Yip Kim-fung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 95-100). / Abstracts in English and Chinese. / Abstract --- p.I / Acknowledgement --- p.III / Table of Contents --- p.IV / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Motivation --- p.1 / Chapter 1.2 --- Objective --- p.6 / Chapter Chapter 2 --- Theory of Oscillators --- p.7 / Chapter 2.1 --- Oscillator Design --- p.7 / Chapter 2.1.1 --- Loop-Gain Method --- p.7 / Chapter 2.1.2 --- Negative Resistance-Conductance Method --- p.8 / Chapter 2.1.3 --- Crossed-Coupled Oscillator --- p.10 / Chapter Chapter 3 --- Noise Analysis --- p.15 / Chapter 3.1 --- Origin of Noise Sources --- p.16 / Chapter 3.1.1 --- Flicker Noise --- p.16 / Chapter 3.1.2 --- Thermal Noise --- p.17 / Chapter 3.1.3 --- Noise Model of Varactor --- p.18 / Chapter 3.1.4 --- Noise Model of Spiral Inductor --- p.19 / Chapter 3.2 --- Derivation of Resonator --- p.19 / Chapter 3.3 --- Phase Noise Model --- p.22 / Chapter 3.3.1 --- Leeson's Model --- p.23 / Chapter 3.3.2 --- Phase Noise Model defined by J. Cranincks and M Steyaert --- p.24 / Chapter 3.3.3 --- Non-linear Analysis of Phase Noise --- p.26 / Chapter 3.3.4 --- Flicker-Noise Upconversion Mechanism --- p.31 / Chapter 3.4 --- Phase Noise Reduction Techniques --- p.33 / Chapter 3.4.1 --- Conventional Tank Circuit Structure --- p.33 / Chapter 3.4.2 --- Enhanced Q tank circuit Structure --- p.35 / Chapter 3.4.3 --- Tank Circuit with parasitics --- p.37 / Chapter 3.4.4 --- Reduction of Up-converted Noise --- p.39 / Chapter Chapter 4 --- CMOS Technology and Device Modeling --- p.42 / Chapter 4.1 --- Device Modeling --- p.42 / Chapter 4.1.1 --- FET model --- p.42 / Chapter 4.1.2 --- Layout of Interdigitated FET --- p.46 / Chapter 4.1.3 --- Planar Inductor --- p.48 / Chapter 4.1.4 --- Circuit Model of Planar Inductor --- p.50 / Chapter 4.1.5 --- Inductor Layout Consideration --- p.54 / Chapter 4.1.6 --- CMOS RF Varactor --- p.55 / Chapter 4.1.7 --- Parasitics of PMOS-type varactor --- p.57 / Chapter Chapter 5 --- Design of Integrated CMOS VCOs --- p.59 / Chapter 5.1 --- 1.5GHz CMOS VCO Design --- p.59 / Chapter 5.1.1 --- Equivalent circuit model of differential LC VCO --- p.59 / Chapter 5.1.2 --- Reference Oscillator Circuit --- p.61 / Chapter 5.1.3 --- Proposed Oscillator Circuit --- p.62 / Chapter 5.1.4 --- Output buffer --- p.63 / Chapter 5.1.5 --- Biasing Circuitry --- p.64 / Chapter 5.2 --- Spiral Inductor Design --- p.65 / Chapter 5.3 --- Determination of W/L ratio of FET --- p.67 / Chapter 5.4 --- Varactor Design --- p.68 / Chapter 5.5 --- Layout (Cadence) --- p.69 / Chapter 5.6 --- Circuit Simulation (SpectreRF) --- p.74 / Chapter Chapter 6 --- Experimental Results and Discussion --- p.76 / Chapter 6.1 --- Measurement Setup --- p.76 / Chapter 6.2 --- Measurement results: Reference Oscillator Circuit --- p.81 / Chapter 6.2.1 --- Output Spectrum --- p.81 / Chapter 6.2.2 --- Phase Noise Performance --- p.82 / Chapter 6.2.3 --- Tuning Characteristic --- p.83 / Chapter 6.2.4 --- Microphotograph --- p.84 / Chapter 6.3 --- Measurement results: Proposed Oscillator Circuit --- p.85 / Chapter 6.3.1 --- Output Spectrum --- p.85 / Chapter 6.3.2 --- Phase Noise Performance --- p.86 / Chapter 6.3.3 --- Tuning Characteristic --- p.87 / Chapter 6.3.4 --- Microphotograph --- p.88 / Chapter 6.4 --- Comparison of Measured Results --- p.89 / Chapter 6.4.1 --- Phase Noise Performance --- p.89 / Chapter 6.4.2 --- Tuning Characteristic --- p.90 / Chapter Chapter 7 --- Conclusion and Future Work --- p.93 / Chapter 7.1 --- Conclusion --- p.93 / Chapter 7.2 --- Future Work --- p.94 / References --- p.95 / Author's Publication --- p.100 / Appendix A --- p.101 / Appendix B --- p.104 / Appendix C --- p.106

Le but initial de cette thèse était d’étudier les espaces de superlacets, version géométrique des espaces de supercordes en Physique. Le point de départ était alors d’étendre les résultats de classifications de l’article de Oleg Mokhov : Symplectic and Poisson structures on loop spaces of smooth manifolds, and integrable systems au cadre de la supergéométrie. Dans cet article l’auteur établit une classification des formes symplectiques locales homogènes d’ordre 0, 1 et 2 sur l’espace des lacets LM = C1(S1;M) à partir d’objets géométriques sur la variété différentiable M. Dans cette thèse, on remplace la variété M par une supervariété Mpjq et le cercle S1 par un