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With this contribution we show the readout electronics for kinetic inductance detectors (KIDs) that we are developing based on commercial IQ transceivers from National Instruments and using a Virtex 5 class FPGA. It will be the readout electronics of the COSmic Monopole Observer (COSMO) experiment, a ground based cryogenic Martin–Puplett Interferometer searching for the cosmic microwave background spectral distortions. The readout electronics require a sampling rate in the range of tens of kHz, which is both due to a fast rotating mirror modulating the signal and the time constant of the COSMO KIDs. In this contribution we show the capabilities of our readout electronics using Niobium KIDs developed by Paris Observatory for our 5 K cryogenic system. In particular, we demonstrate the capability to detect 23 resonators from frequency sweeps and to readout the state of each resonator with a sampling rate of about 8 kHz. The readout is based on a finite-state machine where the first two states look for the resonances and generate the comb of tones, while the third one performs the acquisition of phase and amplitude of each detector in free running. Our electronics are based on commercial modules, which brings two key advantages: they can be acquired easily and it is relative simple to write and modify the firmware within the LabView environment in order to meet the needs of the experiment.

We are developing superconducting Microwave Kinetic Inductance Detectors to operate at near infrared and optical wavelengths for astronomy. In order to efficiently meet with the requirements of astronomical applications, we propose to replace the interdigitated capacitor by a metal–insulator–metal capacitor which has the advantage of presenting a larger capacitance value within a much smaller space. The pixel will occupy a space of typically 100 × 85 µm which is nine times less than a typical pixel size using the interdigitated capacitor operating at the same frequency, below 2 GHz.

We are developing superconducting Microwave Kinetic Inductance Detectors to operate at near infrared and optical wavelengths for astronomy. In order to efficiently meet with the requirements of astronomical applications, we propose to replace the interdigitated capacitor by a metal, insulator, metal capacitor which has the advantage of presenting a larger capacitance value within a much smaller space. The pixel will occupy a space of typically 100 micrometers by 85 micrometers which is nine times less than a typical pixel size using the interdigitated capacitor operating at the same frequency, below 2 GHz.

We study experimentally and numerically the zero-voltage supercurrent vs. magnetic field of non-uniform arrays of Josephson junctions parallel-connected by a superconducting stripline. The measured curves are complex, unique and in excellent agreement with numerical simulations using a specially developed model. Using this, we can optimize the arrays to have any desired interference pattern. Such new devices could find applications in magnetometry, quasiparticle mixers and detectors, flux-flow oscillators and superconducting electronics.

This work is focused on the microstructure study of nickel aluminide (Ni-5wt.%Al) deposited on an A37 steel substrate using Rietveld refinement of x-ray diffraction data. These coatings are elaborated by atmospheric plasma spray, which consists of introducing the initial feedstock material, in the form of powder, into a flame of 20,000°C temperature, melting it and spraying it on a surface to coat. The deposit was realized on two types of substrates: the first was on a non-heated substrate, and the second coating was deposited on a heated substrate at 150°C. X-ray diffraction analyses are conducted on the coating to investigate its microstructure and phases, with the Rietveld refinement technique employed to quantify the various phases present. The results showed that the nickel aluminide coatings present the formation of new phases such as Ni 3 Al and NiO. The surface roughness and micro-hardness values of the coatings have also been evaluated, and the mean hardness of the coating was found to be about 476 H V and 493 Hv for coatings deposited on non-heated and heated substrates, respectively.

Background Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH) 2 D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH) 2 D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH) 2 D levels. Methods The FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double-blind trial. A total of 60 patients (10–60 years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/day), increased 1,25(OH) 2 D levels (> 150 pmol/L), and 25-OH-D levels >20 nmol/L will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-h calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-h calciuria in patients who still display at W16 a 24-h hypercalciuria. Discussion The current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH) 2 D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the “off-label” use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH) 2 D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. Trial registration ClinicalTrials.gov NCT04495608 . Registered on July 23, 2020.

