A machining process is one of the most common techniques used to remove material in order to create a final product. Most studies on mechanisms of cutting are performed under the assumption that the studied material is isotropic, homogeneous and continuous. One important feature of material- its anisotropyis linked to its crystallographic nature, which is usually ignored in machining studies. A crystallographic orientation of a workpiece material exerts a great influence on the chip-formation mechanism. Thus, there is a need for developing fundamental understanding of material's behaviour and material removal processes. While the effect of crystallographic orientation on cutting-force variation is extensively reported in the literature, the development of the single crystal machining models is somewhat limited.

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La vision classique et hiérarchique de l’organisation du système moteur est remise en question par la découverte d’autres structures que le cortex moteur primaire capables d’influer en parallèle sur la sortie motrice, dans le cadre d’un modèle hodotopique. L’objectif de ce travail a été d’étudier les réseaux de contrôle du mouvement à l’aide de stimulations électriques directes cérébrales lors de chirurgies en condition éveillée pratiquées pour l’exérèse de tumeurs cérébrales. Cette méthode permet la préservation de la fonction motrice tout en apportant de nombreuses informations sur l’organisation du système moteur en général. Le contrôle moteur a été étudié au travers du phénomène moteur négatif, qui consiste en un arrêt du mouvement sans perte de tonus ou de conscience lors d’électrostimulations. Décrit initialement au niveau cortical, nos travaux ont montré qu’il était possible d’identifier ce phénomène dans la substance blanche de façon bilatérale et que les fibres supportant ces réponses motrices négatives sont organisées d’une manière somatotopique, à l’instar de la voie pyramidale. Nous avons pu mettre en évidence une voie modulatrice motrice bilatérale capable d’inhiber les mouvements des deux membres supérieurs lors d’une stimulation sous-corticale unilatérale. Nous avons montré qu’une lésion des sites générant des réponses motrices négatives conduisait à un syndrome de l’aire motrice supplémentaire et à des troubles définitifs des mouvements fins et de la coordination bimanuelle. Ces résultats expliquent les troubles observés lors de chirurgies des régions prémotrices réalisées sans cartographie motrice active, c’est-à-dire cherchant uniquement à identifier les structures motrices primaires. Ils valident la nécessité de pratiquer une cartographie motrice en condition éveillée et ce quelle que soit la dominance hémisphérique. Ces résultats à l’échelle sous-corticale nous ont conduit à définir le concept de réseau moteur négatif et son implication dans les réseaux de contrôle moteur. Le preuve de l’existence de tels réseaux nous a permis d’explorer le niveau cortical et de mettre en évidence une organisation systématique des aires motrices négatives, proposant ainsi une autre vision que celles d’une répartition aléatoire ou somatotopique. Cette organisation en plusieurs aires effecteurs-dépendantes et redondantes a permis de confirmer par les stimulations électriques directes la ségrégation du gyrus précentral en plusieurs gradient rostro-caudal et dorso-ventral. L’ensemble de ces éléments nous a permis d’émettre plusieurs hypothèses concernant le rôle de ces réseaux. Nous supposons qu’il s’agit de plusieurs réseaux interconnectés fonctionnant à l’aide de mécanismes inhibiteurs internes, dont le rôle va de la modulation du flux moteur dans le cadre de processus décisionnels compétitifs intégrés aux aires négatives à l’inhibition vraie d’un comportement moteur dans le cadre de circuits entre le cortex et les noyaux gris centraux. La carte probabiliste réalisée permettra de planifier les chirurgies cérébrales mais aussi de servir de zone d’intérêt pour les nouvelles thérapies par stimulations et la recherche en neurosciences. / The classical and hierarchical view of the motor system has been challenged since the discovery of other structures able to modulate the motor output in the framework of a hodotopic model. The aim of this work was to study the motor control network thanks to direct electrostimulations performed during awake surgery for brain tumors. This method has shown its effectiveness to preserve motor functions while giving new highlights about the organization of the motor system. In our work, motor control has been studied through the negative motor phenomenon, which consists in a complete arrest of movement without loss of tonus or consciousness during electrostimulations. Initially described at a cortical level, our work demonstrated the possibility to elicit negative motor phenomenon in both hemispheres at a subcortical level. Moreover, we identified a bilateral modulatory motor pathway able to inhibit both upper limbs during unilateral subcortical stimulations. We also shown that fibers driving negative motor responses are organized in a somatotopic manner, like the pyramidal pathway. Resection of these fibers lead to a supplementary motor area syndrome with permanent deficit in fine motor skills and bimanual coordination. These results explain the neurological deficits which might occur after surgery in premotor areas when no active brain mapping is performed, that is, when only primary motor structures are sought. They emphasize the necessity to perform a motor mapping during awake surgery whatever the side and hemispheric dominance. These subcortical results led us to define the concept of negative motor networks and their involvement in motor control networks. Evidences of this network allowed us to explore the cortical level and to report a well-defined organization of the negative motor area, different from the random or somatotopic distributions previously described. This effector-dependent and redundant organization in several areas defined by direct electrostimulations has been helpful to confirm the rostro-caudal and dorso-ventral segregation of the precentral gyrus. Consequently, it was possible to propose several hypothesis about the role of these networks. We presume that they are constituted by several large-scale interconnected networks, based on internal inhibitor mechanisms, whose role goes from modulation of the motor output in a competitive model of decision-making integrated in the negative motor area to real inhibition of motor behaviors thanks to cortico-basal ganglia circuitry. The probabilistic map created with these works will be helpful to plan surgery but could also provide regions of interest for brain stimulations therapies as well as neuroscientific research.

