Invasive species and habitat degradation in Iberian streams: an analysis of their role in freshwater fish diversity loss

Mediterranean endemic freshwater fish are among the most threatened biota in the world. Distinguishing the role of different extinction drivers and their potential interactions is crucial for achieving conservation goals. While some authors argue that invasive species are a main driver of native species declines, others see their proliferation as a co-occurring process to biodiversity loss driven by habitat degradation. It is difficult to discern between the two potential causes given that few invaded ecosystems are free from habitat degradation, and that both factors may interact in different ways. Here we analyze the relative importance of habitat degradation and invasive species in the decline of native fish assemblages in the Guadiana River basin (southwestern Iberian Peninsula) using an information theoretic approach to evaluate interaction pathways between invasive species and habitat degradation (structural equation modeling, SEM). We also tested the possible changes in the functional relationships between invasive and native species, measured as the per capita effect of invasive species, using ANCOVA. We found that the abundance of invasive species was the best single predictor of natives’ decline and had the highest Akaike weight among the set of predictor variables examined. Habitat degradation neither played an active role nor influenced the per capita effect of invasive species on natives. Our analyses indicated that downstream reaches and areas close to reservoirs had the most invaded fish assemblages, independently of their habitat degradation status. The proliferation of invasive species poses a strong threat to the persistence of native assemblages in highly fluctuating environments. Therefore, conservation efforts to reduce native freshwater fish diversity loss in Mediterranean rivers should focus on mitigating the effect of invasive species and preventing future invasions

Modeling of water/steam circulation in Circulating Fluidized Bed boiler

A distinctive design feature of steam boiler with natural circulation is the presence of the steam drum which plays a role of the separator of vapor from the flow of water-and-steam mixture coming into steam drum from the furnace tubes. Steam drum with unheated downcomer tubes, deducing from it, and riser (screen/furnace tubes) inside the furnace is a closed circulation loop in which movement of water (downcomer tubes) and water-and-steam mixture (riser tubes) is organized. The movement of the working fluid is appears due to occurrence of the natural pressure, determined by the difference in hydrostatic pressure and the mass of water and water-and-steam mixtures in downcomer and riser tubes and called the driving pressure of the natural circulation:

Role of oxidation-reduction cycle of iron in direct leaching of zinc concentrate

Direct leaching is an alternative to conventional roast-leach-electrowin (RLE) zinc production method. The basic reaction of direct leach method is the oxidation of sphalerite concentrate in acidic liquid by ferric iron. The reaction mechanism and kinetics, mass transfer and current modifications of zinc concentrate direct leaching process are considered. Particular attention is paid to the oxidation-reduction cycle of iron and its role in direct leaching of zinc concentrate, since it can be one of the limiting factors of the leaching process under certain conditions. The oxidation-reduction cycle of iron was experimentally studied with goal of gaining new knowledge for developing the direct leaching of zinc concentrate. In order to obtain this aim, ferrous iron oxidation experiments were carried out. Affect of such parameters as temperature, pressure, sulfuric acid concentration, ferrous iron and copper concentrations was studied. Based on the experimental results, mathematical model of the ferrous iron oxidation rate was developed. According to results obtained during the study, the reaction rate orders for ferrous iron concentration, oxygen concentration and copper concentration are 0.777, 0.652 and 0.0951 respectively. Values predicted by model were in good concordance with the experimental results. The reliability of estimated parameters was evaluated by MCMC analysis which showed good parameters reliability.

