Oxygen is one of the most important molecules in human beings. Our research is focused on how the human body can respond and adapt to the physiological challenge posed by a lack of oxygen. Ascorbic acid (Vitamin C) is one of the most important and considered the most effective water-soluble, chain-breaking antioxidant in human plasma, with the capacity to prevents damage by free radicals. This thesis presents four studies investigating the phenomenon of Reactive Oxygen Species (ROS) generation in the many different surgical conditions in the animal and in the human. Study one investigated the geometry and thermodynamic properties of vitamin C. Calculations were carried out at the restricted and unrestricted B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p) and B3LYP/EPR-II levels for two conformers (1 and 2) of L-ascorbic acid and their respective oxidation products to monodehydroascorbates of ab-initio methods by Gaussian O3W package. Conformer 1, free radical properties are compared with previously published calculations in the gaseous and aqueous solution states and with experimental EPR values. Calculated molecular structures, EPR (electron paramagnetic resonance spectroscopy), the vibration spectral and energetic properties and all are reported including some proposed changes to previous EPR assignments. Conformer 2 of L-ascorbic acid is predicted to have lower energy than Conformer 1, under the method and basis sets used, by between 11 and 26 kJ mol-1 and is stabilised by internal hydrogen bonding. Relaxed potential energy surface (PES) scans were carried out for two proton transfer processes and relative energies of stable minima and barriers between them determined. Hydrogen transfer is predicted in two systems with favourable spatial arrangements of O–H and O groups for which relaxed potential energy surface scans are reported. Calculated vibrational wavenumber values are provided for selected C=C, C=O, C–H and O–H modes assigned to particular groups and significant calculated EPR hyperfine coupling constants (HCC) values for splitting by H(1) and C(13) for radical species are also reported. These calculations contribute to a better understanding of the complex role of L-ascorbic acid and its various oxidised, neutral, ionic and radical forms in biochemistry and medicine. Study two examined if vitamin C could ameliorate the damaging effects of I-R on myocardium and we postulated that the mechanism of vitamin C protection against iii I-R-induced cell death involved quenching of ROS. In the vitamin C group after 5 min of reperfusion a significant, sudden increase of diastolic pressure in the heart was noted and reached a maximum of 77 mmHg after 12 min of reperfusion and then gradually decreased to 51 mmHg after 60 min of reperfusion period but was quicker than in Control group reaching 37 mmHg by the end of the reperfusion period. The level of A·− (ascorbate free radicals) sudden and massive increased at the time of reperfusion in the Vitamin C group. This increase was associated with poor mechanical function in hearts as indicated by the significantly depressed recovery process. After 30 min of global, now-flow ischaemia and 60min of reperfusion infarct size averaged 33% ± 1 in Control group and 30 % ± 1 in Vitamin C group, respectively, (P<0.05). There is strong evidence that oxygen centered radicals contribute to postischaemic dysfunction after global ischaemia. Our data unquestionably suggest that the large production of A·− was associated with a greater depression in myocardial contractile function, therefore could represent a marker of oxidative stress during I-R and could be related to the functional impairment during reperfusion. In summary, we have used the animal models of isolated heart perfusion to provide evidence that vitamin C did not reduce the infarct size, however “tendency” towards a decrease (↓) in infarct size with ascorbate and it protects from oxidative damage during global I-R as manifested by decreased concentrations of A·− and enhance recovery of mechanical function such as diastolic pressure and LVDP in postischaemic working rat hearts. Study three was designed to test the hypothesis that the physiological trauma associated with venous cannulation may artefactually stimulate systemic free radical formation in the acute phase that if not accounted for may under-estimate the oxidative stress response to exercise. The relationship between the time of venepuncture and the level of free radical generation during normoxic conditions was further investigated. The venous cannulation in Phase I, increased plasma A·− by 347 ± 173 AU/√G, P <0.05 after 2min of venepuncture with further increases observed after 5min and 10min of venous cannulation, respectively (403 ± 178 AU/√G; 462 ± 93 AU/√G, P < 0.05) vs baseline point time. After this time the level of A·− slightly blunted as to achieve a similar level to baseline point control after 30 minutes. In phase II the exerciseinduced increase in A·− was subsequently shown to be 48% greater (30min as opposed to the 2min post-cannulation resting baseline)(1754 ± 361 vs. 1979 ± 375 AU, P <0.05). Our findings demonstrate and confirm that venous cannulation per se stimulates iv the systemic formation of free radicals as an acute phase response which peaks at 10min and require approximately 15min to normalise. This has important interpretive implications for future studies that employ catheterisation. The final Study examined if the combination of exercise and inspiratory hypoxia would further compound regional tissue de-oxygenation that is frequently encountered during the ischaemic phase of surgery and thus, by consequence increase oxidative stress. The aim of the study was to further understand a potential relationship between oxidative stress and alterations in muscle oxygenation. Clear significant increases in the plasma concentration of A·− were detected in the peripheral blood of patients (normoxia(baseline) vs 6 data points of reperfusion after 5min of global ischaemic condition, P<0.05),(baseline vs immediate after ischaemia; 2337±525 vs 2633±508, AU, respectively). During global ischaemia the regional muscle oxygenation significantly decreased (↓∆O2Hb-oxyhaemoglobin), ↑∆HHb- deoxyhaemoglobin ), although increased regional blood volume (↑∆tHb- total haemoglobin). From the end of global ischaemia to 10 min after the regional muscle oxygenation progressively back to the start data point (↓∆HHb, ↑∆O2Hb). This study demonstrates for the first time that the I-R has got a big influence on the muscle oxygenation to increased ROS and the return of values towards baseline period in reperfusion stage appears to coincide with increased oxidative stress. Moreover, the present study has also demonstrated increased A·− level as early as the ischaemic phase of experiment independent of perioperative changes in the partial pressure of oxygen (pO2), elucidate a potentially important role for oxidative stress in provoking an appropriate vasodilation (NO-bioavailability) during the I-R period. This work demonstrates that; - Ascorbate is an antioxidant that can scavenge tissue and blood borne free radical, is essential in controlled amounts and is capable of initiating protective adaptation in the face of oxidative stress for the maintenance of physiological homeostasis. - Reperfusion is always associated with a sudden and massive release of ascorbate free radicals, with a maximal liberation within the first minutes of reperfusion. Vitamin C tended to reduce infarct size and protects from oxidative damage during global ischaemia and reperfusion. - The venous cannulation alone is enough per se stimulates the systemic formation of free radicals as a acute phase response. If this baseline artefact is not taken into account, the true magnitude of the exercise-induced oxidative stress response will be under-estimated. / The I-R has got a major influence on the muscle oxygenation to increased ROS and the return of values towards baseline period in reperfusion stage appears to coincide with increased oxidative stress. Using the state-of-the-art molecular techniques that include Electron Paramagnetic Spectroscopy (EPR) for the direct detection of free radicals and Near Infrared Spectroscopy (NIRS) for the direct detection of muscle oxygenation these studies have attempted to translate the basic mechanisms associated with free radical formation during I-R and have provided unique insight into the basic mechanisms responsible for the oxidative stress with the ultimate objective of developing novel antioxidant interventions that can provide effective prophylaxis.