Fertility quantitative trait loci (QTL) are of high interest in dairy cattle since insemination failure has dramatically increased in some breeds such as Holstein. High-throughput SNP analysis and SNP microarrays give the opportunity to genotype many animals for hundreds SNPs per chromosome. In this study, due to these techniques a dense SNP marker map was used to fine map a QTL underlying nonreturn rate measured 90 days after artificial insemination previously detected with a low-density microsatellite marker map. A granddaughter design with 17 Holstein half-sib families (926 offspring) was genotyped for a set of 437 SNPs mapping to BTA3. Linkage analysis was performed by both regression and variance components analysis. An additional analysis combining both linkage analysis and linkage-disequilibrium information was applied. This method first estimated identity-by-descent probabilities among base haplotypes. These probabilities were then used to group the base haplotypes in different clusters. A QTL explaining 14% of the genetic variance was found with high significance (P < 0.001) at position 19 cM with the linkage analysis and four sires were estimated to be heterozygous (P < 0.05). Addition of linkage-disequilibrium information refined the QTL position to a set of narrow peaks. The use of the haplotypes of heterozygous sires offered the possibility to give confidence in some peaks while others could be discarded. Two peaks with high likelihood-ratio test values in the region of which heterozygous sires shared a common haplotype appeared particularly interesting. Despite the fact that the analysis did not fine map the QTL in a unique narrow region, the method proved to be able to handle efficiently and automatically a large amount of information and to refine the QTL position to a small set of narrow intervals. In addition, the QTL identified was confirmed to have a large effect (explaining 13.8% of the genetic variance) on dairy cow fertility as estimated by nonreturn rate at 90 days.

BackgroundLymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7.ResultsPeripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients.ConclusionsSevere COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far.Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.

WWOX (WW domain-containing oxidoreductase) is the gene mapping at FRA16D HSA16q23.1, the second most active common fragile site in the human genome. In this study we characterized at a detailed molecular level WWOX in the bovine genome. First, we sequenced cDNA from various tissues and obtained evidence in support of a 9-exon structure for the gene, similar to the human gene. Then, we recovered BACs using exon tags and annotated the gene to a >1-Mb genomic region of BTA18 using the Btau 4.0 genome assembly as a reference, thus resolving an issue related to exon 9, which is not included in the genomic annotation of the gene in the Entrez database. Finally, BACs spanning WWOX were used as FISH probes to obtain comparative mapping of the gene in Bos taurus, Bubalus bubalis, Ovis aries and Capra hircus to BTA18q12.1, BBU18q13, OAR14q12.1 and CHI18q12.1, respectively. Our data show that the chromosomal location of WWOX is conserved between man and 4 major domesticated species. Moreover, the annotation of the bovine gene also suggests a highly conserved genomic arrangement, including number and size of introns.

DNA fingerprints and end sequences from bacterial artificial chromosomes (BACs) from two new libraries were generated to improve the first generation integrated physical and genetic map of the rainbow trout (Oncorhynchus mykiss) genome. The current version of the physical map is composed of 167,989 clones of which 158,670 are assembled into contigs and 9,319 are singletons. The number of contigs was reduced from 4,173 to 3,220. End sequencing of clones from the new libraries generated a total of 11,958 high quality sequence reads. The end sequences were used to develop 238 new microsatellites of which 42 were added to the genetic map. Conserved synteny between the rainbow trout genome and model fish genomes was analyzed using 188,443 BAC end sequence (BES) reads. The fractions of BES reads with significant BLASTN hits against the zebrafish, medaka, and stickleback genomes were 8.8%, 9.7%, and 10.5%, respectively, while the fractions of significant BLASTX hits against the zebrafish, medaka, and stickleback protein databases were 6.2%, 5.8%, and 5.5%, respectively. The overall number of unique regions of conserved synteny identified through grouping of the rainbow trout BES into fingerprinting contigs was 2,259, 2,229, and 2,203 for stickleback, medaka, and zebrafish, respectively. These numbers are approximately three to five times greater than those we have previously identified using BAC paired ends. Clustering of the conserved synteny analysis results by linkage groups as derived from the integrated physical and genetic map revealed that despite the low sequence homology, large blocks of macrosynteny are conserved between chromosome arms of rainbow trout and the model fish species.