L’instabilité d’ADN mitochondrial (ADNmt) peut être quantitative avec la déplétion de l’ADNmt ou qualitative avec des délétions de l’ADNmt. Ces anomalies sont une des causes les plus commmunes des maladies mitochondriales. Un des gènes qui contrôle la stabilité et le maintien de l’ADNmt est POLG. Ce gène code pour la polymerase gamma mitochondriale. Chez l’homme, les mutations dans le gène POLG sont liées aux maladies mitochondriales telle que; l’insuffisance hépatique, le syndrome d’Alpers, le PEO ou Progressive External Ophtalmoplegia, la neuropathie sensorielle et l’ataxie. Des mutations dans le gène POLG sont aussi associées au syndrome de Parkinson. Aujourd’hui, il n’existe aucune thérapie pour ces maladies. Compte tenu de la conservation évolutive de la fonction mitochondriale de la levure à l’homme, nous avons utilisé deux organismes modèles, Saccharomyces cerevisiae et Caenorhabditis elegans, pour identifier des molecules chimiques capables de compenser l’instabilité de l’ADNmt liée à des mutations du gène POLG dans des fibroblastes d’un patient. Nous avons trouvé trois molécules candidates potentielles: MRS2, MRS3 et MRS4, à partir d’un criblage primaire chez la levure, en utilisant une chimiothèque d’environ 2000 molécules chimiques. MRS3 est la molécule candidate la plus efficace pour la stabilization d’ADNmt chez des mutants POLG de la levure, du champignon filamenteux, du nématode et sur des fibroblastes de patients. MRS3, ou clofilium tosylate (CLO), est un agent antiarrhytmique, médicament pour soigner les troubles du rythme cardiaque. Dans cette étude, nous avons aussi montré que deux autres antiarrhythmiques appartenant à la même classe que CLO avaient un effet positive chez un mutant POLG de C. elegans. En utilisant une approche de chemogénomique chez la levure, nous avons identifié Fis1, un acteur de la fission mitochondriale qui pourrait être impliqué dans la mode d’action de CLO. Fis1 est requise pour la viabilité cellulaire en concentration légèrement toxique de CLO et nécesaire pour la stabilization de l’ADNmt par CLO. L’ensemble de ces résultats ont montré que CLO pourrait être la première molécule chimique qui stimule la réplication de l’ADNmt et qui pourrait être développée pour le traitement des maladies liées à des mutations dans le gène POLG. Ces résultats ont aussi permis de mettre en évidence une nouvelle connexion entre replication de l’ADNmt et la fission mitochondriale. / The instability of mitochondrial DNA (mtDNA) in form of mtDNA depletion (quantitative instability) or large deletion (qualitative instability) is one of the most common cause of mitochondrial diseases.. One of the genes responsible for human mtDNA stability, POLG, is exploited in this study. POLG encodes the human mitochondrial polymerase gamma. In human, POLG mutations are a major cause of mitochondrial disorders including hepatic insufficiency; Alpers syndrome, progressive external ophthalmoplegia, sensory neuropathy and ataxia. They are also associated with Parkinsonism. Currently, there is no effective and disease-specific therapy for these diseases. Based on the conservation of mitochondrial function from yeast to human, we used Saccharomyces cerevisiae and Caenorhabditis elegans as first pass filters to identify chemical compounds that suppresses mtDNA instability in cultured fibroblasts of a POLG-deficient patient. We found three potential candidates, MRS2, MRS3 and MRS4, from a chemical screening of nearly 2000 compounds in yeast. MRS3 is the most efficacious in stabilizing mtDNA in yeast, filamentous fungi, worm and patient fibroblasts. This unsuspected compound, clofilium tosylate (CLO), belongs to a class of antiarrhythmic agents for cardiovascular disease. Two