Indiana University-Purdue University Indianapolis (IUPUI) / This thesis presents a novel technique and framework for decreasing instrumenta- tion overhead in software systems that utilize dynamic binary instrumentation. First, we introduce a lightweight networking framework combined with an easily extensible BSON implementation as a heavy analysis routine replacement. Secondly, we bind instrumentation and analysis threads to non-overlapping cpu cores--allowing analysis threads to execute faster. Lastly, we utilize a lock-free buffering system to bridge the gap between instrumentation and analysis threads, and minimize the overhead to the instrumentation threads. Using this combination, we managed to write a dynamic binary instrumentation tool (DBI) in Pin using Pin++ that is almost 1100 % faster than its counterpart DBI tool with no buffering, and less than 500% slower than a similar tool with no analysis routine.

No description available.

Unique among the intracellular lipid binding proteins, acyl CoA binding protein (ACBP) exclusively binds long chain fatty acyl CoAs (LCFA-CoAs). To test if ACBP is an essential protein in mammals, the ACBP gene was ablated by homologous recombination in mice. While ACBP heterozygotes appeared phenotypically normal, intercrossing of the heterozygotes did not result in any live homozygous deficient (null) ACBP^(-/-) pups. Heterozygous and wild type embryos were detected at all postimplantation stages, but no homozygous ACBP null embryos were obtained– suggesting that an embryonic lethality occurred at a preimplantation stage of development, or that embryos never formed. While ACBP null embryos were not detected at any blastocyst stage, ACBP null embryos were detected at the morula (8- cell), cleavage (2-cell), and zygote (1-cell) preimplantation stages. Two other LCFACoA binding proteins, sterol carrier protein-2 (SCP-2) and sterol carrier protein-x (SCPx) were significantly upregulated at these stages. These findings demonstrate for the first time that ACBP is an essential protein required for embryonic development and its loss of function may be initially compensated by concomitant upregulation of two other LCFA-CoA binding proteins only at the earliest preimplantation stages. The fact that ACBP is the first known intracellular lipid binding protein whose deletion results in embryonic lethality suggests its vital importance in mammals.

