Proponents of mechanistic explanation have argued that dynamical models are mere phenomenal models, in that they describe rather than explain the scientific phenomena produced by complex systems. I argue instead that dynamical models can, in fact, be explanatory. Using an example from neuroscientific research on epilepsy, I show that dynamical models can meet the explanatory demands met by mechanistic models, and as such occupy their own unique place within the space of explanatory scientific models.

The aminoacyl-tRNA synthetases (aaRSs) are the universal set of enzymes responsible for attaching amino acids to tRNA to be used as substrates in the process of protein translation. As these enzymes act at the transition between nucleic acids and proteins, their specificity of action is critical for maintaining the fidelity of the genetic code. From a mechanistic standpoint, aaRS specificity is enforced by a complex series of tRNA structural and chemical elements that collectively make up its identity set and serve to distinguish one tRNA from another. Based on sequence, structure, and oligomeric differences, the aaRS family has been partitioned into two classes, each of which is responsible for roughly half of the 22 genetically encoded amino acids. In the studies presented here, pre-steady-state kinetic methods were employed to measure individual events that collectively make up the catalytic cycle of the class II Escherichia coli Histidyl-tRNA Synthetase (HisRS) in order to elucidate the nature of its enzymatic activity and determine how these events contribute to the exquisite specificity between enzyme and tRNA. The results presented here indicate indentiy elements of tRNAHis regulate the activity of the amino acid activation and aminoacyl transfer half reactions. Additional evidence suggests communication between active sites of the HisRS homodimer plays a role in establishing an alternating cycle of catalysis in the steady state.

Asphalt concrete mix design methods, such as the Marshall method, have historically been based on physical and phenomenological material testing empirically correlated to observed field performance. Changing pavement field state conditions such as increased trucking, poorer quality aggregate resources, and the aged state of road infrastructure in Saskatchewan have resulted in recent pavement performance to be outside traditional empirical performance prediction inference. <p>It has been recognized worldwide that a mechanistic based asphalt concrete mix design methodology that directly quantifies structural behaviour of pavement under diverse field state conditions could significantly assist pavement design engineers. However, SHRP Level II and III mechanistic asphalt concrete characterization has been shown not to be pragmatic for characterizing asphalt concrete mixes. <p>The objective of this research was to investigate the use of mechanistic material properties obtained from triaxial frequency sweep characterization in the rapid triaxial tester (RaTT) in conjunction with SHRP gyratory compaction properties for designing asphalt concrete for different asphalt cement contents, traffic loads, traffic speeds, and temperatures. <p>RaTT testing was more responsive to variation in asphalt cement content outside of acceptable ranges of volumetric properties relative to Marshall stability and flow. This demonstrated the importance of specifying acceptable volumetric properties of asphalt concrete mixes. Correlation of material properties with volumetric measurements validated triaxial frequency sweep characterization in the RaTT. Dynamic modulus, Poissons ratio, and phase angle results were in accordance with expected material behaviour, indicating that the RaTT provides reasonable asphalt concrete material properties. Also, the RaTT identified asphalt concrete to be a nonlinear viscoelastic material, as observed in the field. <p>The RaTT was able to characterize SHRP gyratory compacted samples for the typical range of traction states, load frequencies, and temperatures that simulated a range of Saskatchewan field state conditions. Triaxial frequency sweep testing in the RaTT could significantly augment conventional volumetric mix analysis as well as the SHRP SuperpaveTM Level I asphalt concrete mix design system. RaTT testing was found to be cost effective, time efficient, and provided mechanistic material constitutive relations that can be employed for inelastic mechanistic mix design, road structural modelling, and asset management.