other antiarrhythmic agents (FDA-approved) sharing common pharmacological properties and chemical structure with CLO also show potential benefit for POLG deficiency in C. elegans. Using a chemogenomic approach in yeast, we also discovered that a mitochondrial fission actor Fis1 is implicated in the mechanism of action of CLO. Fis1 is important for cellular viability in a slightly toxic concentration of CLO and is required for the mtDNA stabilizing potency of CLO. Our findings provide evidence of the first mtDNA-stabilizing compound that may be an effective pharmacological alternative for the treatment of POLG-related diseases and uncover a new connection between the mitochondrial fission process and mtDNA replication. / Ketidakstabilan DNA mitokondria (mtDNA) dalam bentuk pengurangan kopi mtDNA di dalam sel (ketidakstabilan kuantitatif), atau pun dalam bentuk delesi pada sekuens mtDNA (ketidakstabilan kualitatif) merupakan salah satu penyebab penyakit mitokondria. Salah satu gen yang bertanggung jawab dalam menjamin kestabilan mtDNA adalah POLG. Gen POLG mengkode protein polimerase gamma pada manusia, yang mereplikasi dan mereparasi mtDNA di dalam mitokondria. Mutasi pada gen POLG dapat menyebabkan penyakit kelainan mitokondria pada manusia, seperti gagal ginjal, sindrom Alpers, Progressive External Ophtalmoplegia, neuropati sensorial, ataxia dan bisa dikaitkan dalam beberapa gejala Parkinsonisme. Saat ini, belum ada terapi obat yang dapat mengatasi penyakit – penyakit tersebut. Berdasarkan kesamaan evolutif dari ragi hingga manusia, pada studi ini kami menggunakan Saccharomyces cerevisiae dan Caenorhabditis elegans untuk mengidentifikasi molekul obat yang berpotensi mengatasi ketidakstabilan mtDNA dari fibroblas pasien manusia yang memiliki mutasi gen POLG. Kami mengidentifikasi tiga kandidat potensial, yakni MRS2, MRS3 dan MRS4 dari penapisan kurang lebih 2000 molekul obat dengan menggunakan ragi. MRS3 adalah kandidat yang paling berkhasiat dan mampu mengatasi ketidakstabilan mtDNA pada ragi, Podospora, cacing dan fibroblas manusia. MRS3 adalah alias bagi clofilium tosylate (CLO), sebuah molekul antiaritmia untuk penyakit kardiovaskuler. Pada studi ini, kami juga menguji aktifitas dua molekul antiaritmia lain yang tergabung dalam kelas yang sama dengan CLO, dan menemukan bahwa kedua molekul ini juga berpotensi mengatasi defisit POLG pada cacing C. elegans. Dengan menggunakan metode kemogenomik pada ragi, kami juga mengidentifikasi sebuah aktor prosesus pembelahan mitokondria, Fis1, yang berpotensi terlibat dalam mekanisme seluler CLO. Fis1 dibutuhkan untuk: (1) kelangsungan hidup ragi pada konsentrasi toksik CLO dan (2) efek CLO dalam menstabilkan mtDNA pada ragi. Keseluruhan studi ini membuktikan potensi CLO sebagai molekul penstabil mtDNA yang pertama, yang dapat dikembangkan sebagai salah satu alternatif terapi obat untuk penyakit – penyakit mitokondria terkait mutasi POLG. Melalui studi ini, juga diungkap adanya hubungan antara kestabilan mtDNA dan prosesus pembelahan mitokondria.

Yes / Fluorine substitution is an established tool in medicinal chemistry to favourably alter the molecular properties of a lead compound of interest. However, gaps still exist in the library of synthetic methods for accessing certain fluorine-substituted motifs. One such area is the fluoromethyl group, particularly when required in a fluoroalkylating capacity. The cold fluorination of methylene ditosylate is under evaluated in the literature, often proceeding with low yields or harsh conditions. This report describes a novel microwave method for the rapid nucleophilic fluorination of methylene ditosylate using inexpensive reagents in good isolated yield (65%).

No description available.

