Doing mathematics with the APLUSIX-Editor

International audienceThe APLUSIX-Editor is a microworld dedicated to the learning of algebra. First it includes an advanced editor that allows the student to build easily algebraic expressions. Second it reifies the student's reasoning as a linear development of equivalent steps or as a tree. Third it verifies the equivalence between the different steps during student's calculations, and gives indications about the progression of the reasoning. The first three parts of the paper present the syntactical aspect, the semantic aspect and the strategic aspect of the APLUSIX-Editor. The last parts present experiments conducted with the APLUSIX-Editor

Identification de facteurs génétiques impliqués dans les troubles du spectre autistique et de la dyslexie

Les troubles du spectre autistique (TSA) touchent approximativement 1% de la population générale. Ces troubles se caractérisent par un déficit de la communication sociale, ainsi que des comportements stéréotypés et des intérêts restreints. Plusieurs gènes impliqués dans le déterminisme des TSA ont été identifiés, comme par exemple les gènes NLGN3-4X, NRXN1-3 et SHANK1-3. Au cours des années précédentes, les TSA ont été considérés comme un ensemble complexe de troubles monogéniques. Cependant, les études récentes du génome complet suggèrent la présence de gènes modificateurs ( multiple hits model ). La dyslexie est caractérisée par un trouble dans l apprentissage de la lecture et de l écriture qui touche 5- 15% de la population générale. Les facteurs génétiques impliqués restent pour l instant inconnus car seuls des gènes ou loci candidats ont été identifiés. Mon projet de thèse avait pour objectif de poursuivre l identification des facteurs génétiques impliqués dans les TSA et de découvrir un premier facteur génétique pour la dyslexie. Pour cela, deux types de populations ont été étudiés : d une part des patients atteints de TSA (N>600) provenant de France, de Suède et des Iles Faroe, d autre part des patients atteints de dyslexie (N>200) provenant de France, en particulier une famille de 11 personnes atteintes sur 3 générations. J ai utilisé à la fois la technologie des puces à ADN Illumina (600 K et 5M) et le séquençage complet du génome humain pour effectuer des analyses de liaison et d association. Pour les TSA, grâce aux analyses de CNVs, j ai pu identifier des gènes candidats pour l autisme et confirmer l association de plusieurs gènes synaptiques avec l autisme. En particulier, l étude d une population de 30 patients des îles Faroe a pu confirmer l implication des gènes NLGN1 et NRXN1 dans l autisme et identifier un nouveau gène candidat IQSEC3. En parallèle, j ai exploréPRRT2 localisé en 16p11.2. PRRT2 code pour un membre du complexe SNARE synaptique qui permet la libération des vésicules synaptiques. Je n ai pas pu mettre en évidence d association avec les TSA, mais j ai montré que ce gène important pour certaines maladies neurologiques était sous pression de sélection différente selon les populations. Pour la dyslexie, j ai effectué une analyse de liaison (méthode des lod-scores) pour une grande famille de 11 individus atteints sur trois générations. Cette étude a permis d identifier CNTNAP2 comme un gène de vulnérabilité à la dyslexie. Cette découverte est importante car ce même gène est aussi associé aux TSA. Par contre, aucune des 20 variations rares découvertes par le séquençage complet du génome n est localisée dans les parties codantes du gène. Plusieurs variations localisées dans des régions régulatrices sont candidates. En conclusion, les résultats de ma thèse ont permis d identifier des gènes candidats pour les TSA, de confirmer le rôle des gènes synaptiques dans ce trouble, de montrer pour la première fois grâce à une analyse de liaison le rôle de CNTNAP2 dans la dyslexie.Autism spectrum disorders (ASD) affect 1% of the general population. These disorders are characterized by deficits in social communication as well as stereotyped behaviors and restricted interests. Several genes involved in the determination of ASD have been identified, such as NLGN3-4, NRXN1-3 and SHANK1-3. In the previous years, ASD have been considered as a complex set of monogenic disorders. Recent studies on the complete genome nevertheless suggest the presence of modifier genes ("multiple hits model"). Dyslexia is characterized by difficulties in learning to read and write. It affects 5-15 % of the general population. Genetic factors involved remain unknown. Only candidate genes or loci have been identified. My thesis had two main objectives: pursuing the identification of genetic factors involved in ASD, and discovering a first genetic factor for dyslexia. I therefore studied two types of populations: on the one hand a group of patients with ASD (N > 600) from France, Sweden and the Faroe Islands, and on the other hand another group of patients with dyslexia (N > 200) from France, and more specifically a family of 11 people followed over 3 generations. I used both Illumina microarrays technology (600K and 5M) and the complete human genome sequencing to conduct linkage and association analyses. Regarding ASD, CNVs (copy number variants) analyses allowed me to confirm the association of several synaptic genes with autism and to identify new candidate genes. In particular, the study of a population of 30 patients from the Faroe Islands confirmed the involvement of NLGN1 and NRXN1 genes in autism and identified a new candidate gene, IQSEC3. At the same time, I explored PRRT2 located in 16p11.2. PRRT2 encodes a member of the synaptic SNARE complex that allows the release of synaptic vesicles. I have not been able to demonstrate any association with ASD, but I showed that this gene, which is important for some neurological diseases, was under different selection pressures according to the population considered. Regarding dyslexia, I realized a linkage analysis (lod-score method) for a large family of 11 individuals, with three generations affected. This study identified the CNTNAP2 gene as a vulnerability factor for dyslexia. This finding is important because this gene is also associated with ASD. Nevertheless, none of the 20 rare variations discovered by whole genome sequencing is localized in the coding parts of the gene. Only several variations localized in regulatory regions are robust candidates. To conclude, my findings enabled the identification of new candidate genes for ASD, the confirmation of the role of synaptic genes in this disorder, and the highlight for the first time of the role of CNTNAP2 in dyslexia through linkage analysis.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Aix-en-Provence – ZAC Sextius-Mirabeau, secteur Pompidou