supercercle S1jn et l’on étudie l’espace des morphismes de supervariétésMor(S1jn;Mpjq). Dans les deux premières parties, l’on définit les structures géométriques classiques et super des espaces de superlacets. Pour ce faire, l’on se restreint aux deux supercercles S1j1 et en s’inspirant des travaux sur LM, l’on détermine une structure de variété de Fréchet des espaces de superlacets SLM = Mor(S1j1;M). Puis l’on introduit la structure super qui nous a semblé la plus naturelle sur SLM en terme de faisceaux. Afin de pouvoir travailler en coordonnées, l’on introduit la structure super par un autre point de vue en considérant l’espace de superlacets SLM comme le foncteur de points SLM. De plus, en interprétant les calculs de Mokhov en terme de jets, ceci nous permet d’une part d’apporter une justification rigoureuse aux-dits calculs et d’autre part, d’obtenir une généralisation directe des méthodes de calculs en coordonnées ("à la physicienne"). Le troisième chapitre expose les résultats de classification obtenus. Comme dans le cas classique, on obtient un théorème de dépendance limitée de l’ordre des jets qui interviennent dans les formes d’ordre 0 et 1. Puis, on obtient une classification des formes d’ordre 0 au moyen de formes différentielles sur la supervariété Mpjq. Une classification des formes homogènes d’ordre 1 et 2 au moyen de métriques Riemaniennes et de connexions sur Mpjq. Enfin le quatrième chapitre est consacré à la généralisation des résultats d’un autre article de O. Mokhov : Complex homogeneous forms on loop spaces of smooth manifolds and their cohomology groups. De par la présence de la variable impaire, on précise tout d’abord la définition des formes homogènes locales sur SLM, puis on démontre que muni de la différentielle extérieure, l’espace des formes homogènes sur SLM d’ordre m 2 N donné définit un complexe. On calcule alors complètement les espaces de cohomologie pour les ordres m = 0 et 1, partiellement pour les ordres 2 et 3 et on explicite ainsi les formes symplectiques exactes obtenues au troisième chapitre. / The goal of the thesis was to study superloopspaces, the geometric version of superstrings in Physics, by extending the classification results contained in Oleg Mokov’s paper : Symplectic and Poisson structures on loop spaces of smooth manifolds, and integrable systems to the supergeometric setting. In it, lies the classification of local homogeneous symplectic forms of order 0, 1 and 2 on the loopspace LM = C1(S1;M) by means of geometric objects on the manifold M. In this thesis, the manifold M becomes a supermanifold Mpjq, the circle S1 becomes a supercircle S1jn and we consider the superloopspace as the space of morphisms of supermanifolds Mor(S1jn;Mpjq). In the two first chapters, we look at the classical and super geometric structures of the superloopspaces. To do this, we restrict ourselves to the two supercircles S1j1 and using the previous works on LM, we define a Fréchet manifold structure on the superloopspaces SLM = Mor(S1j1;M). Then we bring in what we consider as the most natural superstructure on SLM by means of sheaves. In order to work with coordinates, we adopt another point of view considering SLM as the functor of points SLM. Moreover, rewriting Mokhov results in terms of jets allows us to give a rigorous proof of those calculations and also to extend right away the methods of calculations in coordinates. The third chapter contains the new classification results we obtained. Similarly to the classical case, we first show that the order of the jets in the forms of order 0 and 1 is bounded. Then we give the complete classification of the symplectics forms of order 0 by means of differential forms on the manifold Mpjq and of homogeneous symplectics forms of order 1 and 2 using Riemannian metrics and connections on Mpjq. Finally, the fourth chapter is devoted to extending the cohomology results of an other Mokhov’s article : Complex homogeneous forms on loop spaces of smooth manifolds and their cohomology groups. We first discuss the dependance of the odd variable in the homogeneous forms on SLM, and show that with the exterior derivative, the space of homogeneous forms on SLM of a given order m 2 N is a complex. We then calculate the cohomological spaces, completely for the order m = 0 and 1, partially for the order 2 and 3 and we identify the exact forms amongst those of the third chapter.

