Les pratiques enseignantes pour un enseignement sans stéréotypes de genre en 1-2H :: choix des jouets, ressources et actions des enseignant·e·s

Afin de s’orienter vers un système éducatif plus égalitaire, une sensibilisation dès le plus jeune âge aux stéréotypes de genre est à préconiser. C’est effectivement l’intérêt de ce mémoire, qui s’intéresse à un thème particulièrement d’actualité, car il concerne l’égalité entre filles et garçons à l’école. Ce travail s’articule autour de lectures scientifiques ainsi que d’un travail de recherche dans les écoles, avec notamment la rencontre d’enseignant·e·s titulaires de classes de première et deuxième HarmoS, dans lesquelles les stéréotypes de genre sont particulièrement présents. L’étude permet d’une part de mettre en exergue le rôle primordial de l’enseignant·e dans la lutte des stéréotypes de genre à l’école qui est notamment celui de prévenir la création de stéréotypes et de développer le sens critique des élèves, leur permettant ainsi de les reconnaître. D’autre part, elle décrit les pratiques des enseignant·e·s, leurs ressources et leurs actions pour un enseignement basé sur l’égalité des sexes. Ce travail étudie également les critères de choix des jouets des personnes interviewées, ces derniers pouvant être un transmetteur de stéréotypes de genre ou inversement, un moyen de les contrecarrer pour autant qu’ils s’orientent vers une certaine neutralité

Survival after bilateral breast cancer: results from a population-based study

Background: Controversy exists on the impact of bilaterality of breast cancer on survival. We used population-based data to compare survival of women with unilateral versus bilateral breast cancer. Patients and methods: At the Geneva cancer registry, we identified all 7,912 women diagnosed with invasive breast cancer between 1970 and 2002. Breast cancers were categorized as unilateral, synchronous bilateral (contralateral tumour diagnosed within six months after the first tumour) and metachronous bilateral (contralateral tumour diagnosed over six months after the first tumour). With multivariate modelling we compared characteristics and survival between women with unilateral and bilateral disease. Results: Patients with synchronous bilateral tumours (n=155, 2.0%) had more often lobular histology and less frequently stage I disease than women with unilateral disease. Women with metachronous breast cancer (n=219, 2.8%) received less often chemotherapy or hormone therapy for their first tumours. Ten-year disease-specific survival was similar (66%) after unilateral and metachronous bilateral breast cancer, but worse after synchronous bilateral cancer (51%). After adjustment, breast cancer mortality risks were not significantly increased for women with either synchronous or metachronous bilateral disease (Hazard ratios 1.1 (0.8-1.5) and 0.8 (0.5-1.4), respectively). Conclusion: This large population-based study indicates that bilaterality of breast cancer is not associated with impaired surviva

Development of (6 R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5 H-imidazo[2,1- b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis.

Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3-dihydroimidazo[2,1- b][1,3]oxazoles and 7-substituted 2-nitro-5,6-dihydroimidazo[2,1- b][1,3]oxazines stimulated the examination of further scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1- b][1,3]oxazepines), but the results for these seemed less attractive. Following the screening of a 900-compound pretomanid analogue library, several hits with more suitable potency, solubility, and microsomal stability were identified, and the superior efficacy of newly synthesized 6 R enantiomers with phenylpyridine-based side chains was established through head-to-head assessments in a Leishmania donovani mouse model. Two such leads ( R-84 and R-89) displayed promising activity in the more stringent Leishmania infantum hamster model but were unexpectedly found to be potent inhibitors of hERG. An extensive structure-activity relationship investigation pinpointed two compounds ( R-6 and pyridine R-136) with better solubility and pharmacokinetic properties that also provided excellent oral efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6 as the favored backup development candidate

DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.</p

DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis.</p

DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1.

New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field are urgently required. Despite concerted efforts over the last several years, the number of new chemical entities that are suitable for clinical development for the treatment of Leishmania remains low. Here, we describe the discovery and preclinical development of DNDI-6174, an inhibitor of Leishmania cytochrome bc1 complex activity that originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required for progression into preclinical development. In addition to good metabolic stability and pharmacokinetic properties, DNDI-6174 demonstrates potent in vitro activity against a variety of Leishmania species and can reduce parasite burden in animal models of infection, with the potential to approach sterile cure. No major flags were identified in preliminary safety studies, including an exploratory 14-day toxicology study in the rat. DNDI-6174 is a cytochrome bc1 complex inhibitor with acceptable development properties to enter preclinical development for visceral leishmaniasis

Contributions à la théorie des matroïdes : polytope des bases, orientations et algorithmes

