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Processing of Russian olive water kefir (RWK), as a fermented functional drink made with Russian olive juice and water kefir grains with high antioxidant activity, into powder is crucial for improving its stability for the commercialization of this product. For the first time, this study aimed to encapsulate water kefir microorganisms and bioactive compounds in RWK using carrier materials to develop a synbiotic functional powder using spray drying as an encapsulation method. The goal was maximizing antioxidant activity, product yield, and survival rate of water kefir microorganisms in the produced Russian olive water kefir powder. The optimal spray drying conditions were observed to be at an inlet air temperature of 120ºC, 35 % feed flow rate, and 7 % concentration of drying aid. The effects of spray drying conditions on the quality of microcapsules were assessed and modeled, and the validity of the model was verified. Also, the spray-dried powder's physicochemical properties were assessed and showed promising microbial and physicochemical characteristics compared with the freeze-dried powder.

Although the structure and properties of water under conditions of extreme confinement are fundamentally important for a variety of applications, they remain poorly understood, especially for dimensions less than 2 nm. This problem is confounded by the difficulty in controlling surface roughness and dimensionality in fabricated nanochannels, contributing to a dearth of experimental platforms capable of carrying out the necessary precision measurements. In this work, we utilize an experimental platform based on the interior of lithographically segmented, isolated single-walled carbon nanotubes to study water under extreme nanoscale confinement. This platform generates multiple copies of nanotubes with identical chirality, of diameters from 0.8 to 2.5 nm and lengths spanning 6 to 160 μm, that can be studied individually in real time before and after opening, exposure to water, and subsequent water filling. We demonstrate that, under controlled conditions, the diameter-dependent blue shift of the Raman radial breathing mode (RBM) between 1 and 8 cm

Serine hydrolases comprise a large family of enzymes that have diverse roles in key cellular processes, such as lipid metabolism, cell signaling, and regulation of post-translation modifications of proteins. They are also therapeutic targets for multiple human pathologies, including viral infection, diabetes, hypertension, and Alzheimer disease; however, few have well-defined substrates and biological functions. Activity-based probes (ABPs) have been used as effective tools to both profile activity and screen for selective inhibitors of serine hydrolases. One broad-spectrum ABP containing a fluorophosphonate electrophile has been used extensively to advance our understanding of diverse serine hydrolases. Due to the success of this single reagent, several robust chemistries have been developed to further diversify and tune the selectivity of ABPs used to target serine hydrolases. In this review, we highlight approaches to identify selective serine hydrolase ABPs and suggest new synthetic methodologies that could be applied to further advance probe development.

Cranberry juice is increasingly consumed for its richness in polyphenols having a positive impact on human health. Unfortunately, when regularly consumed, its high concentration in organic acids may cause some intestinal discomforts. In the present study, its organic acid content was reduced of 41% by electrodialysis with bipolar membrane (EDBM), and the resulted deacidified juice was divided in five different juices readjusted or not with different concentrations of citric and/or malic acid(s) corresponding to the concentration of this/these acid(s) recovered during EDBM or at the titratable acidity (TA) of the non-deacidified cranberry juice. The evolution of the cranberry juice main interesting compounds (organic acids and polyphenols), according to the concentration and nature of the organic acids present, was studied for the first time at each specific stages of the digestion. After digestion, Caco-2 cells were exposed to all digested juices to identify the organic acid(s) responsible for the loss of integrity of the epithelial barrier. It appeared that organic acid contents did not change during the different steps of the digestion while polyphenolic compounds decreased starting from the gastric phase. Whatever the organic acid concentration or nature, the concentration of PACs significantly decreased between the salivary and the gastric steps but was different according to their structure when the concentration of most of anthocyanins significantly decreased at the gastric step. Also, to the best of our knowledge, it was the first time that citric acid was demonstrated as the organic acid responsible for the loss of integrity of Caco-2 cell monolayers.

Background Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. Objectives We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Methods Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. Results We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC. Conclusions In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.

Transition metals are toxic at high concentrations. The P1B-ATPase metal exporter CtpC/Rv3270 is required for resistance to zinc poisoning in the human pathogen Mycobacterium tuberculosis. Here, we discovered that zinc resistance also depends on the chaperone-like protein PacL1/Rv3269. PacL1 bound Zn2+, but unlike PacL1 and CtpC, the PacL1 metal-binding motif (MBM) was required only at high zinc concentrations. PacL1 co-localized with CtpC in dynamic microdomains within the mycobacterial plasma membrane. Microdomain formation did not require flotillins nor the PacL1 MBM. Instead, loss of the PacL1 Glutamine/Alanine repeats led to loss of CtpC and sensitivity to zinc. PacL1 and CtpC are within the same operon, and homologous PacL1-P1B-ATPase pairs are widely distributed within and across prokaryotes. PacL1 colocalized and functioned redundantly with PacL orthologs in Mycobacterium tuberculosis. Overall, our study suggests that PacL proteins are scaffolds that assemble P-ATPase-containing metal efflux platforms, a novel type of functional membrane microdomain that underlies bacterial resistance to metal poisoning.

