Contrôle actif par Simulation aux Grandes Echelles d'un écoulement de canal turbulent

Dans cette étude, nous analysons en terme de réduction de traînée moyenne et d'efficacité énergétique l'influence de la position du plan de détection et du nombre de Reynolds sur une stratégie de contrôle par opposition. Il s'avère que pour un nombre de Reynolds fixé, la position du plan de détection associée au maximum de réduction de traînée semble correspondre aux régions de production de la turbulence. Nos résultats confirment que la réduction de traînée diminue avec l'augmentation du nombre de Reynolds et que l'efficacité énergétique est maximale pour une position du plan de détection différente de celle correspondant au maximum de réduction de traînée

Contrôle optimal par Simulation aux Grandes Echelles d’un écoulement de canal turbulent

Une stratégie de contrôle optimal est mise en œuvre pour réduire par soufflage/aspiration aux parois la traînée d’un écoulement de canal plan tridimensionnel. Ici, contrairement à l’étude de Bewley et al. (2001),  une Simulation aux Grandes Echelles est utilisée comme modèle réduit des équations de Navier-Stokes. Pour Ret=100, le contrôle parvient à relaminariser complètement l’écoulement alors que pour Ret=180, une réduction de traînée de 55% est obtenue mais sans relaminarisation

Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3

Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigate the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice results in restructuring of the chromatin architecture. This leads to ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern induced by AER-specific enhancers of Fgf8. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression in the developing limb. Our results reveal insights into the molecular mechanism underlying SHFM3 and provide conceptual framework for how genomic rearrangements can cause gene misexpression and disease.This study was supported by grants from the Deutsche Forschungsgemeinschaft (MU 880/16-1, MU 880/20-1) to S.M. We thank the transgenic unit, sequencing core and animal facility of Max Planck Institute for Molecular Genetics for technical assistance, Ute Fischer for technical support and Norbert Brieske for help with whole mount in situ hybridizations and image processing

Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7‐related osteopetrosis

Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte-like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage-specific gene and surface marker expression proved mesodermal priming, the presence of monocyte-like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)-derived osteoclasts hiPSC-derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC-osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002-A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl-/H+-exchanger ClC-7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC-7 displayed residual expression and retained lysosomal co-localization with OSTM1, the gene coding for the osteopetrosis-associated transmembrane protein 1, but only ClC-7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC-derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss-of-function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC-osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast-related diseases. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Entwurf und Implementierung von sicheren Smart-Contracts für mobile Objektverfolgungssysteme