Les protocoles de routage dans les réseaux peuvent être amenés à changer pour de nombreuses raisons : la détection d'un événement particulier, un changement de topologie planifié ou non, la mobilité des nœuds, l'obsolescence de version, etc. Ces changements ne pouvant être simultanément détectés ou pris en compte par tous les nœuds du réseau, il est nécessaire de considérer le cas où certains nœuds utilisent le protocole de routage initial, tandis que d'autres ont migré vers le nouveau protocole de routage. Les travaux de cette thèse portent sur le problème de boucles de routage susceptibles d'apparaître dans ce contexte, et qui dégradent considérablement les performances du réseau. Nous proposons des solutions d'ordonnancement des nœuds, dans le but de contrôler la migration afin d'éviter ces boucles. Premièrement, nous considérons le contexte des réseaux statiques et des protocoles centralisés avec pour cas particulier le changement de métriques dans le réseau. Nous proposons deux solutions d'évitement des boucles centralisées : SCH-m (amélioration mineure d'un protocole existant), et ACH (nouvelle contribution), basées sur l'identification des boucles de routage dans les composantes connexes que contient l'union des deux protocoles de routage. Nous accélérons la migration du réseau par une opération de fusion étape par étape des différentes transitions produites. Deuxièmement, nous évoluons vers les protocoles distribués en conservant le contexte statique du réseau, et considérons le cas particulier du retrait ou de la panne d'un nœud. Nous proposons également deux solutions : RTH-d (amélioration mineure d'un protocole existant) et DLF (nouvelle contribution traitant les boucles de taille 2) basées sur un échange de messages entre les nœuds tant pour la détection de la panne que pour la notification de la migration. Troisièmement, nous considérons le contexte de mobilité des nœuds, et étudions les performances de DLF-k (version améliorée de DLF qui prend en compte les boucles de taille inférieures ou égales à k, avec k >= 2) sur deux types d'applications : les applications avec un unique nœud mobile qui est la destination, et les applications avec un groupe de nœuds mobiles. / Routing protocols in networks may change for many reasons: detection of a particular event, planned or unplanned change of topology, mobility of nodes, version obsolescence, etc. As these changes can not be simultaneously detected or taken into account by all nodes of the network, it is necessary to consider the case where some nodes use the initial routing protocol, while others have migrated to the new routing protocol. The work of this thesis deals with the problem of routing loops that may appear in this context, and which considerably degrade the performance of the network. We propose node scheduling solutions to control migration to avoid these loops. First, we consider the context of static networks and centralized protocols with the particular case of changing metrics. We propose two centralized avoidance solutions: SCH-m (minor improvement of an existing heuristic), and ACH (new contribution), based on the identification of the routing loops in the strongly connected components contained in the union of the two routing protocols. We accelerate the migration of the network by a step-by-step merge operation of the different transitions produced. Second, we evolve towards the distributed protocols while preserving the static context of the network, and consider the particular case of the withdrawal or breakdown of a node. We also propose two solutions: RTH-d (minor improvement of an existing heuristic) and DLF (new contribution for loops of size 2) based on message exchange of nodes for both failure detection and for migration notification. Thirdly, we consider the context of nodes mobility, and study the performance of DLF- k (improved version of DLF which takes into account loops of size less than or equal to k, with k >= 2) on two types of applications: applications with a single mobile node that is the destination, and applications with a group of mobile nodes.