Asphalt concrete mix design methods, such as the Marshall method, have historically been based on physical and phenomenological material testing empirically correlated to observed field performance. Changing pavement field state conditions such as increased trucking, poorer quality aggregate resources, and the aged state of road infrastructure in Saskatchewan have resulted in recent pavement performance to be outside traditional empirical performance prediction inference. <p>It has been recognized worldwide that a mechanistic based asphalt concrete mix design methodology that directly quantifies structural behaviour of pavement under diverse field state conditions could significantly assist pavement design engineers. However, SHRP Level II and III mechanistic asphalt concrete characterization has been shown not to be pragmatic for characterizing asphalt concrete mixes. <p>The objective of this research was to investigate the use of mechanistic material properties obtained from triaxial frequency sweep characterization in the rapid triaxial tester (RaTT) in conjunction with SHRP gyratory compaction properties for designing asphalt concrete for different asphalt cement contents, traffic loads, traffic speeds, and temperatures. <p>RaTT testing was more responsive to variation in asphalt cement content outside of acceptable ranges of volumetric properties relative to Marshall stability and flow. This demonstrated the importance of specifying acceptable volumetric properties of asphalt concrete mixes. Correlation of material properties with volumetric measurements validated triaxial frequency sweep characterization in the RaTT. Dynamic modulus, Poissons ratio, and phase angle results were in accordance with expected material behaviour, indicating that the RaTT provides reasonable asphalt concrete material properties. Also, the RaTT identified asphalt concrete to be a nonlinear viscoelastic material, as observed in the field. <p>The RaTT was able to characterize SHRP gyratory compacted samples for the typical range of traction states, load frequencies, and temperatures that simulated a range of Saskatchewan field state conditions. Triaxial frequency sweep testing in the RaTT could significantly augment conventional volumetric mix analysis as well as the SHRP SuperpaveTM Level I asphalt concrete mix design system. RaTT testing was found to be cost effective, time efficient, and provided mechanistic material constitutive relations that can be employed for inelastic mechanistic mix design, road structural modelling, and asset management.

Undoubtedly, the advancement of IoT technology has created a plethora of new applications and a growing number of devices connected to the internet. Among these developments emerged the novel concept of smart farming. In this context, sensor nodes are used in farms to help farmers acquire a deeper insight into the environmental factors affecting their productivity. In recent years, we have witnessed an emerging trend of scholarly literature focused on smart farming. Some focus has been on system architecture for monitoring purposes, while another area of interest includes yield prediction. Humidity, air and soil temperature, solar radiation, and wind speed are some key weather elements monitored in smart farms. We introduce a mechanistic crop growth model to predict crop growth and subsequent yield, subject to weather, soil parameters, crop characteristics and management practices. We also seek to measure the influence of nitrogen on yield throughout the growing season. The machine learning models are trained to emulate the crop growth model in the state of Iowa (US). The multilayer perceptron (MLP) is chosen to evaluate the model prediction as it generates fewer errors. Furthermore, the MLP optimization model is used to maximize corn yield. The experiment was performed using different scenarios, stochastic gradient descent (SGD), and adaptive moment estimation (Adam) optimizers. The experiment results revealed that the SGD optimizer and the dataset with the scenario of unchanged parameters provided the highest crop yield compared to the mechanistic crop growth model.

<p> It had been proposed that α-hydroperoxydiazenes decompose by the radical chain abstraction of the hydroxy group. This suggested that these compounds could be used as hydroxyalkylating agents for unsaturated systems. </p> <p> Compounds 15 and 23 were prepared by the autoxidation of the corresponding hydrazone. α-Hydroperoxydiazenes 15 and 23 were used to hydroxyalkylate ethyl vinyl ether and 2-methoxypropene in yields of 62-65%. Mechanisms of the addition reaction are discussed. </p> <p> In an attempt to alkylate a hetero atom system, ·compound 15 was thermolyzed with compound 25. The alkylation product was not obtained. </p> <P> Compound 15 was converted to α-hydroxydiazene 34 by the action of Φ3P. α-Hydroxydiazine have been used synthetically in the hydroalkylation of alkenes. The rate constant of hydrogen abstraction was determined to be in the range of 1.5 x 10^5 M^-ls^-l to 1.5 x 10^7 M^-ls^-l by the use of a radical clock reaction. An upper limit on the rate of rearrangement of the 2-cyanopropyl radical was found to be 3.65 x 10^3 s^-1 . </p> A new compound (23) was prepared / Thesis / Master of Science (MSc)

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No description available.

The purpose of this study was to assess the operations of smallholder sugar cane grower organisations based in the Komati River Basin of Swaziland. These organisations were formed at the beginning of this millennium. Some ten years later some have performed very well while others are struggling, and yet others are on the verge of collapse. The situation for some of these became so bad that their sustainability in the business was challenged. This did not augur well for the Government of Swaziland that established the project to address the issues of food security and poverty alleviation. This study was conducted as a case study with five organisations forming the cases. Data were collected from three levels within each organisation using primary and secondary data sources. Findings revealed that organisations were alike in many aspects including history, governance, strategic and human resource management. This was not surprising because for all of them capacity building is provided by Swaziland Water and Agriculture Development Enterprise (SWADE), Swaziland Sugar Association (SSA), and Mhlume Sugar Mill. Organisational structures were bureaucratic with limited participation in decision-making by employees and strict adherence to procedures and specialisation. This led to the conclusion that a mechanistic organisation management system was in place. Environmental resources were favourable according to chairpersons and their views were that they have the self-confidence and commitment for entrepreneurial development. The study concluded that a new series of studies need to be undertaken to explore the many unique research areas that are unearthed. Studies could narrow the focus but as far as possible consider the whole population of organisations in the K1DDP (19). Organisations also need to consider improving management and networking to reduce transaction costs.