Modeling of water/steam circulation in Circulating Fluidized Bed boiler

A distinctive design feature of steam boiler with natural circulation is the presence of the steam drum which plays a role of the separator of vapor from the flow of water-and-steam mixture coming into steam drum from the furnace tubes. Steam drum with unheated downcomer tubes, deducing from it, and riser (screen/furnace tubes) inside the furnace is a closed circulation loop in which movement of water (downcomer tubes) and water-and-steam mixture (riser tubes) is organized. The movement of the working fluid is appears due to occurrence of the natural pressure, determined by the difference in hydrostatic pressure and the mass of water and water-and-steam mixtures in downcomer and riser tubes and called the driving pressure of the natural circulation: S drive = H steam (ρ down + ρ mix) g where: ρ down - density of water in downcomer tubes; ρ mix - density of water in riser tubes; H steam - height of steam content section; g - acceleration of gravity. In steam boilers with natural circulation the circulation rate is usually between 10 and 30. Thus, consumption of water in the circulation circuit “circulation rate times” more than steam output of the boiler. There are two aspects of the design of natural water circulation loops. One is to ensure a sufficient mass flux of circulating water to avoid burnout of evaporator tubes. The other is to avoid tube wall temperature fluctuation and tube vibration due to oscillation of circulation velocity. The design criteria are therefore reduced, in principle, to those of critical heat flux, critical flow rate for burnout, and flow instability. In practical design, however, the circulation velocity and the void fraction at the evaporator tube outlet are used as the design criteria (Seikan I., et. al., 1999). This study has been made with assumption that the heat flux in the furnace of the boiler even all the time. The target of the study was to define the circulation rate of the boiler, thus average heat flux do not change it. I would like to acknowledge professionals from “Foster Wheeler” company for good and comfortable cooperation.

First principles modeling of metallic alloys and alloy surfaces

By alloying metals with other materials, one can modify the metal’s characteristics or compose an alloy which has certain desired characteristics that no pure metal has. The field is vast and complex, and phenomena that govern the behaviour of alloys are numerous. Theories cannot penetrate such complexity, and the scope of experiments is also limited. This is why the relatively new field of ab initio computational methods has much to give to this field. With these methods, one can extend the understanding given by theories, predict how some systems might behave, and be able to obtain information that is not there to see in physical experiments. This thesis pursues to contribute to the collective knowledge of this field in the light of two cases. The first part examines the oxidation of Ag/Cu, namely, the adsorption dynamics and oxygen induced segregation of the surface. Our results demonstrate that the presence of Ag on the Cu(100) surface layer strongly inhibits dissociative adsorption. Our results also confirmed that surface reconstruction does happen, as experiments predicted. Our studies indicate that 0.25 ML of oxygen is enough for Ag to diffuse towards the bulk, under the copper oxide layer. The other part elucidates the complex interplay of various energy and entropy contributions to the phase stability of paramagnetic duplex steel alloys. We were able to produce a phase stability map from first principles, and it agrees with experiments rather well. Our results also show that entropy contributions play a very important role on defining the phase stability. This is, to the author’s knowledge, the first ab initio study upon this subject.

Application of Computational Fluid Dynamics in Modeling Blood Flow in Human Thoracic Aorta

