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Based on the success of diacyl-tert-butylhydrazines RH-5849 and RH-1266 in controlling agricultural crop pests, we endeavored to synthesize our own diacylbenzyl- and arylhydrazine derivatives for use against the malaria vector Anopheles gambiae. In the process of producing a library of compounds for assay against An. gambiae, it became clear that employing regioselective acylation techniques (in molecules that feature two nucleophilic, acyclic nitrogen atoms α to one another) would be imperative. Synthesis of the library derivatives proceeded rapidly and after topical assay, we found three compounds that were more toxic than the RH-series leads. One of the three displayed an LD50 value of half that of RH-1266, though patch clamp assay concluded that toxicity was not necessarily linked to inhibition of mosquito K+ channel Kv2.1. The acylation of monoarylhydrazines appears simple, but its regioselectivity is poorly understood when assumed as a function of basicity correlating to nucleophilic strength. We determined the ratio of the rate constants for distal to proximal N-acylation using 19F NMR spectroscopic analysis of reactions of 4-fluorophenylhydrazine with limiting (0.2 equiv) acylating agent in the presence of various bases. Acid anhydrides gave consistent preference for distal acylation. The selectivity of acylation by acyl chlorides when using pyridine gives strong distal preference, whereas use of triethylamine or aqueous base in conjunction with aroyl chlorides showed a moderate preference for proximal acylation. This observation yielded a convenient one-step method to synthesize proximal aroylarylhydrazines in yields comparable or superior to that provided by the standard three-step literature approach. Combined with NMR evidence of the distal nitrogen as the unambigiously stronger base of the two nitrogens, we propose a single electron transfer mechanism that predicts the regiochemistry of arylhydrazines toward acylating agents better than the nucleophilicity model based on pKa values. While synthesizing the acylhydrazine library for assay against An. gambiae, NMR spectroscopy revealed rotational isomerisms of two types: chiral helicity (M)/(P) and acyl (E)/(Z)-isomerism due to hindered rotation. Variable temperature NMR allowed the measurement of N-N bond rotational barriers, as well as estimate the barrier of (E)/(Z) interconversion. We obtained the X-ray crystal structures of four diacylhydrazines to test this hypothesis and revealed both the twist conformation around the N-N bond axis and (E)/(Z)-isomerism around the proximal acyl group. Computation (which agreed with the crystal structures) allowed us to estimate which (E)/(Z)-isomers were most likely being observed in solution at room temperature by NMR spectroscopy. In addition, we were able to calculate transition structures corresponding to N-N bond rotational barriers of (E,Z)- and (Z,Z)-isomers of model molecules and rationalize the difference in coalescence temperatures between (E,Z)- and (Z,Z)-isomers. / Ph. D. / Herein we present the work of both synthesizing and characterizing the mosquitocidal and chemical properties of acylhydrazines. Part of the challenge of working with hydrazines comes in part from deceptive comparisons to amines and ammonia; hydrazine is as different from ammonia as hydrogen peroxide is from water. We were successful in identifying effective synthetic techniques to obtain our desired acylhydrazines reliably and managed to discover compounds that were better at eliminating <i>Anopheles gambiae</i> (the african malaria mosquito vector) than lead compounds from previous researchers. In the process of making the library of compounds for mosquito testing, we explored hydrazine reactivity toward acylating agents in a direct and deeper way than previous work, as well as their dynamic structural features. We employed a battery of techniques, including NMR, X-ray crystallography, and computational molecular modeling to understand these molecules and possibly contribute insight into their biochemical efficacy.