International audience; In this communication we present the development of a travelling wave photoconductor for THz generation by photomixing. It is based on a silicon nitride optical waveguide coupled to a membrane-supported low-temperature-grown GaAs photoconductor embedded in a coplanar waveguide. The frequency response of a 1-mm-long structure, measured up to 100 GHz by using the beatnote produced by two 780-nm-DFB lasers, shows the expected travelling wave signature consisting in a 6-dB-decrease ending at ~50 GHz when the contribution of the backward travelling wave is fully cancelled, following by a constant level up to ~100 GHz.

Tacrolimus, prescribed to a majority of transplanted patients is associated with nephrotoxicity, the mechanism of which remains unclear. This study aims to evaluate the impact of tacrolimus on proximal tubular cells using a multi-omics approach. LLC-PK1 cells were exposed to 5 {micro}M of tacrolimus for 24h. Intracellular proteins and metabolites, and extracellular metabolites were extracted and analysed by LC-MS/MS. The transcriptional expression of PCK-1, FBP1 and FBP2 was measured using RT-qPCR. In our cell model, tacrolimus impacted different metabolic pathways including urea cycle (e.g., citrulline, ornithine) (p < 0.0001), amino acid metabolism (e.g., valine, isoleucine, aspartic acid) (p < 0.0001) and pyrimidine metabolism (p

We demonstrate 1.7–18 µm mid-infrared coherent supercontinuum generation by means of the full transmission window of a unique dispersion-engineered step-index Ge-Se-Te fiber. Our study thus opens the entire molecular fingerprint region to future chalcogenide fiber platforms.

International audience; We experimentally and theoretically investigate the field-free alignment of the asymmetric-top acetone molecule. Our study shows that the production of postpulse aligned molecules in a dense sample (0.05-0.2 bar) of room-temperature acetone using a single-pulse excitation can be significantly improved by rotational alignment echoes induced in a two-pulse excitation scheme. We report the observation of fractional echoes that can be used to reveal the nonlinearity of the molecular system. In a proof-of-principle experiment, a pre-aligned sample of acetone is also used for third-harmonic generation. The analysis of the experimental data with numerical simulations based on quantum and classical models enables the determination of the collisional decay rate of acetone alignment, as well as a test of the static, second-order, electric hyperpolarizabilities of the molecule derived from ab initio calculations presented in this work.

Museums are perfect experimentation grounds for indoor positioning technologies. Indeed, museum managers are always pleased to hold these kinds of events where it offers the opportunity to the public to be a part of such experimentation and allowing us at the same time to popularize our research with them. In this paper, we describe an experiment that held within the museum of natural history of La Rochelle with a class of high school volunteers. We will explain our systems that has been built to work in this specific case, and among other things formalize our algorithm for indoor localization that has not had an equivalent in the state of the art. The minimal zone searching algorithm (MZS) can compute in real time the position of a visitor, shaped as a zone with an average surface of 3 m2 when resources are limited and when the placement of nodes must respect the constraints imposed by the room’s layout. This method offered good results with data collected during the experimentation, such as a meaningful representation of the position of a visitor and most importantly a stable execution during the whole experience even when the subject was in tight spaces.

Calcineurin inhibitors (CNI) are the pillars of immunosuppression in transplantation. However, they display a potent nephrotoxicity whose mechanisms remained widely unsolved. We used an untargeted quantitative proteomic approach (iTRAQ technology) to highlight new targets of CNI in renal proximal tubular cells (RPTCs). CNI‐treated RPTCs proteome displayed an over‐representation of actin‐binding proteins with a CNI‐specific expression profile. Cyclosporine A (CsA) induced F‐actin remodeling and depolymerization, decreased F‐actin‐stabilizing, polymerization‐promoting cofilin (CFL) oligomers, and inhibited the G‐actin‐regulated serum response factor (SRF) pathway. Inhibition of CFL canonical phosphorylation pathway reproduced CsA effects; however, S3‐R, an analogue of the phosphorylation site of CFL prevented the effects of CsA which suggests that CsA acted independently from the canonical CFL regulation. CFL is known to be regulated by the Na+/K+‐ATPase. Molecular docking calculations identified two inhibiting sites of CsA on Na+/K+‐ATPase and a 23% decrease in Na+/K+‐ATPase activity of RPTCs was observed with CsA. Ouabain, a specific inhibitor of Na+/K+‐ATPase also reproduced CsA effects on actin organization and SRF activity. Altogether, these results described a new original pathway explaining CsA nephrotoxicity.

