Dans un contexte d'interdépendance des États, le besoin d'une action commune pour sauvegarder l'environnement se fait ressentir au regard des risques qui pèsent sur la société internationale. Notion à dimension politique et morale, les responsabilités communes mais différenciées ont été conçues pour répondre à cette nécessité en aménageant une différenciation entre les États en fonction de leur niveau de développement. Bien qu'elles instaurent une dualité normative, elles se distinguent de la différenciation classique par leurs aspects développementaux et prospectifs. Depuis l'Accord de Paris du 12 décembre 2015, elles ont vu leur place renforcée dans le régime climat. Principe protéiforme, directeur et structurant, les responsabilités communes mais différenciées participent aux efforts d'humanisation du droit international. La présente thèse entend contribuer à l'étude de leur structuration comme principe général du droit international de l'environnement dont l'effectivité sera vérifiée dans le régime juridique applicable aux activités climatiques. / In a contexte of increasing interdependance among States, and regarding the risks for the international society, a joint action is required in order to protect the environment. Including both political and moral dimensions, the common but differentiated responsibilities have been designed to set a differentiation between States based on their level of development. Although they institute a normative duality, they are distinguished from classical differentiation due to their development and prospective aspects. The notion of common but differentiated responsibilities has been strengthened in the framework of the climate regime since the Paris Agreement 2015. As a protean, director and structuring principle, the common but differentiated responsibilities participates in humanising international law. This PhD dissertation aims to contribute to the structuration of the common but differentiated responsibilities as a general principle of international environmental law. Their scope will be examined through an assessment of their effectiveness within the climate regime framework.

Les différences de réponse médicamenteuse entre patients sont fréquentes, conduisant souvent à des difficultés à cibler la fenêtre thérapeutique et optimiser le traitement. Les médicaments courants sont efficaces pour seulement 25% à 60% des patients. Deux facteurs majeurs impliqués dans l’efficacité des médicaments sont leur métabolisme et clairance. Notamment, le CYP3A4 est la principale enzyme responsable du métabolisme des médicaments dans les hépatocytes ; des variations dans son activité entraînent une incertitude de dose. Pour améliorer l'efficacité du médicament, ce travail de thèse se concentre sur le développement de nano-transporteurs chargés avec des molécules naturelles inhibant le CYP3A4 et ciblant les hépatocytes, à administrer avant le médicament pour minimiser son métabolisme. Une méthodologie pour examiner les composés inhibiteurs du CYP3A4, fixer leur dose et leur temps d’administration pour une utilisation in vivo a été développée. Une première preuve de concept a été démontrée en utilisant une micelle chargée de furanocoumarine comme composé inhibiteur de CYP3A4 : des études d'efficacité antitumorale et la quantification dans la tumeur du médicament cytotoxique docetaxel, injecté après les micelles chargées de furanocoumarine, ont été engagés sur deux modèles de tumeurs xénogreffées chez la souris. Une deuxième génération de nano-transporteurs a été développée, avec des propriétés physico-chimiques optimisées pour cibler spécifiquement les hépatocytes. La démonstration de leur accumulation spécifique dans les hépatocytes et de l'amélioration supplémentaire de l’efficacité du docetaxel a été menée. Une perspective sur l'utilisation d'une telle approche pour améliorer l'efficacité des médicaments existants en oncologie est discutée, notamment pour le carcinome hépatocellulaire différencié. / Differences in drug response among patients are common, often leading to challenges in targeting the therapeutic window and optimizing the treatment. Major drugs are reported to be effective in only 25% to 60% of patients. Two important factors responsible for the effective dose of drug are drug metabolism and clearance. Notably, CYP3A4 is the main enzyme responsible for drug metabolism in hepatocytes; variations in its activity result in dose uncertainty. To improve drug’s effectiveness, this thesis work focuses on the development of nanocarriers loaded with natural CYP3A4-inhibiting molecules and targeting hepatocytes, to be administered prior to the drug to minimize its metabolism. A methodology to systematically screen CYP3A4-inhibiting compounds and set the dose and schedule for in vivo use was developed. A first proof-of-concept was demonstrated using a furanocoumarin-loaded micelle as CYP3A4-inhibiting compound: anti-tumor efficacy studies and quantification within tumor of the cytotoxic drug docetaxel, injected after furanocoumarin-loaded micelle, were engaged on two xenografted tumor models in mice. A second generation of nanocarriers was developed, with optimised physico-chemical properties to target specifically hepatocytes. The demonstration of their specific accumulation in hepatocytes and additional improvement in boosting of docetaxel was conducted. A perspective in using such an approach to enhance the effectiveness of existing drugs in oncology is discussed, notably for differentiated hepatocellular carcinoma.