No / A new and convenient method for the acid-catalysed Michael addition reactions of alcohols, thiols and amines to methyl vinyl ketone has been developed using the ionic liquid ethyltri-n-butylphosphonium tosylate. The reaction conditions are mild and obviate the need for toxic and expensive Lewis acid catalysts, offering advantages over more commonly used systems.

Electroactive textile fibers are key components in smart and interactive textile applications. In previous research on textile base conductive fibers, viscose fibers were coated with poly (3,4-ethylenedioxythiophne) (PEDOT) using oxidative chemical vapor deposition (oCVD) technique[1]. Ferric chloride was used as oxidant and reaction conditions were optimized at which better electrical as well as mechanical properties of conductive viscose fibers could be achieved. In this thesis work, effect of new parameters such as pretreatment of viscose fibers with solvents, drying of oxidant treated viscose fibers at different time and temperature and comparison of two different oxidants have been tried. One new and important oxidant, ferric (III) p-toluene sulfonate or ferric (III) tosylate, used to prepare PEDOT coated viscose fibers and then compared with PEDOT coated viscose fibers prepared using oxidant ferric (III) chloride. Viscose fibers have been treated with two well know solvents, acetone and ethyl acetate before soaking in oxidant solution. Oxidant enriched fibers dried at different temperature for variable time prior to polymerization step. Knitted structures of conductive viscose fibers have been prepared. Hand washing of PEDOT coated viscose fibers with tap water and machine washing of knitted structures according to the international standard ISO EN-6330 have been performed and washing effects were investigated. Effects of all of the above mentioned variables on electromechanical properties of PEDOT coated viscose fibers were studied by using tensile testing, TGA analysis, FTIR spectra and conductivity measurements. Stretch sensing properties of knitted structures; before and after washing, were determined on cyclic tester. The purpose of this study is to enhance the properties of PEDOT-coated viscose fibers by controlling different parameters and to evaluate their usage as stretch sensors as well as to check the washability of PEDOT coated viscose fibers and knitted structures. Better electromechanical properties were achieved on new parameters and PEDOT coated viscose fibers were successfully utilized as stretch sensors. PEDOT coated viscose fibers could have potential to apply in areas such as, military textiles, medical textiles and sensors. / Program: Master programme in Textile Technology

In this thesis, we have tried to explain the regular and irregular(chaotic) dynamics of worm like micellar solutions on applying shear, through a detailed study of the equation of motion of a nematic order parameter tensor coupled to a hydrodynamic velocity field. We have assumed spatial variations only along one direction i.e. the gradient direction(1D model). The resulting phase diagram shows various interesting steady states or phases such as spatiotemporal chaos, temporal and spatiotemporal periodicities, and alignment of the director axis along the imposed flow field. The coupling of the orientational degrees of freedom of the order parameter with the hydrodynamic flow field holds the key to the appearance of dynamic shear bands in the system. We have solved numerically a set of coupled nonlinear equations to obtain the order parameter stress developed in the system; the magnitude of the order parameter tensor, the biaxiality parameter and the orientation of the director axis of the nemato gens under shear have also been studied in detail. To study the phase diagram obtained by time integration of the equation of motion mathematically, a stability analysis of the fixed point of motion for various parameter values has been performed so that the location of the chaotic-to-aligned phase boundary is verified. Also in the periodic region of the phase diagram, the stability of limit cycles is tested by analysing the fixed point of the corresponding Poincare map. Stability analysis of the periodic orbits leads to the observation that in the parameter space, there are regions of phase coexistence where chaotic or spatiotemporally intermittent behaviour coexists with periodic behaviour. When corrections in the imposed velocity field due to the order parameter stress were taken into account and the order parameter response was looked into at several points in the parameter space, the modified equations of motion were found to reproduce the earlier behaviour in all the different regimes if the value of a dimensionless viscosity parameter is taken to be