Digital communication systems invariably employ an underlying analog communication channel. At the transmitter, data is modulated to obtain an analog waveform which is input to the channel. At the receiver, the output of the channel needs to be mapped back into the discrete domain. To this effect, the continuous-time received waveform is sampled at instants chosen by the timing recovery block. Therefore, timing recovery is an essential component of digital communication systems. A widely used timing recovery method is based on a phase-locked loop (PLL), which updates its timing estimates based on a decision-directed device. Timing recovery performance is a strong function of the reliability of decisions, and hence, of the channel signal-to-noise ratio (SNR). Iteratively decodable error-control codes (ECCs) like turbo codes and LDPC codes allow operation at SNRs lower than ever before, thus exacerbating timing recovery. We propose iterative timing recovery, where the timing recovery block, the equalizer and the ECC decoder exchange information, giving the timing recovery block access to decisions that are much more reliable than the instantaneous ones. This provides significant SNR gains at a marginal complexity penalty over a conventional turbo equalizer where the equalizer and the ECC decoder exchange information. We also derive the Cramer-Rao bound, which is a lower bound on the estimation error variance of any timing estimator, and propose timing recovery methods that outperform the conventional PLL and achieve the Cramer-Rao bound in some cases. At low SNR, timing recovery suffers from cycle slips, where the receiver drops or adds one or more symbols, and consequently, almost always the ECC decoder fails to decode. Iterative timing recovery has the ability to corrects cycle slips. To reduce the number of iterations, we propose cycle slip detection and correction methods. With iterative timing recovery, the PLL with cycle slip detection and correction recovers most of the SNR loss of the conventional receiver that separates timing recovery and turbo equalization.

A Delay-Locked Loop (DLL) for the generation of multiple clock phases/delays is proposed. Several new techniques are used to help enhance the DLLs performance, specifically, to achieve wide lock range, short locking time, and reduced jitter. The DLL can be used for a variety of applications which require precise time intervals or phase shifts. The phase detector (PD), charge pump (CP), and voltage-controlled delay line (VCDL) are the three most important blocks in a DLL. In our research, we have proposed a novel structure which integrates the functionality of both the PD and CP. By using this structure, a fast switching speed can be achieved. Moreover, the combined PD and CP also lead to reduced chip area and better jitter performance. A novel phase detection algorithm is developed and implemented in the combined PD and CP structure. This algorithm also involves a start-control circuit to avoid locking failure or false lock to harmonics. With the help of this algorithm, the proposed DLL is able to achieve lock as long as the minimum VCDL delay is less than one reference clock cycle, which is the largest possible lock range that can be achieved by the DLL. The VCDL uses fully differential signaling to minimize jitter. The delay stage of the VCDL is built with a differential topology using symmetrical loads and replica-feedback biasing, which provides a low sensitivity to supply and substrate noise as well as a wide tuning range. In addition, a shift-averaging technique is used to improve the matching between delay stages and thus to equalize the delay of each individual stage.

The object of this research is to develop robust wire-line systems which demonstrate high performance while simultaneously consuming low power. The main focus of this work is the Clock and Data Recovery (CDR) system, which is the primary circuit of any modern wire-line transceiver. Different techniques starting from circuit-level to system-level have been investigated in this work to improve the performance of multi-gigabit CDRs. A 62 GHz bandwidth amplifier has been presented to address the need for a scalable amplifier for CDR needs. A new technique has been proposed to improve the radiation immunity of latches, to reduce the BER in CDRs occurring due to package radiations. An injection-lock based clock recovery method was investigated as an alternative to PLL based CDRs as they can be used for burst-mode wire-line communication. The investigation yielded the vulnerability of the method to jitter (false-locking and high jitter transfer), the attenuation of which is critical to commercial CDRs. A novel false-lock detector system has been proposed and demonstrated for the first time as a robust solution to the issue of false-locking of CDRs due to repetitive patterns. The implementation of the final CDR system required the use of an L-C tank VCO, the components of which are generic for all commercial CDRs. A new systematic layout technique for the VCO has been proposed and demonstrated in this work to substantially improve the layout area and the associated parasitics, approximately by 70 %. This new layout addresses a critical yet often neglected part of VCO design. Furthermore, a new concept has been proposed to optimize static dividers with respect to their power consumption and number of devices.

