The establishment of two novel bovine cell lines by transfection with the putative transforming region of bovine adenovirus type 3

Human adenoviruses (Ads), members of the family adenoviridae, are medium-sized DNA viruses which have been used as valuable research tools for the study of RNA processing, oncogenic transformation, and for the development of viral vectors for use in gene delivery and immunization technology. The left 12% of the linear Ad genollle codes for products which are necessary for the efficient replication of the virus, as well as being responsible for the forlllation of tumors in animallllodels. The establishlllent of the 293 cell line, by immortalization of human embryonic kidney cells with th~ E1 region of Ad type S (AdS), has facilitated extensive manipulation of the Ads and the development of recombinant Ad vectors. The study of bovine adenoviruses (BAVs), which cause mild respiratory and gastrointestinal infections in cattle has, on the other hand, been limited primarily to that of infectivity, immunology and clinicallllanifestations. As a result, any potential as gene delivery vehicles has not yet been realized. Continued research into the molecular biolo~gy of BAVs and the development of recolllbinant vectors would benefit from the development of a cell line analogous to that of the 293 cells. In an attelllpt to establish such a cell line, the recombinant plaslllid pKC-neo was constructed, containing the left 0-19.7% of the BAV type 3 (BAV3) genome, and the selectable marker for resistance to the aminoglycoside G418, a neomycin derivative. The plasmid construct was then used to transfect both the Madin-Darby bovine kidney (MDBK) -iicell line and primary bovine lung cells, after which G418-resistant foci were selected for analysis. Two cell lines, E61 (MDBK) and E24 (primary lung), were subsequently selected and analysed for DNA content, revealing the presence of the pKC-neo sequences in their respective genomes. In addition, BAV3 RNA transcripts were detected in the E61 cells. Although the presence of E1 products has yet to be confirmed in both cell lines, the E24 cells exhibit a phenotype characteristic of partial transformation by E1. The apparent immortalization of the primary lung cells will permit exploitation of their ability to take up exogenous DNA at high efficiency.

Phonon spectra and temperature variation of thermodynamic properties of fcc metals via Finnis-Sinclair type many body potentials: Sutton-Chen and improved Sutton-Chen models

Volume(density)-independent pair-potentials cannot describe metallic cohesion adequately as the presence of the free electron gas renders the total energy strongly dependent on the electron density. The embedded atom method (EAM) addresses this issue by replacing part of the total energy with an explicitly density-dependent term called the embedding function. Finnis and Sinclair proposed a model where the embedding function is taken to be proportional to the square root of the electron density. Models of this type are known as Finnis-Sinclair many body potentials. In this work we study a particular parametrization of the Finnis-Sinclair type potential, called the "Sutton-Chen" model, and a later version, called the "Quantum Sutton-Chen" model, to study the phonon spectra and the temperature variation thermodynamic properties of fcc metals. Both models give poor results for thermal expansion, which can be traced to rapid softening of transverse phonon frequencies with increasing lattice parameter. We identify the power law decay of the electron density with distance assumed by the model as the main cause of this behaviour and show that an exponentially decaying form of charge density improves the results significantly. Results for Sutton-Chen and our improved version of Sutton-Chen models are compared for four fcc metals: Cu, Ag, Au and Pt. The calculated properties are the phonon spectra, thermal expansion coefficient, isobaric heat capacity, adiabatic and isothermal bulk moduli, atomic root-mean-square displacement and Gr\"{u}neisen parameter. For the sake of comparison we have also considered two other models where the distance-dependence of the charge density is an exponential multiplied by polynomials. None of these models exhibits the instability against thermal expansion (premature melting) as shown by the Sutton-Chen model. We also present results obtained via pure pair potential models, in order to identify advantages and disadvantages of methods used to obtain the parameters of these potentials.

Impact of type of drug insurance on adherence, persistence and costs of antidepressant drugs : a Quebec population-based study

Contexte: À date, il existe peu de données sur l’adhésion, la persistance et les coûts associés aux antidépresseurs selon le type d’assurance médicament (privé ou public). Objectif: Comparer selon le régime d’assurance médicament (privé ou public), l'adhésion, la persistance et les coûts des antidépresseurs. Méthodes de recherche: Une étude de cohorte appariée a été réalisée en utilisant des bases de données du Québec. Sujets: Nous avons sélectionné 194 patients assurés par un régime privé et 1923 patients assurés par le régime public de la Régie de l’assurance maladie du Québec (RAMQ) (18-64 ans) qui ont rempli au moins une ordonnance pour un antidépresseur entre décembre 2007 et septembre 2009. Mesures: L’adhésion, mesurée sur une période d’un an, a été estimée en utilisant le proportion of prescribed days covered (PPDC). Un modèle de régression linéaire a été utilisé afin d’estimer la différence moyenne en PPDC entre les patients assurés par un régime privé et ceux assurés par le régime public de la RAMQ. La persistance a été comparé entre ces deux groupes avec un modèle de régression de survie Cox, et le coût mensuel d'antidépresseurs ($ CAN) a été comparé entre ces deux groupes en utilisant un modèle de régression linéaire. Résultats: Le PPDC parmi les patients assurés par un régime privé était de 86,4% (intervalle de confiance (IC) 95%: 83,3%-89,5%) versus 81,3% (IC 95%: 80,1%-82,5%) pour les patients assurés par le régime public de la RAMQ, pour une différence moyenne ajustée de 6,7% (IC 95%: 3,0%-10,4%). La persistance après un an parmi les patients assurés par un régime privé était de 49,5% versus 18,9% pour les patients assurés par le régime public de la RAMQ (p <0,001), et le rapport de risque ajusté était de 0,48 (IC 95%: 0,30-0,76). Comparativement aux patients assurés par le régime public de la RAMQ, les patients ayant une assurance privée ont payé 14,94 $ CAD (95% CI: $12,30-$17,58) de plus par mois en moyenne pour leurs antidépresseurs. Conclusion: Les patients assurés par un régime privé avaient une meilleure adhésion, persistance, mais avaient aussi un plus haut coût pour leurs antidépresseurs que ceux assurés par le régime public de la RAMQ. Cette différence de coûts peut être due aux différentes exigences de paiement en pharmacie entre les deux régimes ainsi qu’aux limites des honoraires des pharmaciens imposés par le régime public.

Genetic studies on the role of type IA DNA topoisomerases in DNA metabolism and genome maintenance in Escherichia coli

Le surenroulement de l’ADN est important pour tous les processus cellulaires qui requièrent la séparation des brins de l’ADN. Il est régulé par l’activité enzymatique des topoisomérases. La gyrase (gyrA et gyrB) utilise l’ATP pour introduire des supertours négatifs dans l’ADN, alors que la topoisomérase I (topA) et la topoisomérase IV (parC et parE) les éliminent. Les cellules déficientes pour la topoisomérase I sont viables si elles ont des mutations compensatoires dans un des gènes codant pour une sous-unité de la gyrase. Ces mutations réduisent le niveau de surenroulement négatif du chromosome et permettent la croissance bactérienne. Une de ces mutations engendre la production d'une gyrase thermosensible. L’activité de surenroulement de la gyrase en absence de la topoisomérase I cause l’accumulation d’ADN hyper-surenroulé négativement à cause de la formation de R-loops. La surproduction de la RNase HI (rnhA), une enzyme qui dégrade l’ARN des R-loops, permet de prévenir l’accumulation d’un excès de surenroulement négatif. En absence de RNase HI, des R