such that the bare viscous stress overrides the order parameter stress. The phase boundaries are however different from the ones seen in the earlier model. However, for a choice of the viscosity parameter such that the order parameter stress and the bare viscous stress are comparable, we see two distinctly different attractors: a banded, periodic one that is common to both α1equalto 0, and not equal to 0 and a banded chaotic one for α1not equal to 0. Here, α1is a parameter that governs the nonlinearity in the stretching of the order parameter tensor along the direction of the applied shear. Quantitative analysis of the various chaotic attractors throws up not only positive Lyapunov exponents but also that the banded chaos is a “flip-flop” kind of chaos where the switching between two long-lived states of high and lows hear stress is chaotic, where as the behaviour in either of the two states is periodic, with either a single, isolated frequency or a bunch of harmonics. Also, the spatial correlation of the shear stress in the chaotic attractors is of much larger range than the temporal correlation, the latter being almost delta-function-like. On increasing the temperature of the system till it is above the isotropic–nematic transition temperature in the absence of shear, we find that under shear, similar attractors as those in the nematic case are observed, both for passive advection and for the full 1D hydrodynamics. This is an encouraging result since actual experiments are performed at a temperature for which the system is in the isotropic phase in the absence of shear. Thus for the 1D system, the parameter space has been explored quite extensively. Considering spatial variations only along the gradient axis of the system under shear is not enough since experiments have observed interesting behaviour in the vorticity plane in which Taylor velocity rolls were noted. Hence taking the system to 2D was necessary. Our numerical study of the 2D system under shear is incomplete because we came across computational difficulties. However, on shorter time scales we have seen a two-banded state with an oscillating interface and Taylor velocity rolls as well. The methodology used for the 2D study can also be used to reproduce the 1D results by the simple step of taking initial condition with no variation in the vorticity direction. This automatically ensures that no variation in the vorticity direction ever builds up because the equations of motion ensure that these variations in the system do not grow by themselves unless fed in at the start. Using this method, we were able to reproduce all the attractors found in the 1D calculation. Thus the 1D attractors have been observed using two different methods of calculation. Further work on the full 2D numerics needs to be done because we believe that spatiotemporally complex steady-state attractor s exist in the 2D system also for appropriate values of the parameters.

Soft condensed matter (SCM) systems are ubiquitous in nature. SCM systems contain mesoscopic structures in the size range 10 nm to 1 am that are held together by weak entropic forces. These materials are therefore easily perturbed by external fields such as shear, gravity and electric and magnetic fields and are novel systems for studying non-equilibrium phenomena. The elastic constants of these materials are ≈ 109 times smaller than conventional atomic fluids and hence it is possible to measure the viscoelastic response of these materials using commercial instruments such as rheometers. The relaxation time in SCM systems are of the order of milliseconds as compared to atomic systems where relaxation times are of the order of picoseconds. It is easy to study the effect of shear on SCM, as the shear rates attainable by commercial rheometers are of the order of the inverse of their relaxation times. The dynamics of SCM systems and their local rheological properties obtained using the method of probe diffusion can be quantified through dynamic light scattering experiments. The structure of SCM systems can be quantified using diffraction techniques such as small angle x-ray scattering. In this thesis we report experimental studies on the linear and nonlinear rheology and the dynamics of surfactant cetyltrimethylammonium tosylate (CTAT), which forms cylindrical wormlike micelles, studied using bulk rheology and dynamic light scattering (DLS) technique, respectively. We have also studied the phase behaviour of the ternary system formed by cetyltrimethylammonium 3-hydroxy-napthalene 2-carboxylate (CTAHN), sodium bromide (NaBr) and water using small angle x-ray scattering (SAXS). In Chapter 1, we discuss why SCM systems are suitable for studying non-equilibrium phenomena such as the effect of shear on the structure