A frequency synthesizer plays a critical role in defining the performance of wireless systems in terms of measures such as operating frequency range, settling time, phase noise and spur performance, and area/power consumption. As the trend in mobile system design has changed from single-standard systems to multi-standard/multi-application systems, the role of frequency synthesizers has become even more important. As the most popular architecture, a phase-locked loop (PLL)-based frequency synthesizer has been researched over the last several decades; however, many unsolved problems related to the PLL-based synthesizer are still waiting for answers. This dissertation addresses key challenges related to fully integrated PLL-based frequency synthesizers, including the problem of large area consumption of passive components, the inherent reference-spur problem, and the problem of trade-offs between integer-N PLLs and fractional-N PLLs. In this dissertation, new techniques and architectures are presented and developed to address those challenges. First, a low-phase-noise ring oscillator and a capacitor multiplier with a high-multiplication factor efficiently minimize the silicon area of sub-components, and a compact programmable delay-locked loop (DLL)-based frequency multiplier is developed to replace the PLL-based frequency synthesizer. Second, the charge-distribution mechanism for suppressing reference spurs is theoretically analyzed, and an edge interpolation technique for implementing the mechanism is developed. Finally, the concept and the architecture of sub-integer-N PLL is proposed and implemented to remove trade-offs between conventional integer-N PLLs and fractional-N PLLs.

Traditional topics such as physics, chemistry and mathematics have immensely changed the world in the twentieth century, but the twenty-first century seems to be that of soft condensed matter physics, which has already shown its tremendous possibilities to influence the everyday human life through its technological manifestations such as biotechnology and soft nano technology. Unlike the traditional topics, soft condensed matter physics has an interdisciplinary nature. It studies systems that usually come under chemistry or biology, using the methods of physics and mathematics and hence, transcends the frontiers between the subjects. Soft matter may be classified into three main classes; colloidal dispersions, polymers and polymer melts and liquid crystals. Study of single polymer chains is a fascinating topic that provides insights to understand many processes occurring in biological systems. Here, we present analytical studies of a few such processes, involving single polymer chains. In fact, there are a number of biological processes, which involve the dynamics of a single polymer chain. Due to the importance of Brownian motion at the mesoscopic level, soft matter systems are always studied using the analytical as well as computational methods of statistical mechanics. The statistical mechanics of polymers has been developed into a fascinating topic due to the contributions from the theory of random walks and path integrals. The dynamical behavior of many-particle systems has been described traditionally by the so-called rate theories. Here, we use these classical approaches to study a few biological processes that involve single polymer chains. The kind of processes that we have investigated may be categorized into two, namely the processes that leads to conformational changes in a chain molecule and the processes involving spatial translocation of a polymer. In the first category, we have considered the dynamics of semiflexible polymer loops. Loop formation of chain molecules has a key role in biological processes like DNA replication, gene regulation and protein folding. Hence, the dynamics of a polymer closing to form a loop as well as opening of the loop are topics of considerable theoretical/experimental interest. For closing, results are available in the completely flexible limit. Wilemski and Fixman, (J. Chem. Phys.60, 878 (1974)) have studied the closing and opening reactions in a single flexible polymer chain and using their approach Doi found the closing time to vary with the length of the chain as L2 . Szabo, Schul-ten, and Schulten, (J. Chem. Phys. 72, 4350 (1980)) have used mean first passage time approach and they find that the closure time vary as L3/2. Both approaches have been compared with simulations (Pastor et.al, J. Chem. Phys., 105, 3878 (1996), Srinivas et. al,116,7276 (2002)). In the case of semiflexible chains, studies are fewer in comparison. However, real polymers such as DNA, RNA or proteins are not flexible and therefore, it is important to incorporate the intrinsic stiffness of the chain into account. In the worm-like chain model, the chain is described as a continuous, inextensible and differentiable space curve represented by the position vector r(s), where s is the arc length. Inextensibility of the chain requires that the tangent vector, u(s) = ∂r(s)/∂s, at any point on the curve must have unit magnitude, i.e, |u(s)| = 1. But incorporating this constraint has been a