La description magnétohydrodynamique est utilisée pour étudier les plasmas de fusion par confinement magnétique dans deux configurations: tokamak et reversed field pinch. Une méthode de Fourier pseudo-spectrale et une technique de pénalisation en volume sont employées pour résoudre les équations. La méthode de pénalisation permet d’introduire des conditions aux limites de Dirichlet et donc de faire varier facilement la géométrie considérée. Les simulations dans des géométries toroïdales de type tokamak montrent l’apparition spontanée de vitesses. Une importante composante toroïdale se développe si le système est peu dissipatif. Il est aussi montré que la brisure de symétrie dans la forme de la section du tore fait apparaitre un moment angulaire toroïdal. Pour le Reversed Field Pinch on montre l’émergence de structures hélicoïdales. La forme de ces structures varie en fonction des coefficients de transport ainsi que du paramètre de pincement du champ magnétique imposé. Pour compléter l’étude on compare les résultats du tore aux calculs dans un cylindre périodique. Les différences dans la dynamique des deux cas sont mises en avant. Finalement les simulations sont confrontées à des expériences et un meilleur accord est observé entre simulation et expérience pour la géométrie toroïdale que pour la géométrie cylindrique. / A magnetohydrodynamic description is used to study magnetic fusion plasmas in two different configurations: tokamak and reversed field pinch. A Fourier pseudo-spectral method with a volume penalization technique are used to solve the system of equations. The penalization method is used to introduce Dirichlet boundary conditions and it al- lows to easily modify the consider geometry. The simulations of a tokamak configuration in a toroidal geometry show the spontaneous appearance of velocities. These velocities are dominated by their toroidal component if the system is little dissipative. It is also shown that the symmetry breaking of the cross section of the torus causes a toroidal angular momentum to develop. For the Reversed Field Pinch configuration we show the appearance of helical structures. The shape of these structures varies with the value of the transport coefficients and with the pinch ratio parameter of the imposed magnetic field. To complete the study, we compare the results of simulations obtained in toroidal and in periodic cylindrical geometries. The differences in the dynamics of these two cases are highlighted. Finally, simulations are compared to experimental data and a significant better agreement is observed between the simulation and the experiment for the toroidal geometry than for the cylindrical case.

The Sun, by the virtue of its proximity to Earth, serves as an excellent astrophysical laboratory for testing our theoretical ideas. The Sun displays a plethora of visually awe-inspiring phenomena including flares, prominences, sunspots, corona, CMEs and uncountable others. It is now known that it is the magnetic field of the Sun which governs all these and also the geomagnetic storms at the Earth, which owes its presence to the interaction between the geomagnetic field and the all-pervading Solar magnetic field in the interplanetary medium. Since the solar magnetic field affects the interplanetary space around the Earth in a profound manner, it is absolutely essential that we develop a comprehensive understanding of the generation and manifestation of magnetic fields of the Sun. This thesis aims at developing a state-of-the-art dynamo code SURYA1taking into account important results from helioseismology and magnetohydrodynamics. This dynamo code is then used to study various phenomenon associated with solar activity including evolution of solar parity, response to stochastic fluctuations, helicity of active regions and prediction of future solar cycles. Within last few years dynamo theorists seem to have reached a consensus on the basic characteristics of a solar dynamo model. The solar dynamo is now believed to be comprised of three basic processes: (i)The toroidal field is produced by stretching of poloidal field lines primarily inside the tachocline – the region of strong radial shear at the bottom of the convection zone. (ii) The toroidal field so formed rises to the surface due to magnetic buoyancy to form active regions. (iii) Poloidal field is generated at the surface due to decay of tilted active regions – an idea attributed to Babcock (1961) & Leighton (1969). The meridional circulation then carries the poloidal field produced near the surface to the tachocline. The profile of the solar differential rotation has now been mapped by helioseismology and so has been the poleward branch of meridional circulation near the surface. The model I describe in this thesis is a two-dimensional kinematic solar dynamo model in a full sphere. Our dynamo model Surya was developed over the years in stages by Prof. Arnab Rai Choudhuri, Dr. Mausumi Dikpati, Dr. Dibyendu Nandy and myself. We provide all the technical details of our model in Chap. 2 of this thesis. In this model we assume the equatorward branch of the meridional circulation (which hasn’t been observed yet), to penetrate slightly below the tachocline (Nandy & Choudhuri 2002, Science, 296, 1671). Such a meridional circulation plays an important role in suppressing the magnetic flux eruptions at high latitudes. The only non-linearity included in the model is the prescription of magnetic buoyancy. Our model is shown to reproduce various aspects of observational data, including the phase relation between sunspots and the weak, efficient. An important characteristic of our code is that it displays solar-like dipolar parity (anti-symmetric toroidal fields across equator) when certain reasonable conditions are satisfied, the most important condition being the requirement that the poloidal field should diffuse efficiently to get coupled across