La maladie de Parkinson (MP) est un trouble neurodégénératif caractérisé par une perte progressive de neurones dopaminergiques (DA) de la substance noire pars compacta (SNpc). Différents mécanismes sont associés à la neuropathogénèse de la MP et en particulier le dysfonctionnement de la chaîne respiratoire mitochondriale, le stress oxydatif, l’apoptose et les processus neuro-inflammatoires. L'octadécaneuropeptide (ODN) est un peptide dérivé du diazepam-binding inhibitor (DBI) exprimé par les cellules astrogliales, qui exerce une action neuroprotectrice dans un modèle cellulaire in vitro de la MP. A ce jour, aucune étude in vivo n’a été réalisée, afin de déterminer si les données obtenues sur les modèles cellulaires in vitro peuvent être transposées in vivo. Le projet de cette thèse consiste ainsi à mettre en évidence l’action protectrice de l’ODN sur la survie des neurones DA de la SNpc dans un modèle murin de la MP et à rechercher les conséquences de l’invalidation du gène du précurseur de l’ODN (DBI) sur la vulnérabilité des neurones DA. Les résultats obtenus montrent qu’une seule injection intra-cérébroventriculaire d’une faible quantité d’ODN (10 ng), 1 h après la dernière administration systémique de 1-méthyl-4-phényl-1,2,3,6-tétrahydropyridine (MPTP) prévient significativement la perte des neurones DA dans la substance noire et la dégénérescence de leurs prolongements nerveux vers le striatum comme mesuré par des marquages et des mesures d’expression de la tyrosine hydroxylase. Cet effet neuroprotecteur de l’ODN est accompagné par une réduction du nombre d’astrocytes réactifs, une forte inhibition de l'expression de gènes pro-inflammatoires tels que les interleukines (IL) IL-1β et IL-6, et tumor necrosis factor-α. De plus, l'ODN bloque l'inhibition du gène anti-apoptotique Bcl-2 et la stimulation des gènes pro-apoptotiques Bax et caspase-3, induite par le MPTP dans la SNpc et le striatum. L'ODN réduit également l’accumulation d'espèces réactives de l'oxygène (ROS) et de produits d'oxydation lipidique dans les neurones DA. Par ailleurs, les souris knock-out DBI (DBI-/-) sont plus vulnérables que les animaux sauvages (DBI+/+) vis-à-vis de la neurotoxicité du MPTP. L’absence de production d’ODN endogène, chez les souris DBI-/- parkinsoniennes, augmente les dommages cellulaires induits par le MPTP, la réactivité gliale, les taux de ROS, l’expression de cytokines pro-inflammatoires et l'activité de la caspase-3 dans la région nigro-striée. L’ensemble de ces résultats montre que le gliopeptide ODN exerce un puissant effet neuroprotecteur contre la dégénérescence des neurones DA de la SNpc induite par le MPTP, chez la souris. Cette action protectrice met en jeu des mécanismes impliquant l’inhibition des processus neuro-inflammatoires, oxydatifs et apoptotiques. D’autre part, la déficience en ODN potentialise les effets délétères du MPTP, suggérant que ce peptide joue un rôle clé lors de la réponse à un stress cellulaire. / Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of loss of dopaminergic (DA) neurons within the substantia nigra pars compacta (SNpc). Different mechanisms are associated with the neuropathogenesis of PD including dysfunction of the mitochondrial respiratory chain, oxidative stress, apoptosis and neuroinflammatory processes. Octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. Nevertheless, its protective action in vivo has never been investigated. Therefore, the aim of the project of this thesis was to investigate whether intracerebroventricular (i.c.v) injection of ODN could prevent DA neuron degeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and to explore the vulnerability of ODN precursor knockout (DBI KO) mice to MPTP-induced neurotoxicity. The results show that a single i.c.v injection of 10 ng/μl ODN, 1 h after the last systemic administration of MPTP, prevents the reduction of the number of tyrosine hydroxylase (TH)-positive cell bodies and fibers in the SNpc and striatum, respectively. Immunofluorescence imaging, Western blot analysis and Q-PCR studies revealed that ODN totally abolished MPTP-induced decrease of TH positive cells, mRNA expression and protein levels. This neuroprotective effect of ODN is accompanied by a reduction in the number of reactive astrocytes, an inhibition of the expression of pro-inflammatory genes such as interleukins (IL) IL-1β and IL-6, and a decrease of tumor necrosis factor -α. In addition, ODN blocks the inhibition of the anti-apoptotic Bcl-2 gene and the stimulation of Bax and caspase-3 expression induced by MPTP in the SNpc and striatum. ODN also reduces the accumulation of reactive oxygen species (ROS) and lipid oxidation products in DA neurons. Furthermore, DBI-/- mice exhibited more vulnerability to MPTP than wild-type animals (DBI+/+). Thus, ODN KO mice are more sensitive to MPTP-induced inflammatory and oxidative brain damages, suggesting that the endogenous OD may also be neuroprotective. These results indicate that, based on its anti-oxidative, anti-inflammatory and anti-apoptotic effect, the gliopeptide ODN could lead to the development of effective therapeutic agents for the treatment of cerebral injuries involving oxidative neurodegeneration.