Movement is an essential feature of life. It allows organisms to move towards a more favorable environment and to search for food. There are many biological systems that fall under the category active matter, from molecular motors walking on microtubules inside cells to flocks of birds. What these systems have in common is that each of its constituents converts energy into directed motion, that is, they propel themselves forward. Besides the many biological examples, there is also synthetic active matter, these are self-propelled particles made in a laboratory. These are typically colloidal sized particles that can propel themselves forward by self-phoresis. In this work the focus is on the low Reynolds number regime, meaning that the typical size of the constituents is less than a few micrometers. The models that are used to describe such active matter are can be viewed as nonequilibrium extensions to Brownian motion (the thermal motion of small particles dissolved in a fluid). In many systems the self-propulsion speed (activity) is not homogeneous in space: the particles swim faster in some areas than in others. The main topic of this dissertation is how a single active particle, or a few active particles tied together by a potential, behave in such systems. It is known that a single active particle without any steering mechanism spends most time in the regions where it moves slowly, or in other words, they spend most time in regions where they are less active. However, here it is shown that, even though they spend most time in the less active regions, dynamical properties, such as the probability to move towards the more active regions is higher than moving towards the less active regions. Furthermore, when the active particles are connected to a passive Brownian 'cargo' particle, chained together to form a colloidal sized polymer, or fixed to another active particle, the resulting active dimers or polymers either accumulate in the high activity regions or the low activity regions, depending on the friction of the cargo particle, the number of monomers in the polymer, or the relative orientation of active particles. Lastly, when the activity is both time- and space-dependent, a steady drift of active particles can be induced, without any coupling between the self-propulsion direction and the gradient in the activity. This phenomenon can be used to position the particles depending on their size.:1. Brownian Motion 2. Active Matter 3. Modeling Active Matter 4. Introduction: Inhomogeneous activity 5. Pseudochemotaxis 6. Cargo-Carrying Particles 7. Active Colloidal Molecules 8. Time-Varying Activity Fields Appendix: Hydrodynamics