One feature of the brain is that different parts of it respond to different stimuli. This means not all brain regions or neurons within those regions are active at a given moment. This feature of the brain gives it the ability to encode and store a wide range of stimuli that are then used to make predictions about a changing external environment. Activation of non-overlapping neural populations is fundamental to the ability to encode a wide range of stimuli to represent a changing environment. To examine the limits of this idea we used genetic tools to label active cell populations following a neutral stimulus presentation or a learned negative association with the same stimulus. The study examined the degree of similarity between these active populations by comparing key features of the active neurons including gene expression and monosynaptic inputs. Another feature of the brain is its ability to store information. In a neural population recently activated by a salient stimulus, molecular processes occur that result in the formation and maintenance of a memory. Collectively these processes are referred to as plasticity, and act on short and long time scales to strengthen the connections between active neurons and weaken the connections between inactive ones. Plasticity processes are not only necessary for the formation and storage of memories but also for wiring up the nervous system during development. A molecule called ZIP has been shown to erase memories months after formation and specifically affects plasticity on longer time scales. However, the effects of ZIP on the developing brain are not well understood and difficult to study using ZIP’s typical delivery method of injection into the brain. To facilitate a developmental study of ZIP’s effects, we made a genetic tool that can specify where and when ZIP is delivered to the brain. Results of the study indicated that males were particularly vulnerable to ZIP during early development while females were unaffected. Together these results provide insight into the limits of information coding potential at the anatomical level and reveal a fundamental difference in plasticity processes in males and females. / 10000-01-01

The genetic causes of intellectual disability (ID) and autism spectrum disorder (ASD) are frequently associated with mutations in genes that encode synaptic proteins. A recent screen of ID patients has revealed that approximately 4% of individuals carry spontaneous autosomal-dominant de novo mutations in the SYNGAP1 gene. This gene encodes the synaptic GTPase activating protein (SYNGAP) a known regulator of Ras signalling. Investigations into the pathological consequences of Syngap1 haploinsufficiency (Syngap+/−) in mice have reported abnormalities in behaviour, synaptic plasticity and dendritic spine development. These are analogous to findings from the mouse model of fragile X syndrome (FXS; Fmr1-/y), the most common inherited form of ID. One of the prominent phenotypes reported in the mouse model of FXS is that a form of hippocampal long-term depression (LTD) mediated by the activation of Group 1 (Gp1) metabotropic glutamate (mGlu) receptors is enhanced and independent of new protein synthesis (Huber et al. 2002; Nosyreva et al. 2006). The cause of these synaptic plasticity deficits together with other cognitive abnormalities observed in FXS are thought to arise, in part, from excessive protein synthesis, the consequence of altered mGlu5 receptor signalling via the Ras-ERK1/2 signalling pathway. Enhanced protein synthesis rates in Fmr1-/y mice can be corrected by either inhibiting mGlu5 receptors or reducing Ras and subsequent ERK1/2 activity (Osterweil et al. 2013). In this thesis mGluR-dependent LTD was examined at Schaffer collateral/commissural inputs to CA1 pyramidal neurones in hippocampal slices obtained from Fmr1-/y, Syngap+/− and Fmr1-/ySyngap+/− double mutant mice. Extracellular field recordings reveal that acute application of the Gp1 mGluR agonist dihydroxyphenylglycine (DHPG) induces a form of mGluR-dependent LTD that is enhanced and independent of new protein synthesis in CA1 of Fmr1-/y mice. In Syngap+/− mice, the magnitude of mGluR-dependent LTD is also significantly increased relative to WT littermates and insensitive to protein synthesis inhibitors. Furthermore, in the Fmr1-/ySyngap+/− double mutant, Syngap haploinsufficiency occludes the increase in mGluR-dependent LTD caused by the loss of FMRP. In addition, metabolic labelling studies reveal basal protein synthesis rates to be modestly enhanced in the hippocampus of Fmr1-/y mice compared to WT mice. Importantly this phenotype translates to the rat model of FXS. In Syngap+/- hippocampal slices, basal protein synthesis rates are also significantly elevated compared to WT counterparts. Interestingly, elevated basal protein synthesis rates in Syngap+/- mice could be corrected in the hippocampus by similarly pharmacological strategies employed in Fmr1-/y mice. The comparable neuropathophysiology we observe between Syngap+/− and Fmr1-/y mice suggests that SYNGAP and fragile X mental retardation protein (FMRP) may converge on similar biochemical pathways raising the intriguing possibility that therapeutic strategies used in the treatment of FXS may also be of benefit in treating individuals with ID caused by mutations in SYNGAP1.