South Africa was invited to join the Brazil, Russia, India and China (BRIC) group at the end of 2010, mainly because South Africa is viewed as the ‘gateway’ into Africa, and South Africa is also considered to be the link between BRIC and the Southern African Development Community (SADC). It is expected that the BRIC countries will increase their foreign direct investment (FDI) to South Africa. This inflow of BRIC FDI may lead to the advantages of boosting SADC exports, which is important as it may lead to the SADC countries experiencing expanded market opportunities, and exports have for a long time been viewed as an engine of economic growth. It has been further indicated that it is evident that relatively few studies have been conducted on the relationship between FDI and exports within the African context and that this relationship is not well understood. In light of these shortcomings in the literature, the first aim of this study was to attempt to contribute to the literature on FDI in SADC by investigating the relationship between BRIC FDI inflows on SADC exports. From the assessment of recent studies conducted on the relationship between FDI and exports in developed, developing and African countries a number of conclusions have been made. The first was that the majority of the studies conducted between 2000 and 2011 by various authors used causality tests and regression models to determine the relationships between FDI and exports. It also seemed that bi-directional causality is most often found, thereby indicating that FDI has a positive influence on exports and exports also have a positive influence on FDI. The secondary research aim, to determine the specific relationship between the BRIC’s FDI on SADC exports to BRIC and the world, was analysed by means of a descriptive and empirical study (correlation test, regression model, Granger causality test and panel data causality testing method), and the results indicated that, from 2003 to 2011, there was a strong positive correlation between BRIC FDI inflows to SADC and SADC exports to BRIC (59 per cent) and the world (96 per cent). The regression analysis showed that 53 per cent of the variance in the SADC exports to the BRIC is explained by BRIC FDI, while 99 per cent of the variance in the SADC exports to the world is explained by BRIC FDI. Finally the Granger causality test results indicated that BRIC FDI inflows contributed to higher exports from SADC, specifically SADC exports to the world. This was however not the case for SADC exports to BRIC. The results further suggest that there is a possible cointegration between BRIC FDI and the SADC exports to the world, reflecting, among other things, that the simultaneous movement of BRIC FDI inflows with SADC exports to the world may be mainly due to exogenous factors rather than a direct causal relationship. The BRIC FDI inflows on the SADC exports to the world being significant is a motivation for the SADC group to further motivate integration, co-operation and participation within BRIC, as this may possibly lead to further inward FDI flows, which may further promote exports to the world. Future studies would include determining the market forces that contribute to the simultaneous movement of BRIC FDI inflows into SADC, with the SADC exports to the world. / MCom (International Trade), North-West University, Potchefstroom Campus, 2013

South Africa was invited to join the Brazil, Russia, India and China (BRIC) group at the end of 2010, mainly because South Africa is viewed as the ‘gateway’ into Africa, and South Africa is also considered to be the link between BRIC and the Southern African Development Community (SADC). It is expected that the BRIC countries will increase their foreign direct investment (FDI) to South Africa. This inflow of BRIC FDI may lead to the advantages of boosting SADC exports, which is important as it may lead to the SADC countries experiencing expanded market opportunities, and exports have for a long time been viewed as an engine of economic growth. It has been further indicated that it is evident that relatively few studies have been conducted on the relationship between FDI and exports within the African context and that this relationship is not well understood. In light of these shortcomings in the literature, the first aim of this study was to attempt to contribute to the literature on FDI in SADC by investigating the relationship between BRIC FDI inflows on SADC exports. From the assessment of recent studies conducted on the relationship between FDI and exports in developed, developing and African countries a number of conclusions have been made. The first was that the majority of the studies conducted between 2000 and 2011 by various authors used causality tests and regression models to determine the relationships between FDI and exports. It also seemed that bi-directional causality is most often found, thereby indicating that FDI has a positive influence on exports and exports also have a positive influence on FDI. The secondary research aim, to determine the specific relationship between the BRIC’s FDI on SADC exports to BRIC and the world, was analysed by means of a descriptive and empirical study (correlation test, regression model, Granger causality test and panel data causality testing method), and the results indicated that, from 2003 to 2011, there was a strong positive correlation between BRIC FDI inflows to SADC and SADC exports to BRIC (59 per cent) and the world (96 per cent). The regression analysis showed that 53 per cent of the variance in the SADC exports to the BRIC is explained by BRIC FDI, while 99 per cent of the variance in the SADC exports to the world is explained by BRIC FDI. Finally the Granger causality test results indicated that BRIC FDI inflows contributed to higher exports from SADC, specifically SADC exports to the world. This was however not the case for SADC exports to BRIC. The results further suggest that there is a possible cointegration between BRIC FDI and the SADC exports to the world, reflecting, among other things, that the simultaneous movement of BRIC FDI inflows with SADC exports to the world may be mainly due to exogenous factors rather than a direct causal relationship. The BRIC FDI inflows on the SADC exports to the world being significant is a motivation for the SADC group to further motivate integration, co-operation and participation within BRIC, as this may possibly lead to further inward FDI flows, which may further promote exports to the world. Future studies would include determining the market forces that contribute to the simultaneous movement of BRIC FDI inflows into SADC, with the SADC exports to the world. / MCom (International Trade), North-West University, Potchefstroom Campus, 2013

