This study evaluates, through history and analysis, the value of extradition as a method of combating international terrorism during the past two decades, from the perspective of the U. S. experience. Through the adoption of an integrated framework, a case study approach is applied with the intention of illuminating major themes and issues relevant to state response and terrorist extradition, while exposing several underlying themes about the political relationship between extradition and terrorism. Historical analysis demonstrates that current methods of rendering fugitive terrorists are not just the simple application of international rules, but an evolving process of law. Alternatives to the use of extradition are also examined, with particular reference to state sponsored terrorism, their impact on extradition, the prospects for military retaliation, and the potential for alternatives such as an International Criminal Court. The evolving nature of terrorist extradition is examined in concert with the changing nature of terrorism itself, and how ultimately this influences not only the law, but also law enforcement. By utilising such an approach, the study seeks to extricate the fundamental issues behind U.S. extradition policy, and ultimately the usefulness of extradition as a tool against terrorism.

The methods of molecular quantum mechanics have been used to study the important biological molecules glutathione, ascorbic acid and related compounds. The preferred conformations of glutathione, its constituent amino acids and their residues have been investigated using the semi-empirical PCILO procedure. Comparisons with ab initio calculations are given for the smaller molecules. The electronic structure and properties of ascorbic acid and its metabolites have been studied using ab initio procedures. The calculations include geometry optimizations, electrostatic molecular potential maps, spin density calculations on the radical species and investigations of charge transfer interactions and of metal complexing.

Les papillomavirus à « haut risque » (HR) sont les agents étiologiques du cancer du col de l’utérus. Les vaccins prophylactiques actuels assurent une protection contre les lésions induites par les génotypes 16 et 18, responsables de 70% de ces cancers. Les lésions induites par les treize autres HPV HR responsables de 30% des cancers ne sont potentiellement pas prévenues par ces vaccins. Les objectifs de ma thèse ont été d’évaluer la capacité du vaccin quadrivalent anti-HPV et des vaccins de seconde génération à induire une immunité cross-neutralisante contre les HPV HR. Tout d’abord, la capacité du vaccin quadrivalent anti-HPV à induire des anticorps neutralisant les HPV 31 et 58 a été analysée. L’induction d’anticorps neutralisant les HPV 31 et 58 a été mise en évidence, 1 mois après la dernière injection, chez 33% et 24% des femmes vaccinées, respectivement. Les pseudovirions (PsV) de l'HPV 58 produits en système cellulaire et utilisés pour cette étude présentent une capacité de transduction des cellules COS-7 10 fois supérieure à celle des PsV 31 et représente un vecteur de choix pour des applications en immunisation génique. La deuxième partie de ma thèse s’est orientée sur le développement et l’analyse de la réponse immune induite par des vaccins de seconde génération basés sur la protéine L2. L’utilisation de la protéine L2, capable d’induire des anticorps cross-neutralisants, est un candidat de choix pour développer un vaccin protégeant contre l'ensemble des papillomavirus HR. Afin d’augmenter la réponse anti-L2, trois systèmes reposant sur l'interaction streptavidine/biotine ont été évalués pour exposer la protéine L2 à de multiples copies à la surface de VLP.Enfin, une stratégie reposant sur l’immunisation avec des PsV, composés des protéines L1 et L2 de l’HPV 58 contenant le gène de la protéine L2 de l’HPV 31, a également été évaluée. Les résultats obtenus indiquent que les PsV58-31L2 représentent la meilleur formulation de la protéine L2 et permet d’induire des anticorps neutralisants les HPV 16, 31,58 et surtout l'HPV 18, phylogénétiquement éloigné des valences vaccinales. / High risk human papillomaviruses (HR HPV) are the etiologic agents of cervical cancer. Current prophylactic HPV vaccines have been shown to protect against natural infection and against the development of high-grade lesions associated with HPV 16 and 18, both responsible of 70% of cervical cancer. However, these vaccines have not the potential to protect against all the thirteen other HR HPV. The aims of my PhD thesis were to evaluate the quadrivalent anti HPV vaccine and second generation vaccine capacity to induce cross-neutralizing antibodies against HR HPV. First, we have investigated the neutralizing antibodies against HPV 58 and HPV 31 after immunization in a population of 65 vaccinated HPV 31 and HPV 58 DNA-negative Colombian women. The results have shown that 33% and 24% of the immunized women exhibited cross neutralizing antibodies against HPV 31 and HPV 58 one month after vaccination, respectively. HPV 58 pseudovirions generated in a cellular system and used in this study exhibit a 10 fold higher capacity to transduce COS-7 cells than those of the HPV 31 PsV and thus represent an interesting candidate for DNA immunization application. The second and third parts of my work were to develop and analyze the immune response induced by second generation vaccine based on L2 protein. In fact, because L2 protein is able to induce cross-neutralizing antibodies, it represents a good alternative in order to develop broad-spectrum HPV vaccine. In order to enhance the anti-L2 immune response, three systems based on the streptavidin/biotin interaction have been evaluated in order to decorate HPV 16 VLPs with multiple L2 protein.Finally, we have produced HPV58 pseudovirions encoding the HPV31 L2 protein. Results obtained indicated that cross-neutralizing antibodies against HPV 16, 31, 58 and a more distant type HPV 18 are only obtained after immunization with pseudovirions encoding the L2 protein.