The aim of this study was to simulate blood flow in thoracic human aorta and understand the role of flow dynamics in the initialization and localization of atherosclerotic plaque in human thoracic aorta. The blood flow dynamics in idealized and realistic models of human thoracic aorta were numerically simulated in three idealized and two realistic thoracic aorta models. The idealized models of thoracic aorta were reconstructed with measurements available from literature, and the realistic models of thoracic aorta were constructed by image processing Computed Tomographic (CT) images. The CT images were made available by South Karelia Central Hospital in Lappeenranta. The reconstruction of thoracic aorta consisted of operations, such as contrast adjustment, image segmentations, and 3D surface rendering. Additional design operations were performed to make the aorta model compatible for the numerical method based computer code. The image processing and design operations were performed with specialized medical image processing software. Pulsatile pressure and velocity boundary conditions were deployed as inlet boundary conditions. The blood flow was assumed homogeneous and incompressible. The blood was assumed to be a Newtonian fluid. The simulations with idealized models of thoracic aorta were carried out with Finite Element Method based computer code, while the simulations with realistic models of thoracic aorta were carried out with Finite Volume Method based computer code. Simulations were carried out for four cardiac cycles. The distribution of flow, pressure and Wall Shear Stress (WSS) observed during the fourth cardiac cycle were extensively analyzed. The aim of carrying out the simulations with idealized model was to get an estimate of flow dynamics in a realistic aorta model. The motive behind the choice of three aorta models with distinct features was to understand the dependence of flow dynamics on aorta anatomy. Highly disturbed and nonuniform distribution of velocity and WSS was observed in aortic arch, near brachiocephalic, left common artery, and left subclavian artery. On the other hand, the WSS profiles at the roots of branches show significant differences with geometry variation of aorta and branches. The comparison of instantaneous WSS profiles revealed that the model with straight branching arteries had relatively lower WSS compared to that in the aorta model with curved branches. In addition to this, significant differences were observed in the spatial and temporal profiles of WSS, flow, and pressure. The study with idealized model was extended to study blood flow in thoracic aorta under the effects of hypertension and hypotension. One of the idealized aorta models was modified along with the boundary conditions to mimic the thoracic aorta under the effects of hypertension and hypotension. The results of simulations with realistic models extracted from CT scans demonstrated more realistic flow dynamics than that in the idealized models. During systole, the velocity in ascending aorta was skewed towards the outer wall of aortic arch. The flow develops secondary flow patterns as it moves downstream towards aortic arch. Unlike idealized models, the distribution of flow was nonplanar and heavily guided by the artery anatomy. Flow cavitation was observed in the aorta model which was imaged giving longer branches. This could not be properly observed in the model with imaging containing a shorter length for aortic branches. The flow circulation was also observed in the inner wall of the aortic arch. However, during the diastole, the flow profiles were almost flat and regular due the acceleration of flow at the inlet. The flow profiles were weakly turbulent during the flow reversal. The complex flow patterns caused a non-uniform distribution of WSS. High WSS was distributed at the junction of branches and aortic arch. Low WSS was distributed at the proximal part of the junction, while intermedium WSS was distributed in the distal part of the junction. The pulsatile nature of the inflow caused oscillating WSS at the branch entry region and inner curvature of aortic arch. Based on the WSS distribution in the realistic model, one of the aorta models was altered to induce artificial atherosclerotic plaque at the branch entry region and inner curvature of aortic arch. Atherosclerotic plaque causing 50% blockage of lumen was introduced in brachiocephalic artery, common carotid artery, left subclavian artery, and aortic arch. The aim of this part of the study was first to study the effect of stenosis on flow and WSS distribution, understand the effect of shape of atherosclerotic plaque on flow and WSS distribution, and finally to investigate the effect of lumen blockage severity on flow and WSS distributions. The results revealed that the distribution of WSS is significantly affected by plaque with mere 50% stenosis. The asymmetric shape of stenosis causes higher WSS in branching arteries than in the cases with symmetric plaque. The flow dynamics within thoracic aorta models has been extensively studied and reported here. The effects of pressure and arterial anatomy on the flow dynamic were investigated. The distribution of complex flow and WSS is correlated with the localization of atherosclerosis. With the available results we can conclude that the thoracic aorta, with complex anatomy is the most vulnerable artery for the localization and development of atherosclerosis. The flow dynamics and arterial anatomy play a role in the localization of atherosclerosis. The patient specific image based models can be used to diagnose the locations in the aorta vulnerable to the development of arterial diseases such as atherosclerosis.

From network pictures to network insight in solution business – the role of internal communication

Operating in business-to-business markets requires an in-depth understanding on business networks. Actions and reactions made to compete in markets are fundamentally based on managers‘ subjective perceptions of the network. However, an amalgamation of these individual perceptions, termed a network picture, to a common company level shared understanding on that network, known as network insight, is found to be a substantial challenge for companies. A company‘s capability to enhance common network insight is even argued to lead competitive advantage. Especially companies with value creating logics that require wide comprehension of and collaborating in networks, such as solution business, are necessitated to develop advanced network insight. According to the extant literature, dispersed pieces of atomized network pictures can be unified to a common network insight through a process of amalgamation that comprises barriers/drivers of multilateral exchange, manifold rationality, and recursive time. However, the extant body of literature appears to lack an understanding on the role of internal communication in the development of network insight. Nonetheless, the extant understanding on the amalgamation process indicates that internal communication plays a substantial role in the development of company level network insight. The purpose of the present thesis is to enhance understanding on internal communication in the amalgamation of network pictures to develop network insight in the solution business setting, which was chosen to represent business-to-business value creating logic that emphasizes the capability to understand and utilize networks. Thus, in solution business the role of succeeding in the amalgamation process is expected to emphasize. The study combines qualitative and quantitative research by means of various analytical methods including multiple case analysis, simulation, and social network analysis. Approaching the nascent research topic with differing perspectives and means provides a broader insight on the phenomenon. The study provides empirical evidence from Finnish business-to-business companies which operate globally. The empirical data comprise interviews (n=28) with managers of three case companies. In addition the data includes a questionnaire (n=23) collected mainly for the purpose of social network analysis. In addition, the thesis includes a simulation study more specifically achieved by means of agent based modeling. The findings of the thesis shed light on the role of internal communication in the amalgamation process, contributing to the emergent discussion of network insights and thus to the industrial marketing research. In addition, the thesis increases understanding on internal communication in the change process to solution business, a supplier‘s internal communication in its matrix organization structure during a project sales process, key barriers and drivers that influence internal communication in project sales networks, perceived power within industrial project sales, and the revisioning of network pictures. According to the findings, internal communication is found to play a substantial role in the amalgamation process. First, it is suggested that internal communication is a base of multilateral exchange. Second, it is suggested that internal communication intensifies and maintains manifold rationality. Third, internal communication is needed to explicate the usually differing time perspectives of others and thus it is suggested that internal communication has role as the explicator of recursive time. Furthermore, the role of an efficient amalgamation process is found to be emphasized in solutions business as it requires a more advanced network insight for cross-functional collaboration. Finally, the thesis offers several managerial implications for industrial suppliers to enhance the amalgamation process when operating in solution business.