Identifiant de l'opération archéologique : 7775 Date de l'opération : 2007 (SP) Inventeur(s) : Copetti Audrey (COL) ; Huguet Céline (COL) ; Navarro Thomas (COL) ; Portalier Nicolas (COL) Dernières opérations du programme d’aménagement de la ZAC Sextius-Mirabeau, la création de la future voie Georges-Pompidou et la construction de deux immeubles ont donné lieu à un diagnostic conduit en 2005 par Robert Thernot de l’INRAP (BSR PACA, 2005 : 109-110), et à une fouille préventive qui a été réalisé..

Impact of climate change on the ecology of the Kyambangunguru crater marsh in southwestern Tanzania during the Late Holocene

Instrumental records of temperature and hydrological regimes in East Africa evidence frequent droughts with dramatic effects on population and ecosystems. Sources of these climatic variations remain largely unconstrained, partly because of a paucity of Late Holocene records. Here, we present a multi-proxy analysis of a 4-m continuous sediment core collected in the Kyambangunguru crater marsh, in southwest Tanzania, covering the last 4000 yrs (cal. BP). We used microscopic (macro-remains, microfossils, palynofacies, pollen), elemental (carbon, nitrogen contents), molecular (br GDGTs, n-alkanes) and compound-specific isotopic (δ2H n-alkanes) investigations to reconstruct the environmental history of the marsh. The multi proxy record reveals that, 2500 years ago, the marsh underwent a major ecological transition from a lake to a peatland. Temperature and hydrological reconstructions evidence warmer and drier conditions between 2200 and 860 cal. BP, which probably triggered the establishment of a perennial peatland. This study is one of the first combined temperature and precipitation record of Late Holocene in the region and highlights changes in the spatial distribution of the East African climate regimes. Several cold periods are observed, between 3300 and 2000 cal. BP and since 630 cal. BP, the latter corresponding to the Little Ice Age. Moreover, wetter conditions are reported during the Medieval Climate Anomaly in contrast to other north-eastern African records suggesting that Tanzania is located at the transition between two hydro-climatic zones (north-eastern versus southern Africa) and has experienced variable contributions of these two zones over the last millennium