Human Papillomaviruses (HPVs) are circular double-stranded DNA (dsDNA) viruses that infect human cutaneous and mucosal tissue. Most HPV infections are benign or cause only minor pathologies. However, infection with one of the ~15 high risk types of HPV is associated with a variety of head/neck and anogenital cancers. All told, HPV infection is thought to cause ~5% of all human cancers and cause ~275,000 deaths per year. Despite causing immense morbidity and mortality, many aspects of how HPV virions successfully establish infection in host cells remain poorly characterized. Infection begins with HPV virions binding the cell surface, where they are modified by the host protease furin. The HPV virions are then endocytosed by association with an unknown entry receptor(s). After endocytosis the HPV minor capsid protein L2 acts as a chaperone to ensure that the viral genome (vDNA) traffics from endosomes to the trans-Golgi network (TGN) and eventually the nucleus, where HPV replication occurs. En route to the nucleus, the L2/vDNA complex must translocate across limiting intracellular membranes. The details of these critical processes remain poorly characterized. In this work we investigate the viral and host factors involved in the penetration of host membranes by the HPV L2/vDNA complex. First, we elucidated many of the viral and host factors necessary for furin cleavage of L2. We also demonstrate that furin cleavage mediates the homo-oligomerization and membrane insertion of L2. Finally we demonstrate that complete translocation across the limiting membrane is dependent on host cell entry into mitosis. Overall this work provides novel insight into the molecular mechanisms used by HPV virions to breach host membranes and establish infection.

The aims of this study are twofold: (1) to examine the development of linguistic humor interpretation and comprehension by second language (L2) Spanish learners by using a linguistic humor instrument comprised of comic strips, considering the linguistic properties of Spanish; and (2) to see whether and how reading comprehension ability is reflected in the understanding of four types of linguistic-based humor (i.e. semantic, syntactic, phonological, and morphological). Also discussed are the comprehension strategies utilized by the participants during humor processing. To address these goals, a mixed methods approach was implemented through a linguistic humor multiple-choice questionnaire together with a think-aloud protocol. Results are discussed with reference to Raskin’s (1985) Semantic-Script Switch Theory of Humor (SSTH). The data indicate: (1) comprehension of linguistic-based humor increases with L2 study; (2) L2 learners struggle most with polysemic lexical items; and (3) cognate status and pseudofamiliar words impede comprehension. Considering the analysis of the data, a reassessment of the SSTH and how it applies to L2 humor processing is suggested. Notably, linguistic-based scripts tend to dominate access to other non-linguistic based scripts because L2 learners remain within the linguistic-script frame and are unable to access and/or utilize non-linguistic scripts such as background knowledge. Furthermore, L2 learners contend with error scripts as an additional obstacle, which NS do not experience. The findings suggest that learners should be encouraged and explicitly taught about lexical depth in order to increase their ability to infer meaning from context, thereby increasing their metalinguistic knowledge base. Recommendations are made for the adjustment of the SSTH theory to be more inclusive of L2 learning environments. Finally, suggestions for the L2 classroom include: (1) methods to increase metacognitive awareness; and (2) pedagogical approaches to introduce language-based humor. / text

It is the major purpose of this thesis to propose finite difference techniques of improved accuracy for the numerical solution of ordinary differential equations, and for the numerical evaluation of definite integrals, the former problem being discussed in Chapter II, and the latter in Chapter IV. In Chapter III the stability of the formulae evolved in Chapter II is studied.