RIP1 kinase regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including inflammatory and neurological diseases. Currently, RIP1 kinase inhibitors have advanced into early clinical trials for evaluation in inflammatory diseases such as psoriasis, rheumatoid arthritis, and ulcerative colitis and neurological diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. In this paper, we report on the design of potent and highly selective dihydropyrazole (DHP) RIP1 kinase inhibitors starting from a high-throughput screen and the lead-optimization of this series from a lead with minimal rat oral exposure to the identification of dihydropyrazole 77 with good pharmacokinetic profiles in multiple species. Additionally, we identified a potent murine RIP1 kinase inhibitor 76 as a valuable in vivo tool molecule suitable for evaluating the role of RIP1 kinase in chronic models of disease. DHP 76 showed efficacy in mouse models of both multiple sclerosis and human retinitis pigmentosa.

International audience; In the present work, major and trace element concentrations in suspensions of volcanic ash nanoparticles were determined by ICP-MS after either the acid digestion of the suspensions or the direct analysis of these suspensions. The results obtained were compared. Since the acid digestion can be accompanied by an important dilution or can consist in different steps of evaporation and dilution, the determination of some trace element concentrations became limited because of the limit of detection of the analytical instrument. Therefore, analysis after acid digestion of suspensions and direct analysis after acidification of these suspensions were carried out and compared. The concentration of Al, Fe, Y, La, Ce, Pr, Gd, Ho, Cu, Tl and Pb determined by both preparation procedures were in agreement. The values of relative standard deviation are in the range from 1% to 14%. These results prove the reliability of the direct ICP-MS analysis and the possibility of its further application in hyphenated systems for the dimensional and elemental characterisation of natural mineral nanoparticles

The intracellular pathogen Legionella pneumophila (Lp) is a strict aerobe, surviving and replicating in environments where it frequently encounters reactive oxygen species (ROS), such as the nutrient-poor water environment and its replicative niche inside host cells. In many proteobacteria, the LysR-type regulator OxyR controls the oxidative stress response; however, the importance of the OxyR homologue in Lp is still unclear. Therefore, we undertook the characterization of phenotypes associated with the deletion of oxyR in Lp. Contrary to the wild type, the oxyR deletion mutant exhibits a severe growth defect on charcoal – yeast extract (CYE) agar lacking α-ketoglutarate supplementation. Growth in AYE broth (CYE without agar and charcoal), in amoeba and in human cultured macrophages, and survival in water is unaffected by the deletion. Supplementing CYE agar with antioxidants that neutralize ROS or introducing the oxyR gene in trans rescues the observed growth defect. Moreover, the mutant grows as well as the wild type on CYE plates made with agarose instead of agar, suggesting that a compound present in the latter is responsible for the growth defect phenotype.

International audience; Platinum group elements (PGE: Ru, Rh, Pd, Os Ir, Pt) are rare metals with low abundance in the continental crust. The elements of the palladium subgroup of PGE (PPGE: Pt, Pd, Rh) have been exploited more and more over the last thirty years for their physicochemical properties such as high melting point, high resistance to corrosion, mechanical strength and ductility. This led to emerging environmental contamination in different media such as air, road dust, soil, sediment, vegetation, and snow. The aim of this review is to summarize the available data on soil contamination by PPGE and its potential environmental impact. In this paper, the environmental issue of PPGE is discussed with regard to their anthropogenic emission and fate, which includes speciation, possible transformations into bioavailable forms and toxicity. Soil contamination by PPGE is described taking into account urban and non-urban areas. The analytical determination process is also discussed.