Modeling of residual stresses and distortion due to welding in fillet welds

Welding has a growing role in modern world manufacturing. Welding joints are extensively used from pipes to aerospace industries. Prediction of welding residual stresses and distortions is necessary for accurate evaluation of fillet welds in relation to design and safety conditions. Residual stresses may be beneficial or detrimental, depending whether they are tensile or compressive and the loading. They directly affect the fatigue life of the weld by impacting crack growth rate. Beside theoretical background of residual stresses this study calculates residual stresses and deformations due to localized heating by welding process and subsequent rapid cooling in fillet welds. Validated methods are required for this purpose due to complexity of process, localized heating, temperature dependence of material properties and heat source. In this research both empirical and simulation methods were used for the analysis of welded joints. Finite element simulation has become a popular tool of prediction of welding residual stresses and distortion. Three different cases with and without preload have been modeled during this study. Thermal heat load set is used by calculating heat flux from the given heat input energy. First the linear and then nonlinear material behavior model is modeled for calculation of residual stresses. Experimental work is done to calculate the stresses empirically. The results from both the methods are compared to check their reliability. Residual stresses can have a significant effect on fatigue performance of the welded joints made of high strength steel. Both initial residual stress state and subsequent residual stress relaxation need to be considered for accurate description of fatigue behavior. Tensile residual stresses are detrimental and will reduce the fatigue life and compressive residual stresses will increase it. The residual stresses follow the yield strength of base or filler material and the components made of high strength steel are typically thin, where the role of distortion is emphasizing.

Computational modeling of stented coronary arteries

The application of computational fluid dynamics (CFD) and finite element analysis (FEA) has been growing rapidly in the various fields of science and technology. One of the areas of interest is in biomedical engineering. The altered hemodynamics inside the blood vessels plays a key role in the development of the arterial disease called atherosclerosis, which is the major cause of human death worldwide. Atherosclerosis is often treated with the stenting procedure to restore the normal blood flow. A stent is a tubular, flexible structure, usually made of metals, which is driven and expanded in the blocked arteries. Despite the success rate of the stenting procedure, it is often associated with the restenosis (re-narrowing of the artery) process. The presence of non-biological device in the artery causes inflammation or re-growth of atherosclerotic lesions in the treated vessels. Several factors including the design of stents, type of stent expansion, expansion pressure, morphology and composition of vessel wall influence the restenosis process. Therefore, the role of computational studies is crucial in the investigation and optimisation of the factors that influence post-stenting complications. This thesis focuses on the stent-vessel wall interactions followed by the blood flow in the post-stenting stage of stenosed human coronary artery. Hemodynamic and mechanical stresses were analysed in three separate stent-plaque-artery models. Plaque was modeled as a multi-layer (fibrous cap (FC), necrotic core (NC), and fibrosis (F)) and the arterial wall as a single layer domain. CFD/FEA simulations were performed using commercial software packages in several models mimicking the various stages and morphologies of atherosclerosis. The tissue prolapse (TP) of stented vessel wall, the distribution of von Mises stress (VMS) inside various layers of vessel wall, and the wall shear stress (WSS) along the luminal surface of the deformed vessel wall were measured and evaluated. The results revealed the role of the stenosis size, thickness of each layer of atherosclerotic wall, thickness of stent strut, pressure applied for stenosis expansion, and the flow condition in the distribution of stresses. The thicknesses of FC, and NC and the total thickness of plaque are critical in controlling the stresses inside the tissue. A small change in morphology of artery wall can significantly affect the distribution of stresses. In particular, FC is the most sensitive layer to TP and stresses, which could determine plaque’s vulnerability to rupture. The WSS is highly influenced by the deflection of artery, which in turn is dependent on the structural composition of arterial wall layers. Together with the stenosis size, their roles could play a decisive role in controlling the low values of WSS (<0.5 Pa) prone to restenosis. Moreover, the time dependent flow altered the percentage of luminal area with WSS values less than 0.5 Pa at different time instants. The non- Newtonian viscosity model of the blood properties significantly affects the prediction of WSS magnitude. The outcomes of this investigation will help to better understand the roles of the individual layers of atherosclerotic vessels and their risk to provoke restenosis at the post-stenting stage. As a consequence, the implementation of such an approach to assess the post-stented stresses will assist the engineers and clinicians in optimizing the stenting techniques to minimize the occurrence of restenosis.