difficult problem in dealing with semiflexible polymers. Yamakawa and Stockmayer (J. Chem. Phys., 57, 2843 (1972)) and Shimada and Yamakawa (Macromolecules, 17, 689 (1984)) have calculated ring closure probabilities for worm-like chains and helical worm-like chains. Cherayil and Dua (J. Chem. Phys., 116, 399 (2002)) have calculated closure time for a semiflexible chain using the approximate model for semiflexible chains by Har-nau, Winkler and Reineker (J. Chem. Phys., 101, 8119 (1994)) and find that the closure time ~ Lν where ν is in the range 2.2 to 2.4. Physically, one expects that the closing time should decrease exponentially with length in the very short chain limit and then increase with length for longer chains. Hence, the closing time has a minimum at an intermediate length. The reason for this behavior is that, for short chains, the bending energy contributes significantly to the activation energy for the process. The activation energy ~ const./L and hence, the closing time τ ~ exp(const./L). For longer chains, the free energy barrier for closing is due to the configurational entropy and hence, τ obeys a power law. Recently, Jun et. al (Europhys. Lett., 64, 420 (2003)) have followed an approximate one dimensional Kramers approach to reproduce this behavior and obtained the minimum at a length Lmin = 3.4lp, where lp is the persistence length of the chain. Monte Carlo simulations by Chen et.al (Europhys. Lett., 65, 407 (2004)) lead Lmin = 2.85lp. We investigate (K. P. Santo and K. L. Sebastian, Phys. Rev. E, 73, 031923, (2006)) in detail the problem of loop opening for semiflexible polymers. The inextensibility constraint is incorporated rigorously by setting u(s) to be a unit vector in the angular direction (θ, φ) and the conformations of the polymer are then represented by Brownian motion over a unit sphere in the tangent vector space. We use the worm-like chain model, which takes into account the bending rigidity of the polymer. The bending energy can then be given in terms of the angle coordinates θ and φ. For the dynamics, we make use of a semiclassical approach, which is based on expanding the bending energy about a minimum energy path. For the sake of simplicity, we take the great circle on the unit sphere to be the minimum energy configuration of the loop and expand the bending energy up to second order in terms of fluctuations about this configuration. We find that, this is a very good approximation in the large stiffness limit, as this approach leads to a minimum energy value, which is very close to the exact calculations. The loop is unstable, unless the ends are bound to each other with a potential. Once the two ends have been brought together, they can separate from each other in any of the three directions in space. Considering the ring to be in the XY plane with the ends meeting in the Y-axis, we find that the separation in the X and Z directions are unstable as motion in these directions lead to decrease in bending energy. But the motion in the other direction, that is, the Y direction leads to increase in energy and is stable. Therefore, we choose the potential to be of Morse type in the X-direction and stable harmonic ones in the other two directions. With this, the potential energy surface for opening can be found and the rate of opening can be calculated using classical Transition State Theory. The effects of friction on the rate can also be incorporated using the standard coupling to a bath of harmonic oscillators . We find that for short chains, the rate is strongly length dependent and is well-described by the equation Aexp(B/x)/xν, with A and B constants, x = L/lp, L the length of the chain, lp the persistence length and ν ~ 1.2. However, for long chains, the rate is found to obey a power law. But in view of the fact that our approximations, while sensible for short semiflexible chains, are not expected to be valid for long flexible chains and therefore, this result is not expected to be correct. We also present results for the seemingly more biologically important reverse process, the closing of a semiflexible polymer, thus presenting a rather complete theory of dynamics of semiflexible polymer loops. In this work, we give a detailed multidimensional analysis of the closing dynamics of semiflexible chains by making use of the approximation scheme developed in the previous study of loop opening. We use the formalism of Wilemski and Fixman for the diffusion-controlled intra-chain reactions of polymers and their "closure" approximation for an arbitrary sink function. In this procedure, the closing time is expressed in terms of a sink-sink correlation function. We calculate this sink-sink correlation function through a normal mode analysis on the chain. The closing times, τclose for different lengths of the chain are then obtained. We find that τclose(L) ~ L4.5W(L), where W(L) was found to be described by B'exp(A'/L) with A' and B' constants. τclose(L) is found to have a minimum at Lmin = 2.4lp, which is to be compared with the values obtained through a one dimensional analysis (Europhys. Lett., 64, 420 (2003)) and simulations (Europhys. Lett., 65, 407 (2004)). We thus present a multidimensional analysis that give results that are physically expected. There does not seem to be any previous analysis which leads to these results shown through one-dimensional studies and simulations. In the category of translocation problems, we consider DNA packaging in viruses. DNA Packaging into the viral capsid is an essential step in any kind of viral infection. The mechanism of packaging in bacteriophage φ — 29 has recently been studied (Simpson et. al, Nature (London), 408, 745 (2000)). The study revealed the structure of the molecular motor that packages the DNA. In another experimental study, Smith et. Al (Nature (London), 408, 745 (2001)) have investigated the effect of applied external force on the packaging. Motivated by this study, we suggest (K. P. Santo and K. L. Sebastian, Phys. Rev. E, 65, 052902 (2002)) a simple model to explain the kinetics of packaging of DNA the external force, which tries to prevent it. The model suggests a Butler-Volmer kind of dependence of the rate of packaging on the pulling force. We find that our model explains the experimental data very well. Another very interesting situation that arises in biological contexts is the translocation of a polymer across a membrane through a pore. The uptake of DNA into the cell nucleus and the translocation of cytosolic protein into endoplasmic reticulum are examples. There have been two main classes of polymer translocation problems; translocation in presence of a field or driven by a molecular motor and the translocation assisted by the adsorption of molecules onto the chain in the region into which it is translocated. While the first class of problems is reasonably well understood, for the second class of problems a complete understanding still does not exist in the literature. The existing understanding of this kind of polymer translocation is mainly due to Simon, Peskin and Oster (Proc. Natl. Accad. Sci. USA, 89, 3770 (1992)), who describe the translocation as kind of biased Brownian motion, which is known as the Brownian Ratchet. But Brownian Ratchet is an idealization and can only be realized in certain limits and therefore, it does not account for the detailed dynamics of polymer and the binding particles. We present a simple statistical description of the problem. We find that in the regime where number of binding particles are larger than the number of adsorption sites on the chain, the translocation proceeds as if it is driven by a constant force and hence, seems to be governed by a mechanism similar to the kink mechanism (K. L. Sebastian and Alok. K. R. Paul, Phys. Rev. E, 62, 927 (2000), K. L. Sebastian, 61, 3245 (2000)) that has been suggested in the case translocation in presence of an external field. In the other regime, where the number of binding particles are less than the number of binding sites on the chain, the translocation was found to be predominantly diffusive.

Heart failure (HF) affects an estimated 5.8 million Americans, accounting for near 250,000 deaths each year. With shortages in available donor hearts, mechanical circulatory support (MCS) has emerged as a life-saving treatment for advanced stage HF. With growth in MCS use, a clinical and developmental need has emerged for a standard characterization and evaluation platform that may be utilized for inter-device comparison and system training. The goal of this research was to harness SynCardia's total artificial heart (TAH) to meet this need. We first sought to characterize the TAH in modern physiological terms - i.e. hemodynamics and pressure-volume loops. We then developed a model of HF using the TAH and mock circulatory system operating in a reduced output mode. We demonstrated that MCS devices could be incorporated and evaluated within the HF model. Finally, we characterized the operational envelope of SynCardia's Freedom (portable), Driver operating against varying loading conditions. Our results describe the hemodynamic envelope of the TAH. Uniquely, the TAH was found not to operate with time-varying elastance, to be insensitive to variations in afterload up to at least 135 mmHg mean aortic pressure, and exhibit Starling-like behavior. After transitioning the setup to mimic heart failure conditions, left atrial pressure and left ventricular pressure were noted to be elevated, aortic flow was reduced, sensitivity to afterload was increased, and Starling-like behavior was blunted, consistent with human heart failure. The system was then configured to allow ready addition of ventricular assist devices, which upon placement in the flow circuit resulted in restoration of hemodynamics to normal. Lastly, we demonstrated that the Freedom Driver is capable of overcoming systolic pressures of 200 mmHg as an upper driving limit. Understanding the physiology and hemodynamics of MCS devices is vital for proper use, future device development, and operator training. Characterization of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared to the human heart. The use of the system as a heart failure model has the potential to serve as a valuable research and teaching tool to foster safe MCS device use.