and dynamics of condensed matter. This is followed by a discussion on the chemical structure, phase behaviour and self assembling properties of the amphiphilic molecules in water. We then discuss the intermacromolecular forces such as van der Waals interaction, the screened Coulomb repulsion and hydrophobic and hydration forces. The systems that have been the subject of our experimental studies, viz. CTAT and CTAHN/NaBr/water have also been discussed in detail. This is followed by a theoretical background of linear and nonlinear rheology, dynamic light scattering and small angle x-ray scattering techniques. Next we describe the stress relaxation mechanisms in wormlike micelles. This is followed by a discussion on some standard techniques of nonlinear time series analysis, in particular the evaluation of the delay time L, the embedding dimension m, the correlation dimension ν and the Lyapunov exponent λ. We have also mentioned a few examples of experimental systems where chaos has been observed. We have also discussed in detail the various routes to chaos namely, the period-doubling route, the quasiperiodic route and the intermittency route. The concluding part of this chapter summarises the main results of the thesis. Chapter 2 discusses the experimental apparatus used in our studies. We have discussed the different components of the MCR-300 stress-controlled rheometer (Paar Physica, Germany). The rheo-small angle light scattering experiments and the direct visualisation experiments done using a home-made shear cell are also discussed. Next we describe the various experiments that can be done using a commercial rheometer. The frequency response and flow experiments have been discussed with some examples from our own work on entangled, cylindrical micelles. This is followed by a discussion on the various components of our dynamic light scattering (DLS) setup (Brookhaven Instruments, USA). Particle sizing of submicrometer colloidal spheres using our DLS setup has been discussed with an example of an angle-resolved DLS study of 0.05µm polystyrene colloids. Next we describe the various components of the SAXS setup (Hecus M. Braun, Austria). As an example application of SAXS we have quantified the structure of the lamellar phase formed by the surfactant CTAHN/water. We finally describe the sample preparation methods employed by us for the different experiments. Our nonlinear rheology experiments on viscoelastic gels of surfactant CTAT (cCT AT= 2wt%) in the presence of salt sodium chloride (NaCl) at various concentrations has been discussed in Chapter 3. We observe a plateau in the measured flow curve and this is attributed to a mechanical instability of the shear banding type. The slope of this plateau can be tuned by the addition of salt NaCl. This slope is due to a concentration difference between the shear bands arising from a Helfand-Fredrickson mechanism. This is confirmed by the presence of a “Butterfly” light scattering pattern in SALS experiments performed simultaneously with rheological measurements. We have carried out experiments at six different salt concentrations 10mM < cN aCl<1M, which yield plateau slopes (α) ranging from 0.07 < α < 0.4. We find that a minimum slope of 0.12, corresponding to a salt concentration of 25mM NaCl, is essential to see a “Butterfly” pattern indicating the onset of flow-concentration coupling at this α value. After this we turn our attention to stress/shear rate relaxation experiments. The remainder of this chapter is split in four parts. We show in Part-I that the routes to rheochaos in stress relaxation experiments is via Type-II intermittency. Interestingly in shear rate relaxation, the route is via Type-III intermittency. We also show that flow-concentration coupling is essential to see the route to rheochaos. This section also brings out the crucial role played by orientational ordering of the nematics during rheochaos using SALS measurements performed simultaneously with rheological measurements. In part-II, we study the spatio-temporal dynamics of the shear induced band en route to rheochaos. Our direct visualisation experiments show that the complex dynamics observed in stress/shear rate relaxation measurements during the route to rheochaos is a manifestation of the spatio-temporal dynamics of the high shear band. In part-III, we describe the results of our stress/shear rate relaxation measurements at a fixed shear rate/stress with temperature as the control parameter and thereby control the micellar length. We see the Type-II intermittency route to rheochaos in stress relaxation measurements and the Type-III intermittency route to rheochaos in shear rate relaxation measurements. We conclude this section by showing the results of linear rheology measurements carried