Educators are challenged with meeting the academic needs of students, particularly in the subject area of reading. School districts purchase tools such as Achieve3000 to help students improve their proficiency in reading; however, implementation of such interventions has not been explored from the educators' perspective. This study explored 3rd grade reading teachers' views on Achieve3000 as a tool for improving reading proficiency and preparedness for the Florida State Standards English Language Arts assessment. The conceptual framework included the theory of social validity and current research as it related to differentiated instruction. This study utilized a basic qualitative approach to answer these key research questions. The participants included 6 3rd grade reading teachers from 3 Florida schools. Individual face-to-face interviews and a focus group interview session were conducted to answer the research questions. Data were analyzed via open, axial, and selective coding to generate the themes. The findings revealed the 3rd grade reading teachers believed that Achieve3000 can be considered a reliable method for improving reading and preparing students for the reading portion of the Florida Standards Assessment. The findings of this study can positively affect social change by providing educators with an increased repertoire of instructional tools to assist them in meeting the needs of all learners, as well as to prepare students for a technology driven world.

The introduction of the European Union (EU) macro-regional strategies (MRS) in the latter half of the 2000s was a significant step in the process of transformation of EU governance system. EU MRSs act as a new form of comprehensive governance framework for multi-objective and cross-sectoral cooperation in geographically defined macro-regions. This thesis examines the case of the Baltic Sea Region in order to evaluate a potential of this new governance instrument to transform cooperation arrangements in the region. In order to shed light on the strategy’s patterns and dynamics, the present study utilizes a qualitative methodological approach that uses document analysis based on a comprehensive analytical framework. The analytical framework incorporates the theoretical perspectives of multi-level and experimentalist governance, as well as the theory of differentiated integration. The main findings of this study suggest that the inception of the EU Strategy for the Baltic Sea Region (EUSBSR) in 2009 has offered an innovative and dynamic framework for cooperation that enabled a wider representation and more active participation of local and regional actors. This allowed for a more coherent and coordinated policymaking, facilitated a more responsive and transparent cooperation system in the region, as well as fostered transnational cooperation in the Baltic Sea Region by ensuring a wider engagement of non-EU countries.

In this paper, creative mathematical activities of school pupils in conditions of the differentiated teaching in Russian Federation are described. Various forms of differentiated teaching (internal – level, external – profile) are characterized. Ways of using entertaining problems for detecting and fostering mathematical abilities are revealed. New course of geometry for differentiated teaching is introduced.

In an urban Title 1 school district, the average number of Grade 3-5 students who scored proficient or advanced on the state standardized assessment was 37.3% below Grade 3-5 students countywide and 19.4% below Grade 3-5 students statewide. Low mathematics scores may indicate a gap in practice that affects student achievement. The purpose of this descriptive case study was to examine teachers' descriptions of instructional strategies implemented to mediate instruction for students who struggle in mathematics. This study was based on the conceptual framework of Tomlinson's differentiated instruction (DI), a means of accommodating the varied ways that students learn. The research questions guided an inquiry into how teachers of students in Grades 3-5 in the school district described DI in practice and explained their professional development on DI strategies. Data were collected from individual interviews with 8 elementary school teachers of students in Grades 3-5 and an instructional coach in the local school district with 3 or more years of experience who considered themselves knowledgeable of DI. I coded the meaningful data collected from the interviews and subsequently formed themes. Themes that emerged from the interviews included defining DI, tools for instruction, classroom set-up and transitioning, assessments, professional development, and grouping strategies. Results revealed that interviewees were confident in defining and facilitating DI grouping strategies for English and language arts but felt the need for more professional development to implement and understand DI in relation to mathematics. The study outcome may impact social change by affecting the gap in practice through professional development that helps teachers implement DI strategies in the classroom to improve student achievement in mathematics.