the equator. When the magnetic coupling between the hemispheres is enhanced by either increasing the diffusion or introducing an α ff distributed throughout the convection zone, we find that the solutions in the two hemispheres evolve together with a single period even when we make the meridional circulation or the α effect different in the two hemispheres. The effect of diffusive coupling in our model is investigated in Chap. 3. After having explored the regular behaviour of the solar cycle using the dynamo code we proceed to study the irregularities of the Solar cycle.We introduce stochastic fluctuations in the poloidal source term at the solar surface keeping the meridional circulation steady for all the numerical experiments. The dynamo displays oscillatory behaviour with variable cycle amplitudes in presence of fluctuations with amplitudes as large as 200%. We also find a statistically significant correlation between the strength of polar fields at the endofone cycle and the sunspot number of the next cycle. In contrast to this there exist a very poor correlation between the sunspot number of a cycle and the polar field formed at its end. This suggests that during the declining phase of the sunspot cycle poloidal field generation from decaying spots takes place via the Babcock-Leighton mechanism which involves randomness and destroys the correlation between sunspot number of a cycle and the polar at its end. In addition to this we also see that the time series of asymmetries in the sunspot activity follows the time series of asymmetries in the polar field strength with a lag of 5 years. We also compare our finding with available observational data. Although systematic measurements of the Sun’s polar magnetic field exist only from mid-1970s, other proxies can be used to infer the polar field at earlier times. The observational data indicate a strong correlation between the polar field at a sunspot minimum and the strength of the next cycle, although the strength of the cycle is not correlated well with the polar field produced at its end. We use these findings about the correlation of polar fields with sunspots to develop an elegant method for predicting future solar cycles. We feed observational data for polar fields during the minima of cycle n into our dynamo model and run the code till the next minima in order to simulate the sunspot number curve for cycle n+1. Our results fit the observed sunspot numbers of cycles 21-23 reasonably well and predict that cycle 24 will be about 30–35% weaker than cycle 23. We fit that the magnetic diffusivity in the model plays an important role in determining the magnetic memory of the Solar dynamo. For low diffusivity, the amplitude of a sunspot cycle appears to be a complex function of the history of the polar field of earlier cycles. Only if the magnetic diffusivity within the convection zone is assumed to be high (of order 1012cms−1), we are able to explain the correlation between the polar fiat a minimum and the next cycle. We give several independent arguments that the diffusivity must be of this order. In a dynamo model with diffusivity like this, the poloidal field generated at the mid-latitudes is advected toward the poles by the meridional circulation and simultaneously diffuses towards the tachocline, where the toroidal field for the next cycle is produced. The above ideas are put forward in Chap. 6. We next come to an important product of the dynamo process namely the magnetic helicity. It has been shown independently by many research groups that the mean value of the normalized current helicity αp= B (Δ×B)/B2in solar active regions is of the order of 10−8m−1, predominantly negative in the northern hemisphere, positive in the southern hemisphere. Choudhuri (2003, Sol. Phys., 215, 31)developed a model for production of the helicity of the required sign in a Babcock-Leighton Dynamo by wrapping of poloidal field lines around a fluxtube rising through the convection zone. In Chap. 7 we calculate helicities of solar active regions based on this idea. Rough estimates based on this idea compare favourably with the observed magnitude of helicity. We use our solar dynamo model to study how helicity varies with latitude and time. At the time of solar maximum, our theoretical model gives negative helicity in the northern hemisphere and positive helicity in the south, in accordance with observed hemispheric trends. However, we fit that during a short interval at the beginning of a cycle, helicities tend to be opposite of the preferred hemispheric trends. After calculating the sign and magnitude of helicity of the sunspots we worry about the distribution of helicity inside a sunspot. In Chap. 8 we model the penetration of a wrapped up background poloidal field into a toroidal magnetic flux tube rising through the solar convective zone. The rise of the straight, cylindrical flux tube is followed by numerically solving the induction equation in a comoving Lagrangian frame, while an external poloidal magnetic field is assumed to be radially advected onto the tube with a speed corresponding to the rise velocity. One prediction of our model is the existence of a ring of reverse current helicity on the periphery of active regions. On the other hand, the amplitude of the resulting twist depends sensitively on the assumed structure (ffvs. concentrated/intermittent) of the active region magnetic field right before its emergence, and on the assumed vertical profile of the poloidal field. Nevertheless, in the model with the most plausible choice of assumptions a mean twist comparable to the observational results. Our results indicate that the contribution of this mechanism to the twist can be quite find under favourable circumstances it can potentially account for most of the current helicity observed in active regions.

No description available.

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.