In chapter 2, we study a special decomposition intoduced by Lafforgue. More precisely, let P(M) be the matroid base polytope of a matroid M. A matroid base polytope decomposition of P(M) is a decomposition of the form P(M) = St i=1 P(Mi) where each P(Mi) is also a matroid base polytope for some matroid Mi, and for each 1 i 6= j t, the intersection P(Mi)\P(Mj) is a face of both P(Mi) and P(Mj). In this thesis, we investigate hyperplane splits, that is, polytope decompositions when t = 2. We give sufficient conditions for M so P(M) has a hyperplane split and characterize when P(M1 M2) has a hyperplane split where M1 M2 denote the direct sum of matroids M1 and M2. We also prove that P(M) has not a hyperplane split if M is binary. Finally, we show that P(M) has not a decomposition if its 1-skeleton is the hypercube. In chapitre 3 we investigate the class of lattice oriented matroids. After giving a complete characterization of lattice oriented matroids in terms of union of rank-1 uniform oriented matroids, we show that this class is closed under duality and minors. We then study the simplexes of the hyperplane arrangements arising from lattice oriented matroids. We present a characterization of these simplexes and contruct arrangements of n hyperplanes in dimension d containing O(2k(n k )k) simplexes with n < k = bd 2 c. We finally investigate a question by Grünbaum [Grünbaum, 1971] concerning colorings of pseudoline arrangements. We extend Grünbaum's question to arrangements of hyperplanes and answer affirmatively the generalized question for arrangements arising from lattice oriented matroids. In chapitre 4 we are interested in an oriented matroid version of the well-known Shannon's switching game introduced by Hamidoune and Las Vergnas[Hamidoune et Las Vergnas, 1997a] in 1986. They conjectured that the classification of the directed switching game on an oriented matroids is identical to the classification of non-oriented version. In this thesis, we support this conjecture by showing its validity for an infinity class of oriented matroids obtained as unions of rank-1 and/or rank-2 uniform oriented matroids.Dans cette thèse on étudie différents problèmes portant sur les matroïdes et les matroïdes orientés. On s'intéresse à trois sujets particuliers : la décomposition du polytope des bases d'un matroïde, l'orientation de matroïdes et le jeu de commutation de Shannon. Plus précisément dans le chapitre 2 nous étudions une décomposition spéciale introduite par Lafforgue. Pour un matroïde M, une décomposition du polytope des bases d'un matroïde P(M) est une décomposition de la forme P(M) = St i=1 P(Mi) où chaque P(Mi) est également un polytope des bases d'un matroïde pour un certain matroïde Mi, et pour chaque 1 i 6= j t, l'intersection P(Mi) \ P(Mj) est une face de P(Mi) et de P(Mj). Dans cette thèse, nous étudions la séparation par hyperplan, autrement dit la décomposition du polytope quand t = 2. Nous donnons des conditions suffisantes sur M pour que P(M) puisse avoir une séparation par hyperplan. Nous caractérisons également les cas où P(M1 M2) a une séparation par hyperplan où M1 M2 dénote la somme directe des matroïdes M1 et M2. Nous montrons finalement que P(M) n'a pas de séparation par hyperplan si M est binaire. Dans le chapitre 3 nous étudions la classe des matroïdes orientés du réseau. Après avoir donné une caractérisation complète des matroïdes orientés du réseau en fonction de l'union de matroïdes orientés uniformes de rang un, nous montrons que cette classe est fermée par dualité et par mineurs. Nous étudions ensuite les simplexes de l'arrangement d'hyperplans découlant de matroïdes orientés du réseau. Nous présentons une caractérisation de ces simplexes et construisons un arrangement de n hyperplans en dimension d contenant O(2k(n k )k) simplexes avec n < k = bd 2 c. Nous approfondissons une question posée par Grünbaum [Grünbaum, 1971] concernant les colorations des arrangements de pseudodroites. Nous prolongeons la question de Grünbaum à des arrangements d'hyperplans et répondons par l'affirmative à cette question généralisée pour les arrangements découlants de matroïdes orientés du réseau. Dans le chapitre 4 nous nous sommes intéressés à une une version sur les matroïdes orientés du célèbre jeu de commutation de Shannon, version introduite par Y.O. Hamidoune et M.Las Vergnas[Hamidoune et Las Vergnas, 1997a] en 1986. Ils ont conjecturé que la classification du jeu de commutation sur les matroïdes orientés est identique à la classification de la version non orientée. Dans cette thèse, nous confortons cette conjecture en montrant sa validité pour la classe infinie de matroïdes orientés obtenues comme union de matroïdes orientés uniformes de rang 1 et/ou de rang 2

THE SWITCHING GAME ON UNIONS OF ORIENTED MATROIDS

In 1986, Hamidoune and Las Vergnas [3] introduced an oriented matroid version of the so-called Shannon’s switching game. They conjectured that the classification of the directed switching game on oriented matroids is identical to the classification of the non-oriented version. In this note, we support this conjecture by showing its validity for an infinity class of oriented matroids obtained as unions of rank-1 and/or rank-2 uniform oriented matroids

Matroid base polytope decomposition II: sequences of hyperplane splits

International audienceThis is a continuation of an early paper [Adv. Appl. Math. 47(2011), 158-172] about matroid base polytope decomposition. We will present sufficient conditions on a matroid M so its base polytope P (M) has a sequence of hyperplane splits. These yield to decompositions of P (M) with two or more pieces for infinitely many matroids M. We also present necessary conditions on the Euclidean representation of rank three matroids M for the existence of decompositions of P (M) into 2 or 3 pieces. Finally, we prove that P (M1 ⊕ M2) has a sequence of hyperplane splits if either P (M1) or P (M2) also has a sequence of hyperplane splits