Subsynchronous vibrations such as those caused by rotor instability represent one of the most harrowing scenarios of rotor vibration. They are related to a great diversity of destabilizing forces and some of them are not well understood yet. Therefore, special attention must be paid to this type of vibration. Active Magnetic Bearings (AMBs) monitor the position of the shaft and change the dynamics of the system accordingly to keep the rotor in a desired position, offering the possibility of being used as dampers for vibration control. In the present work, a single-disk and a three-disk rotor were built to evaluate the effectiveness of an Active Magnetic Damper (AMD) in damping subsynchronous vibrations. An AMD was used to inject a signal simulating a subsynchronous vibration in the rotor, as another AMD was used to perform active control. Two locations of the AMD were considered for each rotor. For the single-disk rotor, experimental data was taken with the AMD located at three-quarters of the rotor-span and with the AMD located at midspan. For the three-disk rotor, experimental data was taken with the AMD located at a quarter-span and with the AMD at two-thirds of the rotor span. An undamped critical speed and a forced response analysis were performed on the rotors in order to predict the dynamic characteristics of the rotors with and without the AMD. It was demonstrated that an AMD is effective in damping subsynchronous vibrations. The addition of an AMD introduces damping and stiffness to the rotor-bearing system resulting in a change in the synchronous response and a consequent increase of the amplitude of vibrations at synchronous frequencies. This effect must be carefully considered when designing a system with an AMD. / Master of Science

This thesis consists of research work in the broad area of soft condensed matter theory with a focus on active matter. The study of long wavelength, low frequency collective behavior of active particles (bacterial suspensions, fish schools, motor-microtubule extracts, active gels) forms an interesting modification to liquid-crystal hydrodynamics, in which the constituent particles carry permanent stresses that stir the fluid. Activity introduces novel instabilities and many novel aspects emerge. Our works focus on the dynamics, order, fluctuations and instabilities in these systems. In particular, we investigated the dynamics, order and fluctuation properties emerging from effective hydrodynamic descriptions of translationally ordered active matter and also studied those in microwave-driven quantum Hall nematics. We also investigated the rheological properties of active suspensions subjected to an applied orienting field. A summary of the works carried out is as follows. Translationally ordered active phases – active smectics and active cholesterics: Active or self-propelled particles consume and dissipate energy generating permanent stresses that stir the fluid around them. The collective behavior of systems of active particles, in systems with translational order, pose interesting questions and possibilities of new physics that differ strikingly from those in systems at thermal equilibrium with the same spatial symmetry. We developed the hydrodynamic equations of motion for (a) an active system with spontaneously broken translational symmetry in one direction, i.e., smectic and (b) the simplest uniaxially ordered phase of active chiral objects, namely, an active cholesteric. We analyze the fluctuation properties as well as the nature of characteristic instabilities that these systems can display and make a number of predictions. For example, in the case of an active smectic, we show that active stresses generate an effective active layer tension which, if positive, sup-presses the Landau-Peierls effect, leading to long-range smectic order in dimension d =3 and quasi-long-range in d =2, in sharp contrast with thermal equilibrium systems. Negative active layer tension in bulk systems, however, lead to a spontaneous Helfrich-Hurault undulation instability of the layers, accompanied by spontaneous flow. Also, active smectics, unlike orientationally ordered active systems, normally have finite concentration fluctuations. Similarly, for the case of cholesterics we show that cholesteric elasticity intervenes to suppress some of the instabilities present in active nematics. xi Numerical simulation of active smectics: We present results from a Brownian Dynamics simulation, with no hydrodynamic interaction, of a system of apolar active particles form-ing translational liquid-crystalline order in a suspension. The particles interact through a prolate-ellipsoidal Gay-Berne potential. We model activity minimally through different noise temperatures for movement along and normal to the orientation axis of each particle. We present preliminary results on the disruptive effect of activity on smectic order for the parameter values investigated. Future work will test the predictions of our theory [1] on active smectics. Rheology of active suspensions near field-induced critical points : Shear induces orientation of active stresses in a suspension, through flow alignment. Depending on the sign, activity then either enhances or reduces the viscosity. The change in viscosity, in the zero frequency limit, is proportional to the product of the magnitude of active stress and the system relaxation time. A strong enough orienting field can make the system approach a critical point and the relaxation time diverges. We show that, this results in the divergence of viscosity at zero frequency making the system strongly viscoelastic. Depending on the sign, activity strengthens or reduces the effect of the field. We also investigate the rheological property of an active suspension with mixed polar and nematic oreder. Active quantum Hall systems: We construct the hydrodynamic theory for a 2d charged active nematic with 3d electrostatics. We have investigated the interplay of the Coulomb interaction and activity in these systems. We show that activity competes to enhance the charge density fluctuations normally suppressed by long-ranged Coulomb interactions. The charge structure factor Sq of the corresponding passive charged nematic goes to zero as q, whereas in charged active nematics, activity leads to a nonvanishing charge structure factor at small wavenumber. We also show how the effect of an applied magnetic field can be incorporated into the dynamics of the system and leave scope for further studies on these effects.