Signatures for a Cosmic Flux of Magnetic Monopoles

Any early universe phase transition occurring after inflation has the potential to populate the universe with relic magnetic monopoles. Observations of galactic magnetic fields, as well as observations matched with models for extragalactic magnetic fields, lead to the conclusion that monopoles of mass \lsim 10^{15} GeV are accelerated in these fields to relativistic velocities. We explore the possible signatures of a cosmic flux of relativistic monopoles impinging on the earth. The electromagnetically-induced signatures of monopoles are reliable. The hadronically-induced signatures are highly model-dependent. Among our findings are (i) the electromagnetic energy losses of monopoles continuously initiate a protracted shower of small intensity; (ii) monopoles may traverse the earth's diameter, making them a probe of the earth's interior structure; (iii) in addition to the direct monopole Cherenkov signal presently employed, a very attractive search strategy for monopoles is detection of their radio-Cherenkov signal produced by the coherent charge-excess in the $e^+-e^-$ shower - in fact, Cherenkov-detectors have the potential to discover a monopole flux (or limit it) several orders of magnitude below the theoretical Parker limit of $10^{-15}/\rm{cm}^2$/s/sr; (iv) it is conceivable (but not compelling) that bound states of colored monopoles may be the primary particles initiating the air showers observed above the GZK cutoff.Comment: 33 pages, 5 figures, revtex, to appear in Astro. Part. Phy

Evaluation of branched GDGTs and leaf wax n-alkane δ2H as (paleo) environmental proxies in East Africa

The role of mountain evolution on local climate is poorly understood and potentially underestimated in climate models. One prominent example is East Africa, which underwent major geodynamic changes with the onset of the East African Rift System (EARS) more than 250 Myr ago. This study explores, at the regional East African scale, a molecular approach for terrestrially-based paleo-climatic reconstructions that takes into account both changes in temperature and in altitude, potentially leading to an improved concept in paleo-climatic reconstructions. Using surface soils collected along pronounced altitudinal gradients in Mt. Rungwe (n=40; Southwest Tanzania) and Mt. Kenya (n=20; Central Kenya), we investigate the combination of 2 terrestrial proxies, leaf wax n-alkane δ2H (δ2Hwax) and branched glycerol dialkyl glycerol tetraether (br GDGT) membrane lipids, as (paleo) elevation and (paleo) temperature proxies, respectively. At the mountain scale, a weak link between δ2Hwax and altitude (R2 = 0.33) is observed at Mt. Kenya, but no relationship is observed at Mt. Rungwe. It is likely that additional parameters, such as decreasing relative humidity (RH) or vegetation changes with altitude, are outcompeting the expected 2H-depletion trend along Mt. Rungwe. In contrast, br GDGT-derived absolute mean annual air temperature (MAAT) and temperature lapse rate (0.65 °C/100 m) for both mountains are in good agreement with direct field measurements, further supporting the robustness of this molecular proxy for (paleo) temperature reconstructions. At the regional scale, estimated and observed δ2H data in precipitation along 3 mountains in East Africa (Mts. Rungwe, Kenya and Kilimanjaro) highlight a strong spatial heterogeneity, preventing the establishment of a regional based calibration of δ2Hwax for paeloaltitudinal reconstructions. Different from that, an improved regional soil calibration is developed between br GDGT distribution and MAAT by combining the data from this study (Mts. Rungwe and Kenya) with previous results from East African surface soils along Mts. Kilimanjaro (Tanzania) and Rwenzori (Uganda). This new regional calibration, based on 105 samples, improves both the R2 (0.77) and RMSE (root mean square error; 2.4 °C) of br GDGT-derived MAAT over the global soil calibrations previously established (R2 = 0.56; RMSE = 4.2 °C) and leads to more accurate (paleo) temperature reconstructions in the region