Mathematical modeling and optimal control of malaria

Malaria continues to infect millions and kill hundreds of thousands of people worldwide each year, despite over a century of research and attempts to control and eliminate this infectious disease. Challenges such as the development and spread of drug resistant malaria parasites, insecticide resistance to mosquitoes, climate change, the presence of individuals with subpatent malaria infections which normally are asymptomatic and behavioral plasticity in the mosquito hinder the prospects of malaria control and elimination. In this thesis, mathematical models of malaria transmission and control that address the role of drug resistance, immunity, iron supplementation and anemia, immigration and visitation, and the presence of asymptomatic carriers in malaria transmission are developed. A within-host mathematical model of severe Plasmodium falciparum malaria is also developed. First, a deterministic mathematical model for transmission of antimalarial drug resistance parasites with superinfection is developed and analyzed. The possibility of increase in the risk of superinfection due to iron supplementation and fortification in malaria endemic areas is discussed. The model results calls upon stakeholders to weigh the pros and cons of iron supplementation to individuals living in malaria endemic regions. Second, a deterministic model of transmission of drug resistant malaria parasites, including the inflow of infective immigrants, is presented and analyzed. The optimal control theory is applied to this model to study the impact of various malaria and vector control strategies, such as screening of immigrants, treatment of drug-sensitive infections, treatment of drug-resistant infections, and the use of insecticide-treated bed nets and indoor spraying of mosquitoes. The results of the model emphasize the importance of using a combination of all four controls tools for effective malaria intervention. Next, a two-age-class mathematical model for malaria transmission with asymptomatic carriers is developed and analyzed. In development of this model, four possible control measures are analyzed: the use of long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic, and screening and treatment of asymptomatic individuals. The numerical results show that a disease-free equilibrium can be attained if all four control measures are used. A common pitfall for most epidemiological models is the absence of real data; model-based conclusions have to be drawn based on uncertain parameter values. In this thesis, an approach to study the robustness of optimal control solutions under such parameter uncertainty is presented. Numerical analysis of the optimal control problem in the presence of parameter uncertainty demonstrate the robustness of the optimal control approach that: when a comprehensive control strategy is used the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the design of cost-effective strategies for disease control with multiple interventions, even under considerable uncertainty of model parameters. Finally, a separate work modeling the within-host Plasmodium falciparum infection in humans is presented. The developed model allows re-infection of already-infected red blood cells. The model hypothesizes that in severe malaria due to parasite quest for survival and rapid multiplication, the Plasmodium falciparum can be absorbed in the already-infected red blood cells which accelerates the rupture rate and consequently cause anemia. Analysis of the model and parameter identifiability using Markov chain Monte Carlo methods is presented.