International audience; The objective of this work was to explore centrifugal ultrafiltration (UF) to separate and / or preconcentrate natural colloidal particles for their characterization. A soil suspension obtained by batch leaching was used as a laboratory reference sample. It was preconcentrated with concentration factors (CF) varying from 10 to 450. The dimensional analysis of the colloidal phase was carried out by Asymmetric Flow Field-Flow Fractionation (AF4)-multidetection. The colloidal masses were estimated by mass balance of the initial suspension, its concentrates and filtrates. The size-dependent distribution (expressed in gyration radius) and total colloidal mass (especially recovery), as well as chemical composition and concentration (including species partitioning between dissolved and colloidal phases) were determined to assess the effects of UF preconcentration on colloidal particles. The gyration radius of the colloidal particles recovered in these concentrated suspensions ranged from about 20 nm to over 150 nm. Neither de-agglomeration nor agglomeration was observed. However, only (64 ± 4) % (CF = 10) of the colloidal particles initially in the soil suspension were found in the recovered concentrated suspensions, and this percentage decreased as CF increased. The filter membrane trapped all other particles, mainly the larger ones. Whatever the CF, the centrifugal UF did not appear to change the dissolved-colloidal partitioning of certain species (Al, organic carbon); whereas it led to an enrichment of the colloidal phase for others (Fe, U). The enrichment rate was specific to each species (15% for Fe; 100% for U). By fitting the observed trends (i.e. conservation, depletion or enrichment of the colloidal phase in the concentrate) as a function of CF, the colloidal concentrations (total and species) were assessed without bias. This methodology offers a new perspective for determining physicochemical speciation in natural waters, with a methodology applicable for environmental survey or site remediation studies.

Objectives The aim of this study was to develop an algorithm capable of predicting short- and medium-term survival in cases of intrinsic acute-on-chronic kidney disease (ACKD) in cats. Methods The medical record database was searched to identify cats hospitalised for acute clinical signs and azotaemia of at least 48 h duration and diagnosed to have underlying chronic kidney disease based on ultrasonographic renal abnormalities or previously documented azotaemia. Cases with postrenal azotaemia, exposure to nephrotoxicants, feline infectious peritonitis or neoplasia were excluded. Clinical variables were combined in a clinical severity score (CSS). Clinicopathological and ultrasonographic variables were also collected. The following variables were tested as inputs in a machine learning system: age, body weight (BW), CSS, identification of small kidneys or nephroliths by ultrasonography, serum creatinine at 48 h (Crea48), spontaneous feeding at 48 h (SpF48) and aetiology. Outputs were outcomes at 7, 30, 90 and 180 days. The machine-learning system was trained to develop decision tree algorithms capable of predicting outputs from inputs. Finally, the diagnostic performance of the algorithms was calculated. Results Crea48 was the best predictor of survival at 7 days (threshold 1043 µmol/l, sensitivity 0.96, specificity 0.53), 30 days (threshold 566 µmol/l, sensitivity 0.70, specificity 0.89) and 90 days (threshold 566 µmol/l, sensitivity 0.76, specificity 0.80), with fewer cats still alive when their Crea48 was above these thresholds. A short decision tree, including age and Crea48, predicted the 180-day outcome best. When Crea48 was excluded from the analysis, the generated decision trees included CSS, age, BW, SpF48 and identification of small kidneys with an overall diagnostic performance similar to that using Crea48. Conclusions and relevance Crea48 helps predict short- and medium-term survival in cats with ACKD. Secondary variables that helped predict outcomes were age, CSS, BW, SpF48 and identification of small kidneys.

In large-building water systems, Legionella pneumophila is exposed to common environmental stressors such as copper. The aim of this study was to evaluate the susceptibility to copper of L. pneumophila isolates recovered from various sites: two clinical and seven environmental isolates from hot water system biofilm and water and from cooling tower water. After a 1-week acclimation in simulated drinking water, strains were exposed to various copper concentrations (0.8 to 5 mg/liter) for over 672 h. Complete loss of culturability was observed for three isolates following copper exposure to 5 mg/liter for 672 h. Two sequence type 1427 (ST1427)-like isolates were highly sensitive to copper, while the other two, isolated from biofilm samples, maintained higher culturability. The expression of the copper resistance gene copA evaluated by reverse transcription-quantitative PCR (RT-qPCR) was significantly higher for the biofilm isolates. All four ST1427-like isolates were recovered from the same water system during an outbreak. Whole-genome sequencing results confirmed that the four isolates are very close phylogenetically, differing by only 29 single nucleotide polymorphisms, suggesting in situ adaptation to microenvironmental conditions, possibly due to epigenetic regulation. These results indicate that the immediate environment within a building water distribution system influences the tolerance of L. pneumophila to copper. Increased contact of L. pneumophila biofilm strains with copper piping or copper alloys in the heat exchanger might lead to local adaptation. The phenotypic differences observed between water and biofilm isolates from the hot water system of a health care facility warrants further investigation to assess the relevance of evaluating disinfection performances based on water sampling alone. IMPORTANCELegionella pneumophila is a pathogen indigenous to natural and large building water systems in the bulk and the biofilm phases. The immediate environment within a system can impact the tolerance of L. pneumophila to environmental stressors, including copper. In health care facilities, copper levels in water can vary, depending on water quality, plumbing materials, and age. This study evaluated the impact of the isolation site (water versus biofilm, hot water system versus cooling tower) within building water systems. Closely related strains isolated from a health care facility hot water system exhibited variable tolerance to copper stress, shown by differential expression of copA, with biofilm isolates displaying highest expression and tolerance. Relying on the detection of L. pneumophila in water samples following exposure to environmental stressors such as copper may underestimate the prevalence of L. pneumophila, leading to inappropriate risk management strategies and increasing the risk of exposure for vulnerable patients.

