Vers la classification darwinienne d'un processeur fossile

This paper has been awarded "Editor's Choice" of the RAFT 2008 proceedings.National audienceÉvolutionnistes et créationnistes s'affrontent sur tous les plans afin d'imposer à l'ensemble de la communauté leurs idées quant à la disparition d'anciennes espèces. Le domaine de la recherche en informatique et plus particulièrement de la paléoprocessologie est d'autant plus sensible à ce débat que l'extension des laboratoires sur les campus révèle la présence d'un grand nombre de fossiles encore non identifiés. Cet article, véritable étude de cas, présente une approche expérimentale protocolaire visant à la classification d'un processum sorórem fossilis non identifié

Thyroid-stimulating hormone pulses finely tune thyroid hormone release and TSH receptor transduction

Detection of circulating thyroid-stimulating hormone (TSH) is a first-line test of thyroid dysfunction, a major health problem (affecting about 5% of the population) that, if untreated, can lead to a significant deterioration of quality of life and adverse effects on multiple organ systems. Human TSH levels display both pulsatile and (non-pulsatile) basal TSH secretion patterns; however, the importance of these in regulating thyroid function and their decoding by the thyroid is unknown. Here, we developed a novel ultra-sensitive ELISA that allows precise detection of TSH secretion patterns with minute resolution in mouse models of health and disease. We characterised the patterns of ultradian TSH pulses in healthy, freely-behaving mice over the day-night cycle. Challenge of the thyroid axis with primary hypothyroidism due to iodine deficiency, a major cause of thyroid dysfunction worldwide, results in alterations of TSH pulsatility. Induction in mouse models of sequential TSH pulses that mimic ultradian TSH profiles in periods of minutes were more efficient than sustained rises in basal TSH levels at increasing both thyroid follicle cAMP levels, as monitored with a genetically-encoded cAMP sensor, and circulating thyroid hormone (TH). Hence this mouse TSH assay provides a powerful tool to decipher how ultradian TSH pulses encode thyroid outcomes, and to uncover hidden parameters in the TSH-TH set-point in health and disease.</p

Detecting and Characterizing Mg II absorption in DESI Survey Validation Quasar Spectra

In this paper we will present findings on the detection of Magnesium II (MgII, lambda = 2796 {\AA}, 2803 {\AA}) absorption systems observed in data from the Early Data Release (EDR) of the Dark Energy Spectroscopic Instrument (DESI). DESI is projected to obtain spectroscopy of approximately 3 million quasars (QSOs), of which over 99% are anticipated to be found at redshifts greater than z < 0.3, such that DESI would be able to observe an associated or intervening Mg II absorber illuminated by the background QSO. We have developed an autonomous supplementary spectral pipeline that detects such systems through an initial line-fitting process and then confirms line properties using a Markov Chain Monte Carlo (MCMC) sampler. Based upon both a visual inspection and the reanalysis of coadded observations, we estimate this sample of absorption systems to have a completeness of 82.56% and purity of 99.08%. As the spectra in which Mg II systems are detected are the result of coadding multiple observations, we can determine the sensitivity, and therefore completeness, of the sample by searching for known Mg II systems in coadded data with fewer observations (and therefore lower signal-to-noise). From a parent catalog containing 83,207 quasars, we detect a total of 23,921 Mg II absorption systems following a series of quality cuts. Extrapolating from this occurrence rate of 28.75% implies a catalog at the completion of the five-year DESI survey that contains over eight hundred thousand Mg II absorbers. The cataloging of these systems will enable significant further research as they carry information regarding circumgalactic medium (CGM) environments, the distribution of intervening galaxies, and the growth of metallicity across the redshift range 0.3 < z < 2.5.Comment: 12 pages, 7 figure

The DESI survey validation : results from visual inspection of bright galaxies, luminous red galaxies, and emission line galaxies

Funding: TWL was supported by the Ministry of Science and Technology (MOST 111-2112-M-002-015-MY3), the Ministry of Education, Taiwan (MOE Yushan Young Scholar grant NTU-110VV007), National Taiwan University research grants (NTU CC-111L894806, NTU- 111L7318), and NSF grant AST-1911140. DMA acknowledges the Science Technology and Facilities Council (STFC) for support through grant code ST/T000244/1. This research is supported by the Director, Office of Science, Office of High Energy Physics of the U.S. Department of Energy under Contract No. DE–AC02–05CH11231, and by the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility under the same contract; additional support for DESI is provided by the U.S. National Science Foundation, Division of Astronomical Sciences under Contract No. AST-0950945 to the NSF’s National Optical-Infrared Astronomy Research Laboratory; the Science and Technologies Facilities Council of the United Kingdom; the Gordon and Betty Moore Foundation; the Heising-Simons Foundation; the French Alternative Energies and Atomic Energy Commission (CEA); the National Council of Science and Technology of Mexico (CONACYT); the Ministry of Science and Innovation of Spain (MICINN), and by the DESI Member Institutions: https://www.desi.lbl.gov/ collaborating-institutions.The Dark Energy Spectroscopic Instrument (DESI) Survey has obtained a set of spectroscopic measurements of galaxies for validating the final survey design and target selections. To assist these tasks, we visually inspect (VI) DESI spectra of approximately 2,500 bright galaxies, 3,500 luminous red galaxies, and 10,000 emission line galaxies, to obtain robust redshift identifications. We then utilize the VI redshift information to characterize the performance of the DESI operation. Based on the VI catalogs, our results show that the final survey design yields samples of bright galaxies, luminous red galaxies, and emission line galaxies with purity greater than 99%. Moreover, we demonstrate that the precision of the redshift measurements is approximately 10 km/s for bright galaxies and emission line galaxies and approximately 40 km/s for luminous red galaxies. The average redshift accuracy is within 10 km/s for the three types of galaxies. The VI process also helps to improve the quality of the DESI data by identifying spurious spectral features introduced by the pipeline. Finally, we show examples of unexpected real astronomical objects, such as Lyman α emitters and strong lensing candidates, identified by VI. These results demonstrate the importance and utility of visually inspecting data from incoming and upcoming surveys, especially during their early operation phases.Publisher PDFPeer reviewe