The work is centered on the study of dimensionally reduced vector effective field theories from the point of view of soft scalar limits using the spinor-helicity formalism. The Dirac-Born-Infeld model is singled out by its enhanced soft limit at the level of four and six-point amplitudes. In the process, the spinor-helicity formalism is outlined and its use illustrated on explicit examples. The remainder of the work is focused on the corresponding questions in six dimensions. The rel- evant version of spinor-helicity formalism is presented, followed by a discussion of little group invariants and of the (im)possibility of their use on characteriza- tion of theories. Lastly, attempts at formalizing the process of taking the soft limit are made, with inspiration from the four-dimensional case. 1

Los receptores GABA_A son canales iónicos activados por ligandos y funcionan como los principales mediadores de la inhibición en el sistema nervioso central de mamíferos. Están formados por cinco subunidades formando un poro central conductor de iones. Cada combinación de subunidades presenta una función y localización determinada, de las cuales el subtipo α1ß2γ2 es el más abundante en el ser humano. Los receptores GABA_A intervienen en una miríada de procesos neurológicos y su desregulación genera las denominadas canalopatías. Por lo cual, el estudio de estos sistemas es indispensable para el desarrollo de fármacos y de tratamientos para mejorar la calidad de vida. En este trabajo de tesis se propone el estudio in silico del receptor GABA_A α1ß2γ2 mediante el empleo de técnicas de bioinformática y biofísica computacional, que incluyen simulaciones de docking molecular, dinámica molecular y técnicas de muestreo avanzado. Se desarrolló un modelo por homología del receptor empleando el receptor GABA_A homopent mero de subunidades ß3. El modelo fue validado a través de un cuidadoso análisis de su estereoquímica y su estabilidad mediante simulaciones de dinámica molecular. A continuación, se realizó un exhaustivo análisis de la unión de compuestos a dos sitios de unión en el dominio extracelular del modelo: el sitio ortostérico (donde se unen los ligandos que actúan directamente sobre la activación del canal) y el sitio de unión de gran afinidad de las benzodiazepinas (moduladores alostéricos). Los modos de unión encontrados fueron contrastados con información experimental disponible y se halló muy buena concordancia. El trabajo finalizó con el primer estudio computacional sobre la interacción putativa entre este receptor y la proteína DBI y fragmentos peptídicos derivados de su digestión. Este análisis permitió elaborar, por primera vez, una hipótesis respecto a los residuos involucrados en la interacción. / GABA_A receptors are pentameric ligand-gated ion channels which act as the main mediators of inhibitory signalling in the central nervous system of mammals. They are formed by five subunits arranged around a central ion-conducting pore. Each combination of subunits has a specific function and localization, the α1ß2γ2 subtype being the most abundant in homo sapiens. These receptors intervene in a myriad of neurological processes and their disregulation cause several channelopathies. Although they are very complex systems, their study is fundamental for the development of new drugs and therapies aimed at improving life quality. In this thesis we performed an in silico study of the α1ß2γ2 GABA_A receptor through the use of bioinformatics and computational biophysics tools, which include molecular docking, molecular dynamics and enhanced sampling techniques. A homology model was developed using the structure of the GABAA_A ß3 homopentamer. The model was validated through a thorough analysis of its stereochemistry and its stability was evaluated from molecular dynamics simulations. Moreover, an exhaustive evaluation of the binding modes of ligands to two extracellular sites was performed: the orthosteric site (ligands which act directly on the activation of the channel) and the high affinity binding site for benzodiazepines (allosteric modulators). The comparison of the binding modes to available experimental information showed great agreement. Finally, a computational study was carried out for the first time regarding the putative interaction of this receptor with DBI and its peptide fragments. This study allowed the formulation of the first hypotheses regarding the aminoacids involved in the interaction.

