autoradiography. No effect of succinate was observed on cancer cells in vitro, but interestingly, we found that succinate caused increased 18F-FDG uptake by human umbilical vein endothelial cells in a concentration-dependent manner. No significant effect was observed after intratumoral injection of fumarate or PBS. Succinate, fumarate, and PBS have no effect on cell viability, regardless of cell lineage. Intramuscular injection of succinate also significantly increases 18F-FDG uptake by muscle when compared with either PBS or fumarate, highlighting the effect of succinate on connective tissues. No difference was observed between PBS and succinate on 18F-fluorocholine uptake in the tumor and muscle and on hind limb blood flow. GLUT1 expression quantification did not significantly differ between the study groups. Conclusion: The present study shows that succinate stimulates 18F-FDG uptake by endothelial cells, a finding that partially explains the 18F-FDG metabotype observed in tumors with SDH deficiency. Although this study is an 18F-FDG-based approach, it provides an impetus to better characterize the determinants of 18F-FDG uptake in various tumors and their surrounding microenvironment, with a special emphasis on the role of tumor-specific oncometabolites

Spectral network based on component cells under the SOPHIA European project

In the frame of the European project SOPHIA, a spectral network based on component (also called isotypes) cells has been created. Among the members of this project, several spectral sensors based on component cells and collimating tubes, so-called spectroheliometers, were installed in the last years, allowing the collection of minute-resolution spectral data useful for CPV systems characterization across Europe. The use of spectroheliometers has been proved useful to establish the necessary spectral conditions to perform power rating of CPV modules and systems. If enough data in a given period of time is collected, ideally a year, it is possible to characterize spectrally the place where measurements are taken, in the same way that hours of annual irradiation can be estimated using a pyrheliometer

Lansoprazole is an antituberculous prodrug targeting cytochrome bc1

Better antibiotics capable of killing multi-drug-resistant Mycobacterium tuberculosis are urgently needed. Despite extensive drug discovery efforts, only a few promising candidates are on the horizon and alternative screening protocols are required. Here, by testing a panel of FDA-approved drugs in a host cell-based assay, we show that the blockbuster drug lansoprazole (Prevacid), a gastric proton-pump inhibitor, has intracellular activity against M. tuberculosis. Ex vivo pharmacokinetics and target identification studies reveal that lansoprazole kills M. tuberculosis by targeting its cytochrome bc(1) complex through intracellular sulfoxide reduction to lansoprazole sulfide. This novel class of cytochrome bc(1) inhibitors is highly active against drug-resistant clinical isolates and spares the human H+K+-ATPase thus providing excellent opportunities for targeting the major pathogen M. tuberculosis. Our finding provides proof of concept for hit expansion by metabolic activation, a powerful tool for antibiotic screens

Characterisation of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicronaemia syndrome (MCS): establishment of an FCS clinical diagnostic score

Data presented in this article are supplementary material to our article entitled "Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recom mendations and proposal of an "FCS Score" (Moulin et al., 2018, in press). The data describe the genotypes of patients with familial chylomicronaemia syndrome (FCS) and multifactorial chylomicro naemia syndrome (MCS), from the validation and replication cohorts

Real-Time Microbiology Laboratory Surveillance System to Detect Abnormal Events and Emerging Infections, Marseille, France

International audienceInfectious diseases are a major threat to humanity, and accurate surveillance is essential. We describe how to implement a laboratory data–based surveillance system in a clinical microbiology laboratory. Two historical Microsoft Excel databases were implemented. The data were then sorted and used to execute the following 2 surveillance systems in Excel: the Bacterial real-time Laboratory-based Surveillance System (BALYSES) for monitoring the number of patients infected with bacterial species isolated at least once in our laboratory during the study periodl and the Marseille Antibiotic Resistance Surveillance System (MARSS), which surveys the primary β-lactam resistance phenotypes for 15 selected bacterial species. The first historical database contained 174,853 identifications of bacteria, and the second contained 12,062 results of antibiotic susceptibility testing. From May 21, 2013, through June 4, 2014, BALYSES and MARSS enabled the detection of 52 abnormal events for 24 bacterial species, leading to 19 official reports. This system is currently being refined and improved

Rain-Use-Efficiency: What it Tells us about the Conflicting Sahel Greening and Sahelian Paradox

Rain Use Efficiency (RUE), defined as Aboveground Net Primary Production (ANPP) divided by rainfall, is increasingly used to diagnose land degradation. Yet, the outcome of RUE monitoring has been much debated since opposite results were found about land degradation in the Sahel region. The debate is fueled by methodological issues, especially when using satellite remote sensing data to estimate ANPP, and by differences in the ecological interpretation. An alternative method which solves part of these issues relies on the residuals of ANPP regressed against rainfall (“ANPP residuals”). In this paper, we use long-term field observations of herbaceous vegetation mass collected in the Gourma region in Mali together with remote sensing data (GIMMS-3g Normalized Difference Vegetation Index) to estimate ANPP, RUE, and the ANPP residuals, over the period 1984–2010. The residuals as well as RUE do not reveal any trend over time over the Gourma region, implying that vegetation is resilient over that period, when data are aggregated at the Gourma scale. We find no conflict between field-derived and satellite-derived results in terms of trends. The nature (linearity) of the ANPP/rainfall relationship is investigated and is found to have no impact on the RUE and residuals interpretation. However, at odds with a stable RUE, an increased run-off coefficient has been observed in the area over the same period, pointing towards land degradation. The divergence of these two indicators of ecosystem resilience (stable RUE) and land degradation (increasing run-off coefficient) is referred to as the “second Sahelian paradox”. When shallow soils and deep soils are examined separately, high resilience is diagnosed on the deep soil sites. However, some of the shallow soils show signs of degradation, being characterized by decreasing vegetation cover and increasing run-off coefficient. Such results show that contrasted changes may co-exist within a region where a strong overall re-greening pattern is observed, highlighting that both the scale of observations and the scale of the processes have to be considered when performing assessments of vegetation changes and land degradation