ANK2 loss-of-function variants are associated with epilepsy, and lead to impaired axon initial segment plasticity and hyperactive network activity in hiPSC-derived neuronal networks

PURPOSE: To characterize a novel neurodevelopmental syndrome due to loss-of-function (LoF) variants in Ankyrin 2 (ANK2), and to explore the effects on neuronal network dynamics and homeostatic plasticity in human-induced pluripotent stem cell-derived neurons. METHODS: We collected clinical and molecular data of 12 individuals with heterozygous de novo LoF variants in ANK2. We generated a heterozygous LoF allele of ANK2 using CRISPR/Cas9 in human-induced pluripotent stem cells (hiPSCs). HiPSCs were differentiated into excitatory neurons, and we measured their spontaneous electrophysiological responses using micro-electrode arrays (MEAs). We also characterized their somatodendritic morphology and axon initial segment (AIS) structure and plasticity. RESULTS: We found a broad neurodevelopmental disorder (NDD), comprising intellectual disability, autism spectrum disorders and early onset epilepsy. Using MEAs, we found that hiPSC-derived neurons with heterozygous LoF of ANK2 show a hyperactive and desynchronized neuronal network. ANK2-deficient neurons also showed increased somatodendritic structures and altered AIS structure of which its plasticity is impaired upon activity-dependent modulation. CONCLUSIONS: Phenotypic characterization of patients with de novo ANK2 LoF variants defines a novel NDD with early onset epilepsy. Our functional in vitro data of ANK2-deficient human neurons show a specific neuronal phenotype in which reduced ANKB expression leads to hyperactive and desynchronized neuronal network activity, increased somatodendritic complexity and AIS structure and impaired activity-dependent plasticity of the AIS

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Vers la classification darwinienne d'un processeur fossile

This paper has been awarded "Editor's Choice" of the RAFT 2008 proceedings.National audienceÉvolutionnistes et créationnistes s'affrontent sur tous les plans afin d'imposer à l'ensemble de la communauté leurs idées quant à la disparition d'anciennes espèces. Le domaine de la recherche en informatique et plus particulièrement de la paléoprocessologie est d'autant plus sensible à ce débat que l'extension des laboratoires sur les campus révèle la présence d'un grand nombre de fossiles encore non identifiés. Cet article, véritable étude de cas, présente une approche expérimentale protocolaire visant à la classification d'un processum sorórem fossilis non identifié

Une approche décentralisée à base de chroniques pour la surveillance et le diagnostic de services web

Ce travail de thèse étend au cadre distribué et plus précisément à la surveillance de services web l'approche de type reconnaissance de chroniques, adaptée au diagnostic de systèmes à évènements discrets. Lorsqu'une requête est envoyée à un service web, celui-ci coopère avec d'autres services pour fournir une réponse adaptée à la demande. Des fautes peuvent se propager d'un service à l'autre et, afin d'y réagir convenablement, leur diagnostic est un problème crucial. Le formalisme des chroniques a été proposé il y a quelques années dans le but de surveiller des systèmes dynamiques en temps réel. Une chronique, caractérisée par un ensemble d'évènements temporellement contraints, décrit les situations à surveiller. Il existe des algorithmes efficaces de reconnaissance de chroniques à la volée, mais toujours dans un cadre centralisé. On sait maintenant que les approches distribuées sont plus adaptées à la surveillance de systèmes réels. La contribution de cette thèse est d'étendre l'approche à base de chroniques au contexte distribué. Nous proposons ainsi une extension du formalisme des chroniques ainsi que deux architectures décentralisées dont le but commun est, en fusionnant des diagnostics locaux calculés par des reconnaisseurs de chroniques, d'obtenir un diagnostic global permettant d'élaborer un plan de réparation centralisé. Ces deux architectures se différencient par l'utilisation ou non d'un modèle global des interactions entre services web. Ce travail a été motivé par une application visant à surveiller le comportement de composants logiciels, au sein du projet européen WS-Diamond.This work extends the chronicle recognition approach, commonly employed for diagnosing discrete event systems, to a distributed context and more precisely to the monitoring of web services. When a web service is sent a request, it collaborates with other services so as to provide its client with the expected answer. Faults may propagate from one service to another and, in order to react properly, diagnosing them is a key issue. The formalism of chronicles has been proposed a few years ago in order to monitor dynamic systems in real time. A chronicle, characterized by a set of temporally constrained events, describes the situations to monitor. Efficient algorithms allowing chronicle recognition on the fly exist, but in centralized cases only. It is now well-known that distributed approaches are well-suited to the monitoring of real systems. This PhD thesis aims at extending the chronicle-based approach to a distributed context. We propose an extension of the formalism of chronicles and two decentralized architectures whose common goal is, by merging local diagnoses computed by chronicle recognition systems, to obtain a global diagnosis allowing to elaborate a centralized repair plan. The main difference between those architectures consists in a global model of the interactions between services that is only used by one architecture. This work has been motivated by an application aiming at monitoring the behavior of software components, within the framework of the WS-Diamond european project.RENNES1-BU Sciences Philo (352382102) / SudocRENNES-INRIA Rennes Irisa (352382340) / SudocSudocFranceF