Snow algae as typical extremophiles are good model organisms for study of adaptation for life on the boundary of physiological possibilities. So far, it is not clear, how these microorganisms ensure on the molecular level the optimization of photosynthetic processes in conditions around 0 řC, often with very high light intensity. The aim of this work was to find out light and temperature growth optima of two less studied strains and to assess the composition of fatty acids in selected psychrophilic and psychrotrophic strains from the genera Chloromonas and Chlamydomonas (Chlamydomonadales, Chlorophyta) from culture collections UTEX and CCCryo and collections in Europe including the Czech Republic and Slovakia. Using crossed gradients method, this thesis describes optimal temperature and light conditions of two strains of snow algae isolated from sites in the Krkonoše Mountains that are characterized by different ecological conditions. The strain Chloromonas reticulata Luční originates from alpine zone and according to its growth characteristics, it can be classified as psychrotrophic alga requiring high light. The second tested strain was Chloromonas pichinchae Meandry from forest environment, which is also characterized as psychrotrophic, In contrast to previous strain, it grows in a wide range of...

Educational Psychology / Built from a diverse background of theatre-based education and social change theories, drama-based instruction (DBI) employs active, kinesthetic learning strategies to engage students in classroom activities. Much of DBI is grounded in scaffolding students through a Describe, Analyze, and Relate (DAR) thinking process. DAR requires students to consider information in a systematic way, leading them through the steps of Bloom’s Taxonomy and moving from lower-order to higher-order thinking skills. Examining information at this deeper level is a process similar to the automatic thought-stopping mechanism of Cognitive-Behavioral Therapy (CBT). As in CBT, rather than making hasty assumptions, students are guided through steps that allow them to analyze details and to examine stimuli thoroughly. Yet the context of DBI is different from many CBT therapeutic settings because DBI is situated in a classroom environment. DAR is delivered as a whole-class intervention with peer interaction occurring throughout the thinking and questioning process. Social perspective-taking involves one individual’s efforts to discern the thoughts and feelings of another individual, a skill that has been linked to more effective problem solving. When teachers offer structured exposure to thought-stopping and perspective-taking processes, students gain practice with social perspective-taking and problem-solving skills. The current study proposed a multiple baseline, single-case design to explore how practice using the Describe, Analyze, Relate (DAR) questioning technique affects students’ capacity to engage in social perspective-taking and social problem-solving. The school in this study participated in a year-long, campus-wide initiative to train teachers in how to use DAR across subjects and grade levels. Two fourth grade teachers, one fifth grade teacher, and one visual arts teacher were identified as demonstrating proficiency in the DAR technique. In each of the three core teachers’ classes, a letter was sent home explaining the project and requesting opt-in from interested parents. From those who responded, students with special education placements were removed, then two students were randomly selected per class. The researcher met individually with the selected participants to conduct repeated measures of the Interpersonal Negotiating Strategies Interview for baseline, intervention, and follow-up phases of the study over the course of the 2012-2013 school year. Additionally, participants’ teachers were asked to complete the Social Skills subscale of the Behavior Assessment System for Children for each phase of data collection. Post-intervention interviews were conducted with the teachers to assess for their perceptions of the DAR strategy and DBI-based pedagogy in general. Visual analysis was used to assess the effectiveness of the treatment on student social perspective-taking and problem-solving. Overall, the quantitative results of the current study did not conclusively link DAR with social perspective-taking and problem-solving. However, the qualitative data from teacher interviews yielded positive feedback related to the utility of DAR questioning on improving higher-order thinking in their students. Further research is necessary to clarify and deepen understanding of this effect. / text