In recent years, cryptocurrencies implemented on top of Blockchains became very popular, with Bitcoin as the most prominent example. However, novel Blockchain-based platforms such as Ethereum also support distributed applications beyond cryptocurrencies through so-called smart contracts. Technically, smart contracts are programs, whose code and execution state is stored in the Blockchain, inherently featuring the ability to transfer (electronic) money during their execution. In this Bachelor thesis, we investigate how smart contracts can be used to implement a distributed crowdsensing application for tracking mobile objects by a crowd of privately owned mobile devices. Such a system could be used, for instance, to nd lost or stolen objects, such as keys, vehicles (cars, bicycles, . . . ), or pets tagged with short-range radio transmitters implemented using readily available Bluetooth or RFID technology. These objects can then be detected by smartphones of private users in the vicinity of the object, effectively implementing a huge sensor network covering many parts of the world without any upfront investments by a central entity. Although highly attractive, implementing a crowdsensing application on top of a Blockchain platform such as Ethereum comes with several challenges. First of all, users need incentives to participate in searching for mobile objects. A natural incentive is a monetary reward that participants automatically receive through the smart contract when reporting sightings (timestamped positions) of wanted objects. However, this directly brings up the problem of malicious participants (attackers) who try to get the reward without actually executing the work of searching for the object by simply reporting fake positions. Therefore, one major goal of this Bachelor thesis is to counter such attacks by proposing effective counter-measures, and implementing and evaluating them for the Ethereum platform. In detail, we propose a basic reputation-based approach for detecting fake positions which judges each sighting made by a mobile devices according to the reputation of that device, implemented by a smart contract. Furthermore, advanced attacks are identified compromising the basic reputation-based approach and effective counter-measures to these advanced attacks are proposed. Identified advanced attacks include reputation farming, where the attacker tries to aggregate reputation first before launching the attack, and the so-called copycat attack, where the attacker simply copies already submitted valid sightings form honest participants, making his fake positions indistinguishable from valid positions. Our evaluations analyses the monetary cost of executing smart contracts with and without our security mechanisms. The results show that the overhead included by our reputation-based approach is at maximum 45% of the cost of a smart contract without implemented security mechanisms.In den letzten Jahren wurden Kryptowährungen, die auf Blockchains basieren, sehr populär, mit Bitcoin als prominentestem Beispiel. Neuartige Blockchain-basierte Plattformen, wie Ethereum, unterstützen jedoch auch verteilte Anwendungen jenseits von Kryptowährungen durch so genannte Smart Contracts. Technisch gesehen handelt es sich bei Smart Contracts um Programme, deren Code und Ausführungszustand in der Blockchain gespeichert wird und die inhärent die Fähigkeit besitzen, während ihrer Ausführung (elektronisches) Geld zu transferieren. In dieser Bachelorarbeit wird untersucht, wie Smart Contracts dazu verwendet werden können, eine verteilte Crowdsensing-Anwendung zur Verfolgung mobiler Objekte durch eine Menge privater mobiler Geräte zu implementieren. Ein solches System könnte z.B. dazu verwendet werden, verlorene oder gestohlene Gegenstände wie Schlüssel, Fahrzeuge (Autos, Fahrräder, ...) oder Haustiere zu finden, die mithilfe von leicht verfügbaren Bluetooth- oder RFID-Technologie implementierten Funksendern ausgestattet sind. Diese Gegenstände können dann von Smartphones privater Nutzer in der Nähe des Objekts erkannt werden, wodurch ein riesiges Sensornetzwerk entsteht, das viele Teile der Welt abdeckt und ohne Vorabinvestitionen durch eine zentrale Entität aufgesetzt werden kann. Obwohl die Implementierung einer Crowdsensing-Anwendung auf einer Blockchain-Plattform wie Ethereum attraktiv ist, bringt sie auch einige Herausforderungen mit sich. Zunächst benötigen die Benutzer Anreize, sich an der Suche nach mobilen Objekten zu beteiligen. Ein natürlicher Anreiz ist eine monetäre Belohnung, die die Teilnehmer durch den Smart Contract automatisch erhalten, wenn sie Sichtungen (Positionen mit einem Zeitstempel) gesuchter Objekte melden. Dies wirft jedoch direkt das Problem böswilliger Teilnehmer (Angreifer) auf, die versuchen, die Belohnung zu erhalten, ohne den Aufwand der Suche nach dem Objekt tatsächlich nachzugehen, indem sie einfach falsche Positionen melden. Ein Ziel dieser Bachelorarbeit ist es daher, solchen Angriffen durch den Entwurf wirksamer Gegenmaßnahmen zu begegnen und diese für die Ethereum-Plattform zu implementieren und auszuwerten. Im Einzelnen schlagen wir einen grundlegenden, durch einen Smart Contract implementierten reputationsbasierten Ansatz für die Erkennung von gefälschten Positionen vor, der jede Sichtung durch ein mobiles Gerät nach der Reputation dieses Geräts beurteilt. Darüber hinaus werden fortgeschrittene Angriffe identifiziert, die den grundlegenden reputationsbasierten Ansatz gefährden, sowie wirksame Gegenmaßnahmen gegen diese fortgeschrittenen Angriffe vorgeschlagen. Zu den identifizierten fortgeschrittenen Angriffen gehören so genannte Reputation-Farming-Angriffe, bei denen der Angreifer zuerst versucht, Reputation zu aggregieren, bevor er den Angriff startet. Des Weiteren wird der so genannte Copy-Cat-Angriff identifiziert und behandelt, bei dem der Angreifer bereits eingereichte gültige Sichtungen von ehrlichen Teilnehmern kopiert, so dass seine gefälschten Positionen nicht von gültigen Positionen unterschieden werden können. Unsere Bewertung analysiert die monetären Kosten der Ausführung von Smart Contracts mit und ohne unsere Sicherheitsmechanismen. Die Ergebnisse zeigen, dass die von unserem reputationsbasierten Ansatz verursachten Mehrkosten maximal 45% betragen

The Role of Psychological Empowerment in Reducing the Level of Occupational Burnout among Teachers