Mon projet de thèse a été dédié à l’étude des synucléinopathies. Ces maladies neurodégénératives sont caractérisées par la présence d’inclusions intracytoplasmiques positives pour l’alpha-synucléine et contenues dans les neurones pour la maladie de Parkinson (i.e. les corps de Lewy) ou dans les oligodendrocytes pour l’atrophie multisystématisée (i.e. les inclusions cytoplasmiques oligodendrogliales). L’objectif de mon travail de thèse fut de proposer une approche multifactorielle et translationnelle en développant les aspects de modélisation, de mécanistiques et de thérapeutiques associées aux synucléinopathies. Nous nous sommes tout d’abord intéressés à disséquer les mécanismes sous-jacents à la neurodégénérescence induits par la protéine alpha-synucléine dans un modèle primate non-humain de la maladie de Parkinson. Nous avons ainsi souligné le rôle toxique de la protéine alpha-synucléine et mis en lumière de nouveaux processus cellulaires impliqués dans le phénomène de neurodégénérescence. Dans ce même modèle animal, nous avons étudié l’hypothèse d’une propagation de la pathologie induite par l’alpha-synucléine entre les systèmes nerveux centraux et périphériques. Nous avons ainsi pu démontrer l’existence d’une route bidirectionnelle de propagation et de neurodégénérescence de la protéine entre les deux systèmes nerveux, pouvant corroborer la présence de symptômes non moteurs précoces au cours de la pathologie. Enfin, nous nous sommes concentrés sur le rétablissement de la fonction autophagique comme cible thérapeutique commune aux synucléinopathies. Nous avons ainsi pu démontrer qu’une restauration de la machinerie de dégradation de la voie autophagie était suffisante pour rétablir les taux physiologiques de la protéine alpha-synucléine et induire une neuroprotection dans un modèle rongeur de la maladie de Parkinson et d’atrophie multi-systématisée. Ces travaux corroborent le rôle clé de la protéine alpha-synucléine dans l’étiologie des synucléinopathies et proposent de nouvelles stratégies thérapeutiques communes à toutes les synucléinopathies afin de rétablir les niveaux physiologiques cellulaires de la protéine et une neuroprotection au sein du système nerveux central. / My thesis project was dedicated to the study of synucleinopathies. Synucleinopathies are neurodegenerative diseases characterized by the presence of alpha-synuclein positive intracytoplasmic inclusions which are present either in neurons for Parkinson’s disease (i.e. Lewy Bodies) or in oligodendrocytes for Multiple system atrophy (i.e. Glial Cytoplasmic Inclusions). The aim of my work was to establish a multifactorial and translational approach through modeling, mechanistic and therapeutic aspects associated with synucleinopathies. First, we focused on dissecting the underlying alpha-synuclein-mediated mechanisms of neurodegeneration using a non-human primate model of Parkinson’s disease. We confirmed the toxic role of alpha-synuclein in the pathology and highlighted unpredictable cellular processes involved in neurodegeneration. Using the same Parkinson’s disease model, we studied the hypothesis of a pathological propagation between the central and peripheric nervous systems in an attempt to decipher the initiation point and the direction of propagation of the associated pathology. We thus demonstrated a bidirectional route of propagation of alpha-synuclein between the CNS and the ENS and within the ENS. Finally, we focused on the restoration of the autophagic function as a potential common therapeutic target for all synucleinopathies. We demonstrated through a gene-based restoration of the autophagy, we efficiently reestablish alpha-synuclein physiological protein levels, while inducing neuroprotection in a Parkinson’s disease and Multiple system atrophy rodent models. Thus, this work corroborates the key role of alpha-synuclein in the etiology of synucleinopathy and offers new common therapeutic strategies for all synucleinopathies to decrease alpha-synuclein-induced toxicity into the central nervous system.