A comparative study of protoheme and heme d catalases : role of the heme and the heme pocket in catalysis and ligand binding

Catalase dismutes H20 2 to O2 and H20. In successive twoelectron reactions H20 2 induces both oxidation and reduction at the heme group. In the first step the protoheme prosthetic group of beef liver catalase forms compound I, in which the heme has been oxidized from Fe3+ to Fe4+=0 and a porphyrin radical has been created. Compound II is formed by the oneelectron reduction of comp I. It retains Fe4+=0 but lacks the porphyrin radical and is catalytically inert. Molecular structures are available for Escherichia coli Hydroperoxidase II, Micrococcus Iysodeiktus, Penicillium vitale and beef liver enzymes, which contain different hemes and heme pockets. In the present work, the pockets and substrate access channels of protoheme (beef liver & Micrococcus) and heme d (HPII of E. coli and Penicillium) catalases have been analysed using Quanta™ and CharmMTM molecular modeling packages on the Silicon Graphics Iris Indigo 2 computer. Experimental studies have been carried out with two catalases, HPII (and its mutants) and beef liver. Fluoride and formate' are inhibitors of both enzymes, and their binding is modulated by the heme and by distal residues N201 & H128. Both HPII and beef liver enzymes form compound I with H202 or peracetate. The reduction of beef liver enzyme compound I to II and the decay of compound II are accelerated by fluoride. The decay of compound II is also accelerated by formate, and this reagent acts as a 2-electron donor towards compound I of both enzymes. It is concluded that heme d enzymes (Penicillium and HPII of E. coli) are formed by autocatalytic transformation of protoheme in a modified pocket which contains a characteristic serine residue as well as a partially occluded heme channel. They are less active than protoheme enzymes but also do not form the inactive compound II species. Binding of peroxide as well as fluoride and formate is prevented by mutation of H128 and modulated by mutation of N201.

The Co-occurrence of Depressive Symptoms and Alcohol Use for Adolescent Boys and Girls: An Investigation of the Role of Self-Regulation and Approach Behavior

While many studies have been conducted on adolescent depressive symptoms and alcohol use, much of the research has examined these behaviors separately rather than examining their co-occurrence within individuals. In the present study, adolescents (N = 4412; 49% female) were surveyed at four time points (grade 9, 10, 11, and 12) and growth mixture modeling was used to identify groups of individuals reporting various patterns of depressive symptoms and alcohol use across the high school years. Four groups were identified, including co-occurrence (higher depressive symptoms and higher alcohol use relative to peers, comprising 6.1 % of boys and 7.1 % of the girls in the sample), pure depressive symptoms (higher depressive symptoms and lower alcohol use; 12.7% of boys and 12.5% of girls), pure alcohol use (higher alcohol use and lower depressive symptoms; 20.9% of boys and 19.9% of girls), and low co-occurrence (lower depressive symptoms and alcohol use, 60.3% of boys and 60.5% of girls). Groups were compared on self-regulatory (i.e., delay of gratification) and approach behaviors. For both boys and girls, delay of gratification was the strongest predictor of group membership, with the co-occurrence group scoring the lowest and the low co-occurrence group the highest. This finding emphasizes the importance of assessing delay of gratification in the identification of high risk youth.

Linking Ethical Leadership and Employees’ In-Role Performance: Exploring the Mediating Roles of Psychological Capital and Follower-Leader Relational Capital

This study investigates the mediating impact of psychological capital and follower-leader relational capital on the relationship between ethical leadership and in-role performance through the lenses of social exchange theory, social information processing theory, and psychological resources theory. Analysis of data collected from a sample of 171 employees and 24 supervisors from Pakistan reveals that ethical leadership has a positive effect on followers’ in-role job performance, yet this effect is fully explained through the role of psychological capital and partially through follower-leader relational capital. Significant implications of these findings for further research and practice are discussed.

Mirroring Enzymes: The Role of H-Bonding In HQuin-BAM Catalyzed Asymmetric Aza-Henry Reactions: A DFT Study into the Reactivity, Mechanism, and Origins of Selectivity