Optical networks employing wavelength division multiplexing technology have been well recognized as the core networks for the next generation Internet. In such networks, any fiber cut or node failure may lead to huge data loss. Thus, reliability is of great importance in the design of modern high-speed networks. At the same time, traffic grooming is another important design objective since it addresses multi-granularity traffic. The traditional routing approaches with differentiated services do not consider the traffic grooming case or reconfiguration method. Therefore, they are not resource-efficient for the next generation Internet. In this dissertation, an effective reconfigurable traffic grooming with differentiated reliability scheme is proposed to efficiently use network resources. Compared with the conventional rerouting method, the proposed scheme makes the network more robust and immune from service interruptions. An integer linear programming (ILP) formulation is presented first. By solving the ILP formulation, an optimal solution is obtained for each incoming connection request. However, the solution is so time consuming, a heuristic algorithm is introduced to get an approximate optimal solution. The performance evaluation indicates that the connection blocking probability can be decreased greatly by the proposed scheme.

The purpose of this study was to explore the relationship between the use of a computer-managed integrated learning system entitled Accelerated Math (AM) as a supplement to traditional mathematics instruction on achievement as measured by TerraNova achievement tests of third and fourth grade high-ability students. Gender, socioeconomic status, and grade level were also considered. The population consisted of 624 students who were third and fourth grade high-ability students during the 2009-2010 school year. Data were gathered that covered a 1-year period for high-ability third and fourth graders. A series of independent samples t-tests were used to identify relationship among variables. The researcher's investigation of the relationship between AM and mathematics achievement might assist educators in planning for use of technology as a supplement to the normal mathematics curriculum. The findings indicated measurable differences in the performance of high-ability third and fourth grade students who qualified for free and reduced priced lunch and participated in AM compared to high-ability students who qualified for free and reduced priced lunch and did not participate in the program. High-ability students who participated in the AM program and who qualified for free and reduced lunch scored significantly higher on the TerraNova math achievement test than students who did not participate in AM and who qualified for free and reduced lunch. There were also measurable differences in the performance of high-ability fourth grade students who participated in the AM program compared to those who did not participate in the program. Fourth grade high-ability students who participated in the AM program scored significantly higher on the TerraNova math achievement test than fourth grade students who did not participate in the program. This study indicated no significant findings among gender, students in grade 3, and students who did not qualify for free and reduced price lunch who did and did not participate in the AM program.

In a previous paper, we analyzed accidents of pedelec riders in 2019 and examined possible changes over the past years. We found that pedelec accidents still essentially resemble the classic two-wheeler accident characteristics, with certain specifics (e.g., higher age of riders involved in an accident, higher proportion of single-bicycle accidents, higher proportion of out-of-town accidents). Even though the number of pedelecs and pedelec accidents has increased in recent years, no qualitative changes in the characteristics of accidents compared to previous years seem to have occurred. We now have a large data base of riders and accidents and new data sources that offer the possibility for calculating accident risks by mileage-based analyses. In addition to absolute accident numbers, relative accident parameters are of particular interest for accident research and prevention. Using the same amount of physical effort pedelecs can be used to cover longer distances than bicycles. At the same time, longer distances increase the probability of being involved in an accident. On average, pedelec users cover 1.8 times as many kilometers per day as bicycle users do. We now have nationally representative data on the mileage of pedelec riders, so we can calculate mileage-based accident risks and get new insight into pedelec accidents. For comparison the accident risks of bicycle riders are used.

The Republic of Kosovo’s self-declared multiethnic society has strived to construct an inclusive attitude and tolerating spirit toward all communities within. This study has explored how group-differentiated rights are used to construct identity and multiethnicity in relation to European integration in four official documents using the research questions; how is the production of identity and multiethnicity through group-differentiated rights in Kosovo constructed in the documents and related to EU integration; and how has the EU accession process affected the construction of multiethnicity and identity in Kosovo’s documents on minorities relating to group-differentiated rights? An ethnographic content analysis and comparative design, with a social constructivist perspective, grasping the constituents of group-differentiated rights concerning exclusive rights granted to minorities employed to develop, and safeguard identities was applied. The key findings have demonstrated that the development of group-differentiated rights through multiethnicity and identity relating to EU accession and integration may be considered mutually constitutive, creating a path for Kosovo's future EU membership and a sustainable multiethnic society founded on democracy and the rule of law. Although, Kosovo has demonstrated a readiness to adjust and adhere to EU directives, adequate implementation of minority and human rights is the first and primary step toward EU membership.