Aptamers can serve as efficient bioreceptors for the development of biosensing detection platforms. Aptamers are short DNA or RNA oligonucleotides that fold into specific structures, which enable them to selectively bind to target analytes. The method used to identify aptamers is Systematic Evolution of Ligands through Exponential Enrichment (SELEX). Target properties can have an impact on aptamer efficiencies. Therefore, characteristics of water-borne microbial targets must be carefully considered during SELEX for optimal aptamer development. Several aptamers have been described for key water-borne pathogens. Here, we provide an exhaustive overview of these aptamers and discuss important microbial aspects to consider when developing such aptamers.

Mitochondria is often considered as the common nexus of cardiac and cerebral dysfunction after cardiac arrest. Here, our goal was to determine whether the time course of cardiac and cerebral mitochondrial dysfunction is similar after shockable versus non-shockable cardiac arrest in rabbits. Anesthetized rabbits were submitted to 10 min of no-flow by ventricular fibrillation (VF group) or asphyxia (non-shockable group). They were euthanized at the end of the no-flow period or 30 min, 120 min, or 24 h after resuscitation for in vitro evaluation of oxygen consumption and calcium retention capacity. In the brain (cortex and hippocampus), moderate mitochondrial dysfunction was evidenced at the end of the no-flow period after both causes of cardiac arrest versus baseline. It partly recovered at 30 and 120 min after cardiac arrest, with lower calcium retention capacity and higher substrate-dependant oxygen consumption after VF versus non-shockable cardiac arrest. However, after 24 h of follow-up, mitochondrial dysfunction dramatically increased after both VF and non-shockable cardiac arrest, despite greater neurological dysfunction after the latter one. In the heart, mitochondrial dysfunction was also maximal after 24 h following resuscitation, with no significant difference among the causes of the cardiac arrest. During the earlier timing of evaluation, calcium retention capacity and ADP-dependant oxygen consumption were lower and higher, respectively, after non-shockable cardiac arrest versus VF. In conclusion, the kinetics of cardiac and cerebral mitochondrial dysfunction suggests that mitochondrial function does not play a major role in the early phase of the post-resuscitation process but is only involved in the longer pathophysiological events.

Aim: Study of the biocidal effect of a cold atmospheric-pressure plasma in ambient air on single-species bacterial biofilms with controlled cell density, characterized by different extracellular matrices. Methods and results: Two bacterial strains were chosen to present different Gram properties and contrasted extracellular matrices: Pseudomonas aeruginosa ATCC 15442 (Gram-negative), and Leuconostoc citreum NRRL B-1299 (Gram-positive). P. aeruginosa biofilm exhibits a complex matrix, rich in proteins while L. citreum presents the specificity to produce glucan-type exopolysaccharides when grown in the presence of sucrose. Plasma was applied on both surface-spread cells and 24-h grown biofilms with controlled cell loads over 5, 10, or 20 min. Surface-spread bacteria showed a time dependent response, with a maximal bacterial reduction of 2.5 log after 20 min of treatment. On the other hand, in our experimental conditions, no bactericidal effect could be observed when treating biofilms of P. aeruginosa and glucan-rich L. citreum. Conclusions: For biofilms presenting equivalent cell loads, the response to plasma treatment seemed to depend on the properties of the extracellular matrix characterized by infrared spectroscopy, scanning electron microscopy, or dry weight. Significance and impact of study: Both cell load standardization and biofilm characterization are paramount factors to consider the biocide effect of plasma treatments. The extracellular matrix could affect the plasma efficacy by physical and/or chemical protective effects.