The exact mechanistic understanding of various organocatalytic systems in asymmetric reactions such as Henry and aza-Henry transformations is important for developing and designing new synthetic organocatalysts. The focus of this dissertation will be on the use of density functional theory (DFT) for studying the asymmetric aza-Henry reaction. The first part of the thesis is a detailed mechanistic investigation of a poorly understood chiral bis(amidine) (BAM) Brønsted acid catalyzed aza-Henry reaction between nitromethane and N-Boc phenylaldimine. The catalyst, in addition to acting as a Brønsted base, serves to simultaneously activate both the electrophile and the nucleophile through dual H-bonding during C-C bond formation and is thus essential for both reaction rate and selectivity. Analysis of the H-bonding interactions revealed that there was a strong preference for the formation of a homonuclear positive charge-assisted H-bond, which in turn governed the relative orientation of substrate binding. Attracted by this well-defined mechanistic investigation, the other important aspect of my PhD research addressed a detailed theoretical analysis accounting for the observed selectivity in diastereoselective versions of this reaction. A detailed inspection of the stereodetermining C-C bond forming transition states for monoalkylated nitronate addition to a range of electronically different aldimines, revealed that the origins of stereoselectivity were controlled by a delicate balance of different factors such as steric, orbital interactions, and the extent of distortion in the catalyst and substrates. The structural analysis of different substituted transition states established an interesting dependency on matching the shape and size of the catalyst (host molecule) and substrates (guest molecules) upon binding, both being key factors governing selectivity, in essence, offering an analogy to positive cooperative binding effect of catalytic enzymes and substrates in Nature. In addition, both intra-molecular (intra-host) and inter-molecular (host-guest, guest-guest) stabilizing interactions play a key role to the high π-facial selectivity. The application of dispersion-corrected functionals (i.e., ωB97X-D and B3LYP-D3) was essential for accurately modeling these stabilizing interactions, indicating the importance of dispersion effects in enantioselectivity. As a brief prelude to more extensive future studies, the influence of a triflate counterion on both reactivity and selectivity in this reaction was also addressed.

Intra- and inter-hemispheric interactions in somatosensory processing of pain : dynamical causal modeling analysis of fMRI data

La douleur est une expérience perceptive comportant de nombreuses dimensions. Ces dimensions de douleur sont inter-reliées et recrutent des réseaux neuronaux qui traitent les informations correspondantes. L’élucidation de l'architecture fonctionnelle qui supporte les différents aspects perceptifs de l'expérience est donc une étape fondamentale pour notre compréhension du rôle fonctionnel des différentes régions de la matrice cérébrale de la douleur dans les circuits corticaux qui sous tendent l'expérience subjective de la douleur. Parmi les diverses régions du cerveau impliquées dans le traitement de l'information nociceptive, le cortex somatosensoriel primaire et secondaire (S1 et S2) sont les principales régions généralement associées au traitement de l'aspect sensori-discriminatif de la douleur. Toutefois, l'organisation fonctionnelle dans ces régions somato-sensorielles n’est pas complètement claire et relativement peu d'études ont examiné directement l'intégration de l'information entre les régions somatiques sensorielles. Ainsi, plusieurs questions demeurent concernant la relation hiérarchique entre S1 et S2, ainsi que le rôle fonctionnel des connexions inter-hémisphériques des régions somatiques sensorielles homologues. De même, le traitement en série ou en parallèle au sein du système somatosensoriel constitue un autre élément de questionnement qui nécessite un examen plus approfondi. Le but de la présente étude était de tester un certain nombre d'hypothèses sur la causalité dans les interactions fonctionnelle entre S1 et S2, alors que les sujets recevaient des chocs électriques douloureux. Nous avons mis en place une méthode de modélisation de la connectivité, qui utilise une description de causalité de la dynamique du système, afin d'étudier les interactions entre les sites d'activation définie par un ensemble de données provenant d'une étude d'imagerie fonctionnelle. Notre paradigme est constitué de 3 session expérimentales en utilisant des chocs électriques à trois différents niveaux d’intensité, soit modérément douloureux (niveau 3), soit légèrement douloureux (niveau 2), soit complètement non douloureux (niveau 1). Par conséquent, notre paradigme nous a permis d'étudier comment l'intensité du stimulus est codé dans notre réseau d'intérêt, et comment la connectivité des différentes régions est modulée dans les conditions de stimulation différentes. Nos résultats sont en faveur du mode sériel de traitement de l’information somatosensorielle nociceptive avec un apport prédominant de la voie thalamocorticale vers S1 controlatérale au site de stimulation. Nos résultats impliquent que l'information se propage de S1 controlatéral à travers notre réseau d'intérêt composé des cortex S1 bilatéraux et S2. Notre analyse indique que la connexion S1→S2 est renforcée par la douleur, ce qui suggère que S2 est plus élevé dans la hiérarchie du traitement de la douleur que S1, conformément aux conclusions précédentes neurophysiologiques et de magnétoencéphalographie. Enfin, notre analyse fournit des preuves de l'entrée de l'information somatosensorielle dans l'hémisphère controlatéral au côté de stimulation, avec des connexions inter-hémisphériques responsable du transfert de l'information à l'hémisphère ipsilatéral.