Milestones for Teaching the Spreadsheet Program

There are different manners of teaching a spreadsheet program. In any case, it is intended that the teacher settles the objectives of the course and adapts them to the particular audience he/she has to deal with. This paper aims at providing any teacher whatever his/her specific objectives and his/her audience with elements to help him/her building a course. It focuses mainly on two important issues: 1 - select in all that may be said about such complex tools, what is prior to know and to teach, i.e. what leads to autonomy in using but also to autonomy in learning (because everything cannot be taught) and 2 - show how concepts are closely related to good formatting considerations. A method based on the "invariants of information processing" is outlined, partially illustrated and an implementation is described throughout a course designed for students preparing a master in Education Sciences.Comment: 11 Page

Analyse de besoins pour un service en ligne

National audienceLe développement des formations totalement ou partiellement en ligne, ainsi que la mise à disposition de documents numériques pour les étudiants nécessitent de fournir des services innovants adaptés aux besoins induits. Nous nous intéressons ici aux étudiants qui effectuent tout ou partie de leur cursus dans une langue étrangère et qui rencontrent des difficultés dues à la langue. Notre objectif est de leur fournir, à la demande, en ligne et dans leur langue maternelle, un document similaire à celui qui fait difficulté pour eux. Nous présentons dans ce papier la phase d'analyse des besoins relative à l'ingénierie de ce service en ligne. Mots-clés. Ressources numériques de formation, fourniture de ressources dans une autre langue, service en ligne, analyse de besoins Abstract. The development of training fully or partially online, as well as the provision of digital materials for students, requires providing innovative services adapted to new needs identified. We focus on students who complete all or part of their course in a foreign language and who encounter difficulties due to language. Our goal is to provide on-demand, online and in their native language, a document similar to the one that troubles them. We present in this paper the needs analysis phase, relating to the engineering of this online servic

Needs analysis for an online learning service

International audienceThe development of fully or partially online training, as well as the provision of digital learning materials for students, requires the development of systems that provide students with innovative services tailored to their needs. We are interested in students who perform all or part of their course in a foreign language and who face difficulties due to language understanding. Our goal is to provide them, on demand, online and in their native language, with a document similar to the one that troubles them. In this paper we present the needs analysis phase, related to the engineering process of the online service

A Novel and Versatile Class of Coronavirus non-covalent Mpro Inhibitors based on 1,4,4-Trisubstituted Piperidines

This pilot study shows that a significant proportion of Long COVID-19 cases are positive for HERV-W ENV expression along with a subgroup of ME/CFS samples from a pre-COVID pandemia collection, raising the question of whether the presence of HERV-W ENV protein, known to induce TLR4-driven immuno- and neuro-pathogenicity, could be a common factor to their overlapping symptoms. Being this the case, HERV-W ENV could constitute a future therapeutic target, following the steps of other neurologic or autoimmune diseases such as multiple sclerosis or diabetes type I. Particularly since ongoing clinical trials assaying HERV-directional therapies based on antiretroviral agents or monoclonal antibodies are showing promising results.The COVID19 pandemia has greatly encouraged the development of vaccines and novel antivirals to control SARS-CoV-2 infection. Based on the promising anti-coronavirus activity observed for a class of anti-influenza H1N1 1,4,4-trisubstituted piperidines, developed in our goup, we performed a SAR analysis of these unique inhibitors that allowed to define the structural elements essential for antiHcoV-229E activity. Four of the best molecules were confirmed to be equally active against SARS-CoV-2. A TOA experiment indicated that these new CoV inhibitors interact at a post virus entry point lying at the stage of viral poly protein processing and the start of viral RNA synthesis. Enzymatic assays were performed with different CoV proteins involved in these processes. The compounds clearly inhibited the nsp5 main protease (Mpro). Although the inhibitory activity was modest, the ability to bind to the catalytic site of Mpro was assessed by in silico studies. The combination of results from TOA, enzymatic assays, resistance selection and in silico molecular modeling allowed us to conclude that the 1,4,4-trisubstituted piperidines represent a structurally novel and unique class of compounds that inhibit CoV Mpro inhibitors via a non-covalent mechanism, making these inhibitors fundamentally different from other Mpro inhibitors represented by the approved drug nirmatrelvir. The five points of diversity make these N-substituted piperidinebased compounds highly versatile and amenable to further rational optimization to maximize their activity and selectivity and gain full insight their antiviral mechanism.6th Innovative Approaches for Identification of Antiviral Agents Summer School September 26th-30th 2022, Santa Margherita di Pula, Sardinia, Ital

A Versatile Class of 1,4,4-Trisubstituted Piperidines Block Coronavirus Replication In Vitro

There is a clear need for novel antiviral concepts to control SARS-CoV-2 infection. Based on the promising anti-coronavirus activity observed for a class of 1,4,4-trisubstituted piperidines, we here conducted a detailed analysis of the structure–activity relationship of these structurally unique inhibitors. Despite the presence of five points of diversity, the synthesis of an extensive series of analogues was readily achieved by Ugi four-component reaction from commercially available reagents. After evaluating 63 analogues against human coronavirus 229E, four of the best molecules were selected and shown to have micromolar activity against SARS-CoV-2. Since the action point was situated post virus entry and lying at the stage of viral polyprotein processing and the start of RNA synthesis, enzymatic assays were performed with CoV proteins involved in these processes. While no inhibition was observed for SARS-CoV-2 nsp12-nsp7-nsp8 polymerase, nsp14 N7-methyltransferase and nsp16/nsp10 2’-O-methyltransferase, nor the nsp3 papain-like protease, the compounds clearly inhibited the nsp5 main protease (Mpro). Although the inhibitory activity was quite modest, the plausibility of binding to the catalytic site of Mpro was established by in silico studies. Therefore, the 1,4,4-trisubstituted piperidines appear to represent a novel class of non-covalent CoV Mpro inhibitors that warrants further optimization and development.This research was funded by grants from the Spanish MICINN (Projects PID2019-104070RB- C21 and PID2019-104070RB-C22); the Spanish Agencia Estatal Consejo Superior de Investigaciones Científicas (CSIC, Projects CSIC-PIE-201980E100 and CSIC-PIE-201980E028); the European Union’s Innovative Medicines Initiative (IMI) under Grant Agreement 101005077 [Corona Accelerated R&D in Europe (CARE) project]; and Fundació La Marató de TV3, Spain (Projects No. 201832-30 and No. 202135-30). B.V.L. holds an SB-PhD fellowship from the FWO Research Foundation Flanders (project: 1S66321N)Peer reviewe

Concerted Regulation of cGMP and cAMP Phosphodiesterases in Early Cardiac Hypertrophy Induced by Angiotensin II

Left ventricular hypertrophy leads to heart failure and represents a high risk leading to premature death. Cyclic nucleotides (cAMP and cGMP) play a major role in heart contractility and cyclic nucleotide phosphodiesterases (PDEs) are involved in different stages of advanced cardiac diseases. We have investigated their contributions in the very initial stages of left ventricular hypertrophy development. Wistar male rats were treated over two weeks by chronic infusion of angiotensin II using osmotic mini-pumps. Left cardiac ventricles were used as total homogenates for analysis. PDE1 to PDE5 specific activities and protein and mRNA expressions were explored