International audience; Dimensional and elemental characterization of environmental nanoparticles is a challenging task that requires the use of a set of complementary analytical methods. Asymmetric flow field-flow fractionation coupled with UV-Vis, multi-angle laser light scattering and ICP-MS detection was applied to study the nanoparticle fraction of a volcanic ash sample, in a Milli-Q water suspension at pH 6.8. It has been shown that the separated by sedimentation nanoparticle fraction of the Klyuchevskoy volcano ash suspension contains 3 polydisperse populations for which size ranges (expressed in gyration radius, rG), hydrodynamic behaviours (evaluated via shape index) and elemental compositions are different. These 3 populations did not dissolve over the 72-h study but aggregated and settled out differently. Thus, the population of particles with gyration radii

International audience; In this work, we provide an algorithm to compute efficiently and accurately the full outgoing modal Green's kernel for the scalar wave equation in local helioseismology under spherical symmetry. Due to the high computational cost of a full Green's function, current helioseismic studies rely on single-source computations. However, a more realistic modelization of the helioseismic products (cross-covariance and power spectrum) requires the full Green's kernel. In the classical approach, the Dirac source is discretized and one simulation gives the Green's function on a line. Here, we propose a two-step algorithm which, with two simulations, provides the full kernel on the domain. Moreover, our method is more accurate, as the singularity of the solution due to the Dirac source is described exactly. In addition, it is coupled with the exact Dirichlet-to-Neumann boundary condition, providing optimal accuracy in approximating the outgoing Green's kernel, which we demonstrate in our experiments. In addition, we show that high-frequency approximations of the nonlocal radiation boundary conditions can represent accurately the helioseismic products.

BackgroundIntegrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear.ObjectivesTo assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI.Patients and methodsPatients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat’AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART.ResultsFrom 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes.ConclusionsINSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.

International audience; In this work, we present an ultra-high Q cavity at Terahertz (THz) frequencies. The designed cavity is built on a low loss suspended silicon (Si) waveguide. The substrate removal under the waveguide and the use of optimized deep reactive ion etching processing is the main reason for observing very low losses of this design α< 0.09 dB/mm. This very low loss behavior of this designed platform is also demonstrated by the measurement of a 1D photonic wire crystal cavity with Q>18000. Different cavity layouts are adjusted in order to maximize the transmittance while maintaining high Q. A design with reduced number of etched crystal holes achieve a Q>1500 and high transmittance T>70%. These structures are presented at sub-mm waves (around 600GHz) for the design of a gas sensor in this frequency region, but the principles can be scaled and redesigned for other frequencies in the THz band.

Legionella pneumophila (Lp) is a water borne bacterium causing Legionnaires’ Disease (LD) in humans. Rapid detection of Lp in water system is essential to reduce the risk of LD outbreaks. The methods currently available require expert skills and are time intensive, thus delaying intervention. In situ detection of Lp by biosensor would allow rapid implementation of control strategies. To this end, a biorecognition element is required. Aptamers are considered promising biorecognition molecules for biosensing. Aptamers are short oligonucleotide sequence folding into a specific structure and are able to bind to specific molecules. Currently, no aptamer and thus no aptamer-based technology exists for the detection of Lp. In this study, Systemic Evolution of Ligands through EXponential enrichment (SELEX) was used to identify aptamers binding specifically to Lp. Ten rounds of positive selection and two rounds of counter-selection against two Pseudomonas species were performed. Two aptamers binding strongly to Lp were identified with KD of 116 and 135 nM. Binding specificity of these two aptamers to Lp was confirmed by flow cytometry and fluorescence microscopy. Therefore, these two aptamers are promising biorecognition molecules for the detection of Lp in water systems.

Coccolithophores are phytoplanktonic algae which produce an exoskeleton made of single platelets of calcite named coccoliths. They are widespread in all oceans and directly impact the short- and long-term C cycle. The study of coccolith size, morphology and elemental composition reveals important information regarding the ability of the cell to calcify and on the factors that influence this process. In this regard, very little is known about coccolith composition and its changes under altered environmental conditions. Here, we present high resolution (50 × 50 nm) elemental spatial distribution in pristine coccoliths of Coccolithus pelagicus and Gephyrocapsa oceanica reconstructed via X-ray fluorescence analyses at synchrotron. The studied specimens are from control culture and metal-enriched (V, Ni, Zn and Pb) experiments. The analysed specimens produced under stress conditions, display an irregular shape and are thinner, especially in the external rim, with ca. 1/3 lower Ca concentrations compared to specimens from the control. The same specimens also have higher Sr/Ca ratio with highest values in the coccolith external rim, suggesting that difficulty in calcification is additionally reflected in increased Sr/Ca ratios. Selenium is found in the coccolith as possible substitute of carbonate in the calcite. V and Pb apparently did not interact with the coccoliths while Zn and Ni were deposited on the coccolith surface.