Diss.--Mannheim, 2002. / Bibliogr. p. 195-212.

La chaîne Himalayenne est l'un des exemples les plus spectaculaires de déformation active à la surface de notre planète. Au cours des derniers siècles, de nombreux séismes majeurs (Mw > 7.5) ont affecté cette zone et le lourd bilan humain du séisme de Gorkha en 2015 a une nouvelle fois rappelé l’importance de parvenir à mieux estimer l’aléa sismique de cette région. Bien que les structures lithologiques et tectoniques semblent montrer au premier ordre une cylindricité le long des 2500 km de l'arc Himalayen, de nombreuses études, menées principalement au Népal, ont permis de mettre en évidence des variations latérales structurales, thermochronologiques, morphologiques, gravimétriques, sismologiques ou géodésiques. Le rôle de ces variations latérales sur la segmentation sismique reste cependant mal contraint. La taille maximale et la probabilité d’occurrence de ces méga-séismes sont donc toujours matière à débat.Ainsi, le comportement sismique de l’Himalaya du Bhoutan reste énigmatique. Pour certains les faibles taux de sismicité observés actuellement font de ce royaume une zone asismique de 350 km de long. Pour d’autres, à l’instar de l’Himalaya du Népal, la faible sismicité observée est associé à une forte accumulation de contrainte susceptible de générer des séismes majeurs. L'objectif de ce travail de thèse est d’améliorer notre connaissance de cette région en quantifiant la déformation à différentes échelles spatiales et temporelles via des études morphotectoniques et paléosismologiques.La première partie de cette thèse vise à quantifier les mouvements verticaux à l’ouest Bhutan et le long du Main Frontal Thrust, structure la plus frontale située au sud Bhoutan. Trois campagnes de terrain ont été réalisées permettant l'échantillonnage (1) de terrasses alluviales le long du front afin de quantifier et d'étudier les variations du soulèvement Holocène, (2) de bassins versants pour l'étude de la dénudation court-terme (< 20 ka) dérivée des cosmonucléides ($^{10}$Be) et (3) de terrasses alluviales dans le Moyen-Pays pour quantifier l’incision Holocène. Les vitesses verticales obtenues au front sont comparables à celle proposées le long du reste de l’arc himalayen, suggérant une cinématique relativement simple. Par contre, nos résultats indiquent une variation de la géométrie du chevauchement himalayen (Main Himalayan Thrust) entre l’est Népal et l’ouest Bhoutan.La seconde partie porte sur plusieurs études paléosismologiques le long du front ouest et centre Bhoutanais. Six sites différents ont été étudiés au cours de trois campagnes de terrain. La datation et la modélisation de charbons détritiques a permis de mettre en évidence l'occurrence d’au moins cinq séismes majeurs durant les derniers 2700 ans, faisant du Bhoutan une zone sismiquement aussi active que le Népal. A une échelle régionale, cette étude apporte donc de nouvelles contraintes et contribue au débat sur la possibilité d’occurrence d'un séisme de magnitude 9 le long de l'arc Himalayen. / The Himalayan arc is one of the most active intra-continental mountain belts in the world. Over the last centuries, several major earthquakes (Mw > 7.5) have struck this arc. The dramatic effects of the Gorkha earthquake sequence in 2015 pointed once again the crucial need to improve seismic hazard assessment of this area.Geological explorations of the Himalayas since the late 19th century have emphasized a 2500-km-long roughly cylindrical structure, with striking continuity of main units and thrust faults. However recent geophysical and geological investigations have revealed lateral variations. The relationship between these variations and earthquakes segmentation along the arc remains poorly constraint. The maximum size and the occurrence probability of such earthquakes are still a matter of debate.For instance, the seismic behavior of Bhutan remains enigmatic. The present-day low seismicity rate observed in this area can reflect two opposite fault behaviors: an aseismic creeping zone or a zone of stress accumulation for future great earthquakes as the others parts of Himalayas. The main objective of this thesis is to bring new constraints on the deformation of the Bhutan Himalayas, at different space- and time-scales, through morphotectonic and paleoseismological approaches.The first part of this thesis focuses on the vertical deformation assessment along a N-S transect in western Bhutan and along the Main Frontal Thrust, which is the southern-most thrust in southern Bhutan. In the past three years, we have carried out three fieldwork campaigns to sample (1) frontal terraces to assess Holocene uplift rates, (2) watershed basins to quantify short term denudation rates (< 20 ky) derived from cosmonuclides $^{10}$Be and (3) hinterland alluvial terraces to quantify the Holocene incision rate. Frontal Holocene uplift rates obtained in Bhutan are consistent with those obtained in the others parts of Himalayas. Furthermore, our results reveal a variation in the geometry of the Main Himalayan Thrust between eastern Nepal and western Bhutan.The second part focuses on several paleoseismic studies along the west and central bhutanese Himalayan front. Different sites were investigated during three fieldwork campaigns. Detritic charcoals sampling and modeling suggest the occurrence of at least five surface-rupturing earthquakes during the last ~2700 years. These results demonstrate that the present-day low seismicity rate observed in Bhutan is not representative of the seismic activity at longer time scale. At regional scale, they also take part of a broader discussion on the probability of occurrence of a magnitude 9 earthquake along the Himalayan arc.