In this paper we have introduced a concept of analyzing the performance of dynamic network organization (NO) in response to multiple input objectives of network organization (NO) and input set of unpredictable external environment, and we have correlated plasticity of NO with this performance measure. A three stage conceptual model of the process has been described which comprised of dynamic system of multi-agent network, multiple objectives and input goals of network driver (S n), unpredictable external environment (ϵ). Dynamic system of the network organization takes through its two phase and processes this based on time and system response variables. Processing of input information by the system variables gives a ratio of system response variable and input. Further analysis is based on the value of this performance values. This model suggests a performance measuring technique which takes an input set of objectives from network driver of the NO, a set of input from external environment (ϵ) state and processes this input based on the existing state of the dynamic system in the NO. This process output shows dynamic system performance in dynamic environment and how this performance coefficient correlates with the Plasticity of network organization. We have presented several examples, mathematical models and graph by analyzing true scenarios on UAV patrolling zone.

Earthquakes are natural calamities that occur as a result of sudden release of strain energy stored in fault planes. Earthquakes have been observed to cause huge damage to infrastructures and lives. Earthquakes result in development of fissures, abnormal or unequal movement of foundations, and loss of strength and stiffness of the soils. Liquefaction is attributed as a major cause for the loss of strength and stiffness of soil during earthquakes. In the past, liquefaction was attributed only to coarse-grained to medium-grained sand and was extensively studied but the fine-grained soils were generally considered as non-liquefiable. However, from observations during recent earthquakes, fine-grained soils having low plasticity (plasticity index (PI) <20) have experienced ground failures due to liquefaction or large deformations. Moreover, laboratory experiments show that not only saturated cohesionless soils but also fine-grained soils may liquefy if certain criteria are met. One of the parameters which influences the liquefaction characteristics of fine-grained soils is its plasticity. This study may become helpful in understanding the effect of plasticity on liquefaction resistance of fine-grained soils. The objective of this study were to investigate the (1) effect of plasticity on pore pressure built up and deformation characteristics of fine-grained soils, and (2) effects of cyclic shear stress on liquefaction resistance of fine-grained soils. A total of 24 tests were conducted using a stress controlled cyclic triaxial testing machine on identically prepared specimens at an initial effective confining pressure of 5.0psi. The plasticity index (PI) was varied from non-plastic (NP) to 14.53. Sil-Co-Sil #40, a non-plastic commercial silt (product of US Silica Company) and EPK Kaolin clay (product of Edgar Minerals Inc.) were used as base materials. These materials were mixed in different proportions to obtain desired plasticity index. Out of the twenty-four tests, eleven tests were conducted on clean silt samples. Among the tests on clean silt samples, four tests were conducted on specimens having a post consolidation void ratio of 0.74 to 0.76. Further, six tests were conducted on specimens having a post consolidation void ratio of 0.74 to 1.04 by using a cyclic stress ratio (CSR) of 0.2 and 0.25. Seventeen tests were grouped to study the influence of plasticity on liquefaction characteristics of fine-grained soil. The PI of specimens tested ranged from non-plastic (NP) to 14.53. Each of the specimens with a definite PI was tested at an initial confining pressure of 5.0 psi using a CSR of 0.2, 0.3, and 0.4. The results obtained from the tests were used to compare the effects of plasticity on liquefaction characteristics of fine-grained soils. Based on the limited tests conducted, it was observed that plasticity index had distinct influence on the cyclic strength of the samples. It was found that CSR required to cause a pre-determined strain in a given number of loading cycles reduces as the plasticity index increases from non-plastic (NP) to 3.46, but increases for soils having PI greater than 3.46. Moreover, the liquefaction resistance decreases with the increase in cyclic shear stress for all soils regardless of plasticity indices (PIs). The critical PI value corresponds to 15% of EPK clay content in the specimen which gives a PI of 3.46.