In large-building water systems, Legionella pneumophila is exposed to common environmental stressors such as copper. The aim of this study was to evaluate the susceptibility to copper of L. pneumophila isolates recovered from various sites: two clinical and seven environmental from hot water systems biofilm & water, and from cooling tower water. After one-week acclimation in simulated drinking water, strains were exposed to various copper concentrations (0.8 to 5 mg/L) for over 672 hours. Complete loss of culturability was observed for three isolates, following copper exposure to 5 mg/L for 672h. Two ST1427-like isolates were highly sensitive to copper, while the other two, isolated from biofilm samples, were resistant. The expression of the copper resistance gene copA evaluated by RT-qPCR was significantly higher for the biofilm isolates. All four ST1427-like isolates were recovered from the same water system during an outbreak. Whole genome sequencing results confirmed that the four isolates are very close phylogenetically, differing by only 29 single nucleotide polymorphisms, suggesting in situ adaptation to microenvironmental conditions, possibly due to epigenetic regulation. These results indicate that the immediate environment within a building water distribution system influences the tolerance of L. pneumophila to copper. Increased contact of L. pneumophila biofilm strains with copper piping or copper alloys in the heat exchanger might lead to local adaptation. The phenotypic differences observed between water and biofilm isolates from the hot water system of a healthcare facility warrants further investigation to assess the relevance of evaluating disinfection performances based on water sampling alone.ImportanceLegionella pneumophila is a pathogen indigenous to natural and large building water systems in the bulk and the biofilm phases. The immediate environment within a system can impact the tolerance of L. pneumophila to environmental stressors, including copper. In healthcare facilities, copper levels in water can vary, depending on water quality, plumbing materials and age. This study evaluated the impact of the isolation site (water vs biofilm, hot water system vs cooling tower) within building water systems. Closely related strains isolated from a healthcare facility hot water system exhibited variable tolerance to copper stress shown by differential expression of copA, with biofilm isolates displaying highest expression and tolerance. Relying on the detection of L. pneumophila in water samples following exposure to environmental stressor such as copper may underestimate the prevalence of L. pneumophila, leading to inappropriate risk management strategies and increasing the risk of exposure for vulnerable patients.

International audience; The increasing application of Quantum Dots (QDs) is cause of concern for the potential negative effects for the ecosystem, especially in soils that may act as a sink. In this study, soil leaching experiments were performed in quartz sand packed columns to investigate the behavior of core-shell CdSe/ZnS QDs coated with either small ligands (TGA-QDs) or more complex polymers (POAMA-QDs). Fluorescence emission was compared to mass spectrometric measurements to assess the nanoparticles (NPs) state in both the leachate (transported species) and porous media (deposited amounts). Although both QDs were strongly retained in the column, large differences were observed depending on their capping ligand stability. Specifically, for TGA-QDs elution was negligible and the retained fraction accumulated in the top-columns. Furthermore, 74% of the NPs were degraded and 38% of the Se was found in the leachate in non-NPs state. Conversely, POAMA-QDs were recovered to a larger extent (78.1%), and displayed a higher transport along the soil profile. Further experiments with altered NPs showed that homo-aggregation of the QDs prior injection determined a reduced mobility but no significant changes in their stability. Eventually, ageing of the NPs in the column (15 days) caused the disruption of up to 92% of the original QDs and the immobilization of NPs and metals. These results indicate that QDs will accumulate in top-soils, where transformations phenomena will determine the overall transport, persistency and degradation of these chemicals. Once accumulated, they may act as a source for potentially toxic Cd and Se metal species displaying enhanced mobility.

BackgroundAcute respiratory failure (ARF) is a life-threatening complication in onco-hematology patients. Optimal ventilation strategy in immunocompromised patients has been highly controversial over the last decade. Data are lacking on patients presenting with ARF associating isolated cardiac dysfunction or in combination with another etiology. The aim of this study was to assess prognostic impact of initial ventilation strategy in onco-hematology patients presenting ARF with associated cardiac dysfunction.MethodsWe conducted an observational retrospective study in Institut Paoli-Calmettes, a cancer-referral center, assessing all critically ill cancer patients admitted to the ICU for a ARF with cardiac dysfunction.ResultsBetween 2010-2017, 127 patients were admitted. ICU and hospital mortality were 29% and 57%. Initial ventilation strategy was invasive mechanical ventilation (MV) in 21%. Others ventilation strategies were noninvasive ventilation (NIV) in 50%, associated with oxygen in 21% and high flow nasal oxygen (HFNO) in 29%, HFNO alone in 6% and standard oxygen in 23%. During ICU stay, 48% of patients required intubation. Multivariate analysis identified 3 independent factors associated with ICU mortality: SAPSII at admission (OR = 1.07/point, 95%CI = 1.03-1.11, pConclusionIn onco-hematology patients admitted for ARF with associated cardiac dysfunction, severity at ICU admission, invasive fungal infections and initial ventilation strategy were independently associated with ICU mortality. NIV was a protective factor on ICU mortality.