out at different temperatures. We estimate the mean micellar length ¯L, reptation time τrepand the breaking time τbreak. We show that L¯ increases by ≈ 58%, as the sample goes through the route to rheochaos. In Part-I of this chapter we had only qualitatively discussed the correlations between the measured time series of stress and the VH scattered intensity during the Type-II intermittency route to rheochaos. In part-IV we have attempted to quantify the correlations between the two time series using the technique of linear and nonlinear Granger causality. We have also studied the phase space dynamics of the two time series using the technique of Cross Recurrence Plots. We show that there exists a causal feedback mechanism between the stress and the VH intensity with the latter having a stronger causal effect. We have also shown that the bivariate time series share similar phase space dynamics using the method of Cross Recurrence Plots. In chapter 4, we have studied the dynamics of wormlike micellar gels of surfactant CTAT using the DLS technique. We report an interesting result in the dynamics of these systems: concentration fluctuations in semidilute wormlike-micelle solutions of the cationic surfactant Cetyltrimethylammonium Tosylate (CTAT) at wavenumber q have a mean decay rate α qz, with z -̃1.8, for a wide range of surfactant concentrations just above the overlap value c∗. The process we are seeing is thus superdiffusive, like a L´evy flight, relaxing on a length scale L in a time of order less than L2 . The rheological behaviour of this system is highly non-Maxwellian and indicates that the micelle-recombination kinetics is diffusion-controlled (DC) (micelles recombine with their original partners). With added salt (100mM NaCl) the rheometric behaviour turns Maxwellian, indicating a crossover to a mean-field (MF) regime (micelles can recombine with any other micellar end). The concentration fluctuations, correspondingly, show normal diffusive behaviour. The stress relaxation time, moreover is about twenty times slower without salt than with 100mM NaCl. Towards the end of this chapter, we propose an explanation of these observations based on the idea that stress due to long-lived orientational order enhances concentration fluctuations in DC regime. In the previous chapter we had studied the dynamics of wormlike micellar gels of pure CTAT 2wt% and found superdiffusive relaxation of concentration fluctuations due to a nonlinear coupling of long-lived stress and orientational fluctuations to the con- centration. In chapter 5 we present results from dynamic light scattering experiments to quantify the diffusive motion of polystyrene (PS) colloids in the same system. This chapter is split in two parts. In Part-I, we discuss dynamics of PS particles of radius 115 nm and 60 nm in CTAT 2wt%. The radius of the colloidal spheres is comparable to the mesh size ξ = 80 nm of the wormlike micellar network and hence we are probing the network dynamics. We find that ∆r2(t) is wavevector independent at small and large lag times. However at intermediate times, we find an anomalous wavevector dependence which we believe arises from the rapid restructuring of the gel network. This anomalous wavevector dependence of ∆r2(t) disappears as the temperature is increased. In Part-II we discuss the dynamics of PS particles of radius 25 nm and 10 nm, smaller than ξ, in CTAT 1wt% & 2wt%. We once again find an anomalous wavevector dependence of ∆r2(t) at intermediate times for the 2wt% sample. Surprisingly, at large times the particle motion is not diffusive, rather ∆r2(t) saturates. We do not have a clear understanding of this as yet. Also for the 10 nm particle, the motion at small lag times is superdiffusive. The motion of these particles is probably influenced by the superdiffusion of concentration fluctuations observed in pure CTAT 2wt% system (chapter 4). In chapter 6, we report the observation of an intermediate mesh phase with rhom- bohedral symmetry, corresponding to the space group R¯3m, in the ternary system consisting of CTAHN/NaBr/water. It occurs at lower temperatures between a random mesh phase (LDα ) and a lamellar phase (Lα) on increasing the surfactant concentration φs. The micellar aggregates, both in the intermediate and random mesh phases, are found to be made up of a two-dimensional network of rod-like segments, with three rods meeting at each node. SAXS studies also show the presence of small angle peaks corresponding to ad−spacing of 25 nm. Freeze fracture electron microscopy results shows that this peak may correspond to the presence of nodule like structures with no long-range correlations. The thesis concludes with a summary of main results and a brief discussion of the scope for future work in Chapter 7.