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Training locomotor pattern generating networks (CPGs) with body weight supported treadmill training or through arm and leg cycling improves walking in chronic stroke. These outcomes are presumed to result from enhanced interlimb connectivity and CPG function. The extent to which rhythmic arm training activates interlimb CPG networks for locomotion remains unclear and was assessed by studying chronic stroke participants before and after 5-weeks of arm cycling training. Strength was assessed bilaterally via maximal voluntary isometric contractions in the legs and hands. Muscle activation during arm cycling and transfer to treadmill walking were assessed in the more affected (MA) and less affected (LA) sides via surface electromyography. Changes to interlimb coupling during rhythmic movement were evaluated using modulation of cutaneous reflexes elicited by electrical stimulation of the superficial radial nerve at the wrist. Bilateral soleus stretch reflexes were elicited at rest and during 1Hz arm cycling. Clinical function tests assessed walking, balance and motor function. Results show significant changes in function and neurophysiological integrity. Training increased bilateral grip strength, force during MA plantarflexion and muscle activation. ‘Normalization’ of cutaneous reflex modulation was found during arm cycling. There was enhanced activity in the dorsiflexor muscles on the MA side during swing phase of walking. Enhanced interlimb coupling was shown by increased modulation of MA soleus stretch reflexes amplitudes during arm cycling after training. Clinical evaluations showed enhanced walking ability and balance. These results are consistent with training-induced changes in CPG function and interlimb connectivity and underscore the need for arm training in the functional rehabilitation of walking after neurotrauma. / Graduate

abstract: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by developmental delays, intellectual disabilities, impaired language and speech, and movement defects. Most AS cases are caused by dysfunction of a maternally-expressed E3 ubiquitin ligase (UBE3A, also known as E6 associated protein, E6-AP) in neurons. Currently, the mechanism on how loss-of-function of the enzyme influences the nervous system development remains unknown. We hypothesize that impaired metabolism of proteins, most likely those related to E6-AP substrates, may alter the developmental trajectory of neuronal structures including dendrites, spines and synaptic proteins, which leads to disrupted activity/experience-dependent synaptic plasticity and maturation. To test this hypothesis, we conducted a detailed investigation on neuronal morphology and electrophysiological properties in the prefrontal cortex (PFC) layer 5 (L5) corticostriatal pyramidal neurons (target neurons). We found smaller soma size in the maternal Ube3a deficient mice (m-/p+; 'AS' mice) at postnatal 17-19 (P17-19), P28-35 and older than 70 days (>P70), and decreased basal dendritic processes at P28-35. Surprisingly, both excitatory and inhibitory miniature postsynaptic currents (mEPSCs and mIPSCs) decreased on these neurons. These neurons also exhibited abnormalities in the local neural circuits, short-term synaptic plasticity and AMPA/NMDA ratio: the excitatory inputs from L2/3 and L5A, and inhibitory inputs from L5 significantly reduced in AS mice from P17-19; Both the release probability (Pr) and readily-releasable vesicle (RRV) pool replenishment of presynaptic neurons of the target neurons were disrupted at P17-19 and P28-35, and the change of RRV pool replenishment maintained through adulthood (>P70). The AMPA/NMDA ratio showed abnormality in the L5 corticostriatal neurons of PFC in AS mice older than P28-35, during which it decreased significantly compared to that of age-matched WT littermates. Western Blot analysis revealed that the expression level of a key regulator of the cytoskeleton system, Rho family small GTPase cell division control protein 42 homolog (cdc42), reduced significantly in the PFC of AS mice at P28-35.These impairments of synaptic transmission and short-term synaptic plasticity may account for the impaired neuronal morphology and synaptic deficits observed in the PFC target neurons, and contribute to the phenotypes in AS model mice. The present work reveals for the first time that the E6-AP deficiency influences brain function in both brain region-specific and age-dependent ways, demonstrates the functional impairment at the neural circuit level, and reveals that the presynaptic mechanisms are disrupted in AS model. These novel findings shed light on our understanding of the AS pathogenesis and inform potential novel therapeutic explorations. / Dissertation/Thesis / Doctoral Dissertation Neuroscience 2017