Legionella are waterborne bacteria and the causative agents behind a severe respiratory disease known as Legionnaires Disease (LD). Standard ISO-certified methods to detect Legionella (plate count and qPCR) are time-consuming and tedious necessitating the development of novel detection strategies. This study introduces an SPRi-based titration assay that uses L. pneumophila (Lp) aptamers. Multiple parameters including buffer conditions, aptamer concentrations, complementary aptamer probe (cApt) concentrations and incubation times were investigated and evaluated for optimal signal response. For maximum hybridization efficiency on the sensor surface, high salt buffer (SSC) as well 500 nM of immobilized cApt resulted in a maximum signal response. Additionally, it was observed that of the three buffers (PBS, Fraquil, SSC) tested in this assay only SSC facilitated incremental binding of aptamers to Lp such that varying concentrations of Lp could be determined. We were able to detect varying concentrations of Lp down to a limit of 104 cells/ml without any sample processing or signal amplification steps, highlighting the potential of this system for SPRi-based Lp detection. The assay is also specific to Lp and shows negligible detection of Pseudomonas, a common inhabitant of water systems.

Heterogeneous catalysts have been widely used for chemical transformations and offer easy product separation in addition to their high activity. Iron is an earth-abundant metal, but it has not been studied thoroughly as heterogeneous catalysts for organic reactions. In this work, supported iron catalysts were synthesized via loading FeCl3 onto a mesoporous silica SBA-15. These catalysts were highly active for Michael addition reactions, a synthetic pathway for forming C C bonds that is typically achieved by homogeneous catalysts. Our studies show that for the supported iron catalysts, larger pore sizes of the silica resulting from the loading of iron and the oxidation state of iron being Fe(III) are essential for the high reaction rates. Notably, the catalysts show stability against leaching, regardless the presence or absence of a dendrimer as an additional stabilizing agent. The catalysts could be used for at least three runs without the loss of activity. The successful Michael addition reactions of indole or 2-methylindole and different α,β-unsaturated ketones corroborate the synthetic scope of the catalysts. These results show promises of using supported iron catalysts as inexpensive and effective alternatives for the formation of C C bonds.

The identity of the active sites of hydrophobic Lewis acid zeolites was elucidated by solid-state 31P nuclear magnetic resonance (NMR) spectroscopy following adsorption of trimethylphosphine oxide (TMPO) probe molecules. The adsorption of TMPO on these materials resulted in distinct 31P NMR resonances between δiso = 59.9 and 54.9 ppm that correspond to unique chemical environments of the Lewis acidic heteroatoms in the Beta zeolite framework. The 31P NMR resonances were assigned to sites in Sn-Beta zeolites by correlating the variation of 31P NMR spectra during TMPO titration experiments with the corresponding changes in the 119Sn NMR spectra. This method allowed us to establish quantitative relationships between the assignments for each site and the catalytic activity for the glucose isomerization and aldol condensation reactions. The rate of glucose isomerization directly correlated with the combined integrated intensities of 31P MAS NMR resonances at δiso = 55.8 and 54.9 ppm, which amounted to 12–33% o...

Electrodialysis with bipolar membrane (EDBM) is promising to recover phospholipids (PLs) from sweet whey and whey protein concentrate (WPC), as it promotes lipoprotein complex formation following a decrease in pH and ionic strength. The aim of this work was to study the impact of dilution factor (without dilution, with a 2X, 4X and 6X dilution) after EDBM on the process performances. For both products, a 4X dilution, which corresponds to a decrease in ionic strength of 81.4 ± 1.5 % for sweet whey and 79.4 ± 0.4 % for WPC, seemed sufficient to maximize lipoprotein complex formation as a plateau was reached in the defatting rates. Furthermore, it was demonstrated that the process could be used to recover PLs. Higher PL contents were found in the precipitates recovered from sweet whey combined with a dilution: highest contents in total PLs for WPC (7.45 ± 0.49 and 8.00 ± 0.49 g/100g with a 4X-6X dilution) were not different from the lowest content for sweet whey (7.50 ± 1.18 g/100 g without dilution). For both products, the main PLs recovered were phosphatidylethanolamine and phosphatidylserine, which respectively represented between 42.0 ± 1.7 and 51.6 ± 2.3 % and 30.1 ± 2.2 to 38.7 ± 0.8 % of total PLs. Furthermore, considering their high ecoefficiency scores, sweet whey combined with a 2X or 4X dilution are the most promising conditions.