Estimating the exchanged energy distribution in micro-EDM

This paper presents a new approach for the recording of the total quantity of energy exchanged during the micro Electro Discharge Machining (EDM) process. In particular, this approach allows for the estimation of the percentage of energy absorbed by the two electrodes (tool and workpiece) using a combination of theoretical models and experimental results, thanks to an advanced discharges measuring approach. The validity of several theoretical crater models was then assessed. Using this approach, the process was analysed for two electrode shapes and two sets of machining parameters. The preliminary results appears to fit those presented in the literature

Estimating the exchanged energy distribution in micro-EDM

This paper presents a new approach for the recording of the total quantity of energy exchanged during the micro Electro Discharge Machining (EDM) process. In particular, this approach allows for the estimation of the percentage of energy absorbed by the two electrodes (tool and workpiece) using a combination of theoretical models and experimental results, thanks to an advanced discharges measuring approach. The validity of several theoretical crater models was then assessed. Using this approach, the process was analysed for two electrode shapes and two sets of machining parameters. The preliminary results appears to fit those presented in the literature

Estimating the exchanged energy distribution in micro-EDM

International audienceThis paper presents a new approach for the recording of the total quantity of energy exchanged during the micro Electro Discharge Machining (EDM) process. In particular, this approach allows for the estimation of the percentage of energy absorbed by the two electrodes (tool and workpiece) using a combination of theoretical models and experimental results, thanks to an advanced discharges measuring approach. The validity of several theoretical crater models was then assessed. Using this approach, the process was analysed for two electrode shapes and two sets of machining parameters. The preliminary results appears to fit those presented in the literature

Hypoxic culture conditions enhance the generation of regulatory T cells

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Using a multi-criteria decision-matrix framework to assess the recovery potential of coral reefs in the South Western Indian Ocean

Over the last two decades, coral reefs have experienced dire declines due to intensifying anthropogenic disturbances and climate change. Defining and quantifying coral reef resilience now represents a critical management objective, but there is still little consensus on the approach and the indices to be used. In this study, we develop a multi-factor reef recovery index based on the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method to assess the vulnerability of several insular coral reefs in the South Western Indian Ocean (SWIO) from 2016 to 2018. We showed, that in the wake of a regional bleaching event in 2016, the most isolated reefs of Europa, which is characterized by low direct human impact had the highest recovery potential. On the contrary, islands that are more prone to direct human influence (i.e., La Reunion and Rodrigues) displayed the lowest recovery potential

Using a multi-criteria decision-matrix framework to assess the recovery potential of coral reefs in the South Western Indian Ocean

Over the last two decades, coral reefs have experienced dire declines due to intensifying anthropogenic disturbances and climate change. Defining and quantifying coral reef resilience now represents a critical management objective, but there is still little consensus on the approach and the indices to be used. In this study, we develop a multi-factor reef recovery index based on the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) method to assess the vulnerability of several insular coral reefs in the South Western Indian Ocean (SWIO) from 2016 to 2018. We showed, that in the wake of a regional bleaching event in 2016, the most isolated reefs of Europa, which is characterized by low direct human impact had the highest recovery potential. On the contrary, islands that are more prone to direct human influence (i.e., La Reunion and Rodrigues) displayed the lowest recovery potential

Aortic valve calcification is promoted by interleukin-8 and restricted through antagonizing CXCR2

International audienceAims Inflammatory cytokines play a critical role in the progression of calcific aortic valve disease (CAVD), for which there is currently no pharmacological treatment. The aim of this study was to test the hypothesis that interleukin-8 (IL-8), known to be involved in arterial calcification, also promotes aortic valve calcification (AVC) and to evaluate whether pharmacologically blocking the IL-8 receptor, CXC motif chemokine receptor 2 (CXCR2), could be effective in preventing AVC progression. Methods and Results A cohort of 195 patients (median age 73, 74% men) diagnosed with aortic valve stenosis (severe in 16.9% of cases) were prospectively followed by CT for a median time of 2.6 years. A Cox proportional hazards regression analysis indicated that baseline IL-8 serum concentrations were associated with rapid progression of AVC, defined as an annualized change in the calcification score by CT ≥ 110 AU/year, after adjustment for age, gender, bicuspid anatomy and baseline disease severity. In vitro, exposure of primary human aortic valvular interstitial cells (hVICs) to 15 pg/ml IL-8 induced a two-fold increase in inorganic phosphate (Pi)-induced calcification. IL-8 promoted NFκB pathway activation, MMP-12 expression, and elastin degradation in hVICs exposed to Pi. These effects were prevented by SCH527123, an antagonist of CXCR2. The expression of CXCR2 was confirmed in hVICs and samples of aortic valves isolated from patients with CAVD, in which the receptor was mainly found in calcified areas, along with MMP-12 and a degraded form of elastin. Finally, in a rat model of chronic kidney disease-associated CAVD, SCH527123 treatment (1 mg/kg/day given orally for 11 weeks) limited the decrease in aortic cusp separation, the increase in maximal velocity of the transaortic jet, and the increase in aortic mean pressure gradient measured by echocardiography, effects that were associated with a reduction in hydroxyapatite deposition and MMP-12 expression in the aortic valves. Conclusion Overall, these results highlight, for the first time, a significant role for IL-8 in the progression of CAVD by promoting calcification via a CXCR2­- and MMP-12-dependent mechanism that leads to elastin degradation, and identify CXCR2 as a promising therapeutic target for the treatment of CAVD

At the crossroads of fertility and metabolism: the importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism

International audienceStudy question: What biological processes are linked to the signaling of the energy sensor 5'-AMP-activated protein kinase (AMPK) in mouse and human granulosa cells (GCs)?Summary answer: The lack of α1AMPK in GCs impacted cell cycle, adhesion, lipid metabolism and induced a hyperandrogenic response.What is known already: AMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids. Polycystic ovary syndrome (PCOS) is responsible for infertility in approximately 5-20% of women of childbearing age and possible treatments include reducing body weight, improving lifestyle and the administration of a combination of drugs to improve insulin resistance, such as metformin.Study design, size, duration: AMPK signaling was evaluated by analyzing differential gene expression in immortalized human granulosa cells (KGNs) with and without silencing α1AMPK using CRISPR/Cas9. In vivo studies included the use of a α1AMPK knock-out mouse model to evaluate the role of α1AMPK in folliculogenesis and fertility. Expression of α1AMPK was evaluated in primary human granulosa-luteal cells retrieved from women undergoing IVF with and without a lean PCOS phenotype (i.e. BMI: 18-25 kg/m2).Participants/materials, setting, methods: α1AMPK was disrupted in KGN cells and a transgenic mouse model. Cell viability, proliferation and metabolism were evaluated. Androgen production was evaluated by analyzing protein levels of relevant enzymes in the steroid pathway by western blots, and steroid levels obtained from in vitro and in vivo models by mass spectrometry. Differential gene expression in human GC was obtained by RNA sequencing. Analysis of in vivo murine folliculogenesis was performed by histology and immunochemistry, including evaluation of the anti-Müllerian hormone (AMH) marker. The α1AMPK gene expression was evaluated by quantitative RT-PCR in primary GCs obtained from women with the lean PCOS phenotype (n = 8) and without PCOS (n = 9).Main results and the role of chance: Silencing of α1AMPK in KGN increased cell proliferation (P < 0.05 versus control, n = 4), promoted the use of fatty acids over glucose, and induced a hyperandrogenic response resulting from upregulation of two of the enzymes involved in steroid production, namely 3β-hydroxysteroid dehydrogenase (3βHSD) and P450 side-chain cleavage enzyme (P450scc) (P < 0.05, n = 3). Female mice deficient in α1AMPK had a 30% decrease in their ovulation rate (P < 0.05, n = 7) and litter size, a hyperandrogenic response (P < 0.05, n = 7) with higher levels of 3βHSD and p450scc levels in the ovaries, and an increase in the population of antral follicles (P < 0.01, n = 10) compared to controls. Primary GCs from lean women with PCOS had lower α1AMPK mRNA expression levels than the control group (P < 0.05, n = 8-9).Large scale data: The FastQ files and metadata were submitted to the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB46048.Limitations, reasons for caution: The human KGN is a not fully differentiated, transformed cell line. As such, to confirm the role of AMPK in GC and the PCOS phenotype, this model was compared to two others: an α1AMPK transgenic mouse model and primary differentiated granulosa-lutein cells from non-obese women undergoing IVF (with and without PCOS). A clear limitation is the small number of patients with PCOS utilized in this study and that the collection of human GCs was performed after hormonal stimulation.Wider implications of the findings: Our results reveal that AMPK is directly involved in steroid production in human GCs. In addition, AMPK signaling was associated with other processes frequently reported as dysfunctional in PCOS models, such as cell adhesion, lipid metabolism and inflammation. Silencing of α1AMPK in KGN promoted folliculogenesis, with increases in AMH. Evaluating the expression of the α1AMPK subunit could be considered as a marker of interest in infertility cases related to hormonal imbalances and metabolic disorders, including PCOS.Study funding/competing interest(s): This study was financially supported by the Institut National de la Recherche Agronomique (INRA) and the national programme « FERTiNERGY » funded by the French National Research Agency (ANR). The authors report no intellectual or financial conflicts of interest related to this work. R.K. is identified as personnel of the International Agency for Research on Cancer/World Health Organization. R.K. alone is responsible for the views expressed in this article and she does not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.Trial registration number: N/A

Does awake prone positioning prevent the use of mechanical respiratory support or death in COVID-19 patients on standard oxygen therapy hospitalised in general wards? A multicentre randomised controlled trial: the PROVID-19 protocol

Introduction COVID-19 is responsible of severe hypoxaemia and acute respiratory distress syndrome (ARDS). Prone positioning improves oxygenation and survival in sedated mechanically patients with ARDS not related to COVID-19. Awake prone positioning is a simple and safe technique which improves oxygenation in non-intubated COVID-19 patients. We hypothesised that early prone positioning in COVID-19 patients breathing spontaneously in medical wards could decrease the rates of intubation or need for noninvasive ventilation or death.Methods and analysis PROVID-19 is an investigator-initiated, prospective, multicentre randomised, controlled, superiority trial comparing awake prone positioning to standard of care in hypoxaemic COVID-19 patients in 20 medical wards in France and Monaco. Patients are randomised to receive either awake prone position plus usual care or usual care alone with stratification on centres, body mass index and severity of hypoxaemia.The study objective is to compare the rate of treatment failure defined as a composite endpoint comprising the need for non-invasive ventilation (at two pressure levels) or for intubation or death, between the intervention group (awake prone position plus usual care) and the usual care (usual care alone) group at 28 days.Ethics and dissemination The protocol and amendments have been approved by the ethics committees (Comité de protection des personnes Ouest VI, France, no 1279 HPS2 and Comité Consultatif d’Ethique en matière de Recherche Biomédicale, Monaco, no 2020.8894 AP/jv), and patients are included after written informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT04363463

Gut bacteria Akkermansia elicit a specific IgG response in CSF of patients with MS

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