International audiencePsychological empowerment is considered one of the modern concepts in the field of human behavior within organizations. Employee empowerment strategies are the basis of modern management policies in contemporary organizations. These organizations depend on the concepts of total quality, work development, employees' competence, and independence. Adopting the approach of psychological empowerment of the human resource and making him feel that he has a degree of independence and freedom in administrative practice at the level of all parts of the horizontal flexible organizational structure affects the degree of his performance as well as his belonging to the organization and achieving a degree of harmony and compatibility within the work environment. As a result, psychological empowerment is regarded as an effective tool in reducing psychological burnout in the educational, professional environment. The study aimed to identify the role of psychological empowerment in reducing the level of occupational burnout among teachers (a field study on a sample of primary school teachers in the province of Boumerdes). The descriptive-analytic method was used in order to achieve the objectives of the study. Two questionnaires have been approved after reviewing the theoretical literature on the subject of the study. The first relates to psychological empowerment, consisting of five dimensions, while the second relates to psychological burnout, which in turn also consists of three dimensions. This is after confirming their psychometric characteristics honestly and consistently. The research tool was applied to a sample of 98 teachers. And after statistically analyzing the data using the SSPS program version N. (22)

Contrôle optimal par simulation aux grandes échelles d'un écoulement turbulent

Deux stratégies de contrôle ont été successivement mises en œuvre pour réduire la traînée et l énergie cinétique turbulente d un canal plan en régime turbulent (Re[tau]=180) par soufflage/aspiration aux parois. L objectif principal était de prouver qu une simulation aux grandes échelles (LES) pouvait être utilisée de manière pertinente comme modèle réduit des équations de Navier-Stokes et ainsi diminuer fortement les coûts numériques. Une approche heuristique dite de contrôle par opposition a d abord été employée. Les résultats montrent que l'efficacité énergétique est maximale pour une position du plan de détection différente de celle qui correspond au maximum de réduction de traînée. Par ailleurs, nos résultats confirment que la réduction de traînée diminue avec l'augmentation du nombre de Reynolds. Par la suite, une procédure de contrôle optimal a été utilisée en considérant différentes fonctionnelles objectif (traînée, énergie cinétique au temps terminal, énergie cinétique moyen). Pour Re[tau]=100, le contrôle est parvenu à relaminariser complètement l écoulement (réduction de traînée de l'ordre de 50 %) en prenant comme fonctionnelle coût l énergie cinétique au temps terminal. Pour cette même fonctionnelle coût, une réduction importante de traînée de l'ordre de 55 % est encore obtenue à Re[tau] =180 mais sans atteindre la relaminarisation. Nos résultats confirment que pour minimiser la traînée de l écoulement, il est plus efficace de considérer comme objectif l énergie cinétique que directement la traînée. Enfin, il est essentiel pour la convergence de la minimisation que le système optimal soit résolu sur un horizon temporel suffisamment longTwo control strategies were successively implemented to reduce the drag and the turbulent kinetic energy of a plane channel flow in turbulent regime (Re[tau]=180). Wall transpiration (unsteady blowing/suction) with zero net mass flux is used as the control. The main objective was to prove that a large eddy simulation (LES) could be relevant as a reduced-order model of the Navier-Stokes equations and thus strongly reduce the numerical costs. A heuristic approach known as opposition control was initially employed. The results show that the energetic efficiency is maximum for a position of the detection plane different from that which corresponds to the maximum of drag reduction. In addition, our results confirm that the drag reduction decreases with the increase of the Reynolds number. Then, an optimal control procedure was used by considering different cost functional (drag, terminal turbulent kinetic energy, mean turbulent kinetic energy). At Re[tau] =100, control managed to fully relaminarize the flow (drag reduction of about 50%) by considering as cost functional the terminal kinetic energy. For this same cost functional, an important drag reduction of about 55% is still obtained at Re[tau] =180 but without reaching the relaminarization. Our results show that to minimize the flow drag, it is more effective to consider the kinetic energy as cost functional than directly the drag. Lastly, it is essential for the convergence of the minimization that the optimality system is solved on a sufficiently long time horizonNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

1-[(E)-2-(5-tert-Butyl-2-hydroxyphenyl)diazen-1-yl]naphthalen-2-ol

The non-H atoms of the title compound, C20H20N2O2, is located on a mirror plane except two methyl groups of the tert-butyl group. Intramolecular N—H...O hydrogen bonds exist between the hydroxy and diazenyl groups. In the crystal, molecules are linked by weak C—H...O hydrogen bonds into supramolecular chains running along the a-axis direction