Le récepteur de l'acide rétinoïque RAR est une protéine de la superfamille des récepteurs nucléaires liant le ligand acide rétinoïque (AR). En présence de son ligand, RAR induit la transcription de ses gènes cibles alors qu'en son absence la transcription est inhibée. Le mécanisme de régulation de RAR est altéré dans les lignées cellulaires humaines de carcinome mammaire dû à une baisse de capacité de synthèse de l'AR. Aussi, l'expression des microARN (miR) est perturbée dans le cancer du sein et un grand nombre de gènes ont été identifiés, après une analyse in-silico, comme des cibles prédites des miRs. Ces derniers peuvent être régulés pas des facteurs de transcription et ils sont capables d'inhiber la prolifération cellulaire et d'induire l'apoptose via la régulation de leurs cibles. Ainsi, les miRs peuvent jouer un rôle dans le mécanisme de régulation de RAR et être impliqués dans des boucles de régulation avec ce récepteur. Dans le cadre de ce travail, nous décrivons une approche développée pour prédire et caractériser des circuits de régulation au niveau transcriptionnel et post-transcriptionnel dans le cancer du sein. Nous nous sommes intéressés aux boucles de régulation de type feed-forward où RAR régule un miR et en commun ils régulent un ensemble de gènes codants pour des protéines dans les cellules tumorales mammaires MCF7 et SKBR3. Ces circuits ont été construits en combinant des données de ChIP-chip de RAR et des données de micro-puces d'ADN tout en utilisant des outils in-silico de prédiction des gènes cibles de miRs. Afin de proposer le modèle approprié de régulation, une analyse in-silico des éléments de réponse de l'AR (RARE) dans les promoteurs des miRs est réalisée. Cette étape permet de prédire si la régulation par RAR est directe ou indirecte. Les boucles ainsi prédites sont filtrées en se basant sur des données d'expression de miR existantes dans des bases de données et dans différentes lignées cellulaires, en vue d'éliminer les faux positifs. De plus, seuls les circuits pertinents sur le plan biologique et trouvés enrichis dans Gene Ontology sont retenus. Nous proposons également d'inférer l'activité des miRs afin d'orienter leur régulation par RAR. L'approche a réussi à identifier des boucles validées expérimentalement. Plusieurs circuits de régulation prédits semblent être impliqués dans divers aspects du développement de l'organisme, de la prolifération et de la différenciation cellulaire. De plus, nous avons pu valider que let-7a peut être induit par l'AR dans les MCF7. / The retinoic acid receptor (RAR) is a type of nuclear receptor that is activated by the ligand retinoic acid (RA). In the presence of ligand, RAR induces the transcription of its targets whereas in the absence of ligand the transcription is blocked. The mechanism of regulation of RAR is altered in breast cancer cell lines due to a reduced capacity to synthesize RA. Also aberrant patterns of microRNA (miR) expression have been reported in human breast cancer and a number of genes involved in breast cancer progression have been identified by in-silico analysis to be targets of miRs. The miRs could be controlled by transcription factors and via the regulation of their mRNA targets, the miRs could promote apoptosis and even inhibit cell proliferation. Hence, the miRs may play a role in the mechanism of regulation of RAR and could be involved in regulatory loops with this receptor. In this work, we describe an approach developed for the prediction and characterization of mixed transcriptional and post-transcriptional regulatory circuits in breast cancer. We concentrated in particular on feed-forward loops, in which RAR regulates a miR, and together with it, a set of joint target protein coding genes in human breast cancer cell lines MCF7 and SKBR3. These loops are constructed by combining ChIP-chip datasets of RAR with datasets of DNA microarrays and by using miR target prediction tools. In order to predict the appropriate model of regulation, in-silico analysis was performed to look for retinoic acid response element (RARE) in miR promoter. This step could identify if the regulation by RAR is direct or indirect. The regulatory loops will be then filtered, in order to reduce the number of false positive, based on databases designed to represent human miR expression profiles in different tissues or cell types. Moreover, only biologically relevant circuits enriched in Gene Ontology were retained. Also, we propose to infer miR activity in order to detect their regulation by RAR. This approach was able to find some existing experimental data. Several regulatory circuits seem to be involved in various aspects of organism development, proliferation and cell differentiation. Furthermore, we were able to validate the induction of let-7a by RA in MCF7 cells.