Regression with L1-regularization, Lasso, is a popular algorithm for recovering the sparsity pattern (also known as model selection) in linear models from observations contaminated by noise. We examine a scenario where a fraction of the zero co-variates are highly correlated with non-zero co-variates making sparsity recovery difficult. We propose two methods that adaptively increment the regularization parameter to prune the Lasso solution set. We prove that the algorithms achieve consistent model selection with high probability while using fewer samples than traditional Lasso. The algorithm can be extended to a broad set of L1-regularized M-estimators for linear statistical models.

No description available.

Gilles Deleuze once famously stated that Spinoza’s remark that ”we do not know beforehand what a body can do” should be read as a cri de guerre against a philosophical tradition that ever since antiquity has devalued the role of the body in the formation of knowledge. This paper further investigates the role of the body in Spinoza’s Ethics by examining what I shall call the becoming-active of the body. Commentators often interpret activity as pertaining to the formation of rational thought through the so-called ”common notions” in the Ethics. However, in doing so, they often neglect the central role played by the body in the process of becoming active. Thinking, for Spinoza, is always ”in the midst of things”, and as such it must be interpreted according to the basic affective relationality of the body. The act of thought; the activity of thinking, must be understood as an expression of a more fundamental activity of the body if we are to remain true to the implications of Spinoza’s monistic ontology. The goal of this paper, then, is to show how the becoming-active of the body is a necessary correlate to the activity of the soul in the Ethics. By demonstrating this, I will show in the concluding sections of my investigation, how the role played by the body and affectivity in Spinoza’s philosophy forces us to reconsider not only ethics, but the activity of thinking in general.

There is always a need for easy-to-follow processes that enable accurate and non-time consuming solutions. Nowadays we see a lot of different approaches to development processes in software engineering. This project is concerned with how to manage a software development process in a reliable, secure and efficient way. Software is available which provides some help for project managers / administrators to work more productively, with effective communication. Using such systems, it is possible to keep track of all the phases of development, including task distribution, making maximum use of previous hands-on experience and increasing productivity, to deliver a finished product in minimum time. No existing solution, however, fulfills all the desirable criteria. This paper describes the motivation, design and implementation of an improved development management system using Active Server Pages and Microsoft Internet Information Services with a backend Microsoft Access Database developed using a waterfall software development process. The resulting system is described and evaluated. This system will be beneficial for software houses, because they can communicate on the web, allowing efficiency gains by avoiding the need to call meetings for distribution of tasks among employees, with the additional advantage of location-transparent team management through the Internet.