In order to investigate the effect of the elimination of GOGAT activity in S. cerevisiae, the pool sizes of ammonia, glutamate and glutamine plus the specific activities of the enzymes involved in ammonia assimilation were determined for two genetically engineered strains (AR2 and AR5) and an haploid wild type ( Sigma 1278b). AR2 and AR5 strains carry the plasmid pCYG4 which directs about 5 fold more NADPH-GDH activity than wild type cells. AR5 strain is a double mutant, which lacks GOGAT activity. The studies were carried out using a microprocessor-controlled fermenter (PCS) which has the following features: 3 Main Boards (Central Processor Board, Memory Board and Analog/Digital - ON/OFF Switch Board). 4 Auxiliary Boards (pH, Oxygen, Temperature and Biomass Interface Boards). A connection block to link the PCS with the video terminal, with sensors from the fermenter, with a control box and with other microcomputer. AR2 and AR5 showed lower values of maximum specific growth rates than the wild type, determined either by batch mode or by washout kinetics. The reduction in the growth rate for AR2 and AR5 can be related to the added metabolic loads due to the plasmid encoded genes. Under carbon limitation there were no remarkable differences between the NADPH-GDH activities of AR2 (GOGAT+) and AR5 (GOGAT-). However, the concentrations of glutamate and glutamine for AR2 were higher (from 20 to 40 %) than those of AR5. The lack of the GOGAT activity also resulted in a decrease in the biomass concentration for AR5 compared to the GOGAT+ strains. Under nitrogen limitation NADPH-GDH activities were higher and intracellular ammonia concentrations lower than under carbon limited conditions. The intracellular concentrations of glutamate and glutamine were higher for the GOGAT+ strain than for the GOGAT- one. Although the biomass level was the same for the three strains, AR5 (GOGAT") cells changed from rounded to ellipsoidal form under nitrogen limited conditions. Oscillations were present in the NADPH-GDH activities of AR2 and AR5 strains growing under carbon and nitrogen limited media. They are probably due to segregational instability of the plasmid pCYG4 in these microorganisms.

Since the 1990s, the number of U.S. students enrolled in university-level Chinese language classes has grown exponentially. Learning Chinese has become increasingly important to those students’ academic studies, professional success, and personal development. However, despite these students’ eagerness to master Chinese, they face an inevitable challenge to their progress: developing reading fluency and comprehension skills in Chinese. A common experience among those students is that learning to read in Chinese is labor-intensive and frustrating, and it takes much longer than the time they would have to spend on learning to read in alphabetic languages such as Spanish, French, and German. In response to this issue, a small but growing body of research has started to investigate the ways American learners view and comprehend Chinese texts. To contribute to this line of research, the present study examined the process of reading Chinese as a second language (L2 Chinese reading). In particular, this study looked closely into the following key questions: (1) What strategies did L2 Chinese readers use when reading a Chinese expository text? (2) What difficulties did they encounter and how did they solve these problems? (3) What factors influenced their reading process? (4) When, how and why did they shift to thinking in their native language, English? To describe these readers’ approaches to text comprehension and also to understand their own perceptions, this study adopted a few qualitative research methods, including think-aloud reports, recall protocols, post-reading interviews, semi-structured interviews and background surveys. Participants of this study were five American students enrolled in intermediate- and advanced-level Chinese language classes at a Midwest U.S. university. Data collected from these participants were analyzed qualitatively through both an intuitive, holistic approach and a structured, systematic approach. A qualitative data analysis software—NVivo 12—was used to facilitate the coding and analysis process. Results of the study show that L2 (Chinese) reading is primarily a language-based, cognitive-constrained, and individualized process that involves multiple interactive factors. Those factors include but are not limited to linguistic, psychological, textual, environmental, and background factors. In addition, regarding the use of the native language in L2 reading, results of the study show that readers’ L2 language proficiency influences the frequency and effectiveness of their use of their native language. The ways of using the native language also differed across readers with different L2 language proficiencies and reading styles. These results have implications for theories of L2 reading in general and theories of L2 Chinese reading in particular. Pedagogical implications and directions for future research are also discussed at the end of the dissertation.

Heeding the call by Firth and Wagner (1997) for a re-analysis of some of the “facts” of modern second language (L2) learning theory and research, the goals of this present study are to determine if: (1) informal conversations between a NS of English (NES) learning Spanish and a NS of Spanish (NSS) learning English reveal insight regarding the natural use and interaction of the first (L1) and the target language (TL); (2) informal L2 conversations in which the L1 is permitted present opportunities for L2 teaching, learning or socialization; and (3) provided that evidence of possible opportunities for L2 teaching, learning or socialization is found, does this indicate a need for permitting both informal talk and the use of the L1 in the L2 learning context. It was hypothesized that in informal conversations, learners would demonstrate intuitive approaches to L2 learning, teaching and socialization, and that observations of these phenomena could help guide research and pedagogy regarding the L2 learning context. It was also hypothesized that informal language exchanges would demonstrate that when left to intuition, participants would provide quality NS input and modified NNS output for their partners as they alternated between L1 and L2 and between the roles of language teacher and language learner. Previous studies have shown that the ability to control the language being used and the topic being discussed allows learners to access knowledge and linguistic structures that enable them to feel more comfortable using the L2 and less anxious about interacting in L2 conversations (Auerbach 1993; Tomlinson 2001; Lantolf and Thorne 2007). The design of this study was intended to address the concept of bi-directional informal discourse in learner/expert learner/expert pairs (i.e., participants who are each learners of their partners’ L1) and the informal exchange of two languages in the L2 learning context. Although the importance of language learning and use in context have been described since the early 20th century in the work of Vygotsky, and the phenomenon of participant orientation and role-switching has also been examined in recent years, there have been relatively few studies that have looked at the nexus of social talk and reciprocal teaching by pairs of learner/experts as this context interacts with the use of the L1 and the L2 in an informal communication event. Data for the study were obtained from audio recordings of four conversations between pairs of native Spanish speakers learning English and native English speakers learning Spanish with the goal of determining what the participants would teach to one other through the use of informal, unstructured conversation using both the L1 & the L2. In addition, all of the participants completed an exit interview questionnaire on their experience with the interaction as well as their general opinions regarding language learning. The data showed that 7 out of 8 participants did teach (intentionally or unintentionally) both linguistic and extra-linguistic information from their L1 to their partners, and that in all pairs a local set of rules regarding the use of the L1was established (including the pair in which no English was used). The pairs modeled an intuitive use of the L1 demonstrating the ability of the L1 both to bridge conversational gaps and to enable teaching and socialization in the L2. The data also show how the participants built a community of practice by setting and changing the language used, requesting explicit feedback or evaluation from their partners, bonding over language learning struggles, as well the linguistic and extra-linguistic information that the participants provided for their partners. The results of the study indicate potential benefits both for the use of the L1 in the L2 learning context, and for allowing learners to teach from their own L1 while learning the L2 in informal conversations. However, the recordings and the exit interviews also show some potential problems for implementation (e.g., the possibility that a conversation may be carried out in just one language). The conclusions present implications and applications for the study, such as the establishment of language exchange programs as a supplement to traditional L2 classes, as well as the limitations of the study and suggestions for further research. / text

Writing has increasingly been emphasised in EFL classrooms in recent years, and Korea is no exception to this trend. The literature indicates that L2 writers experience language problems and attempt to solve them while converting their thoughts into another language. At the moment when learners struggle with a linguistic feature, they become aware of their lack of linguistic knowledge, and try to resolve the problem either by employing their own previously acquired knowledge sources, or by trying to access external knowledge sources. This problem-solving process may occur repeatedly during the L2 writing process. The aims of the current research are threefold: first, it investigates what Korean university learners of English notice while they are writing in L2; second, it attempts to examine what variables are related to and affect learners' noticing during the L2 problem-solving process and; third, the knowledge sources employed by learners when they face language problems are analysed. In order to achieve these aims, 108 English major students were recruited from three high ranked universities in Korea; think-aloud protocols and stimulated-recall interviews comprised the primary means of data collection. All participants were asked to do a writing task in L2 and to verbalise their thoughts while producing written text. Building on the data gathered from the writing task, stimulated recall interviews were carried out in order to identify the sources of knowledge employed to resolve language problems. The results of quantitative data analysis showed that the 108 participants in this study noticed approximately five language problems while writing an L2 text for 20 minutes, and verbally expressed many more lexical episodes than grammatical episodes. Regarding the relations between learner-related variables and noticing during the L2 writing process, previous study abroad experience and L2 proficiency affected learners' noticing. It was also found that L2-based verbal working memory had an effect when learners notice language problems in L2 text production, while L1-based verbal working memory had no effect. Moreover, qualitative data analysis indicated that the participants employed various types of knowledge sources in order to solve lexical or grammatical problems. It was found that both explicit linguistic knowledge sources, such as previously acquired L1-L2 translation word pairs, aspects of word knowledge (i.e., form, meaning, or use), episodic memory or analogy, and implicit knowledge sources, such as intuition, were used during the L2 problem-solving process. Based on these findings, possible implications for L2 writing teaching are discussed, stressing the importance of providing many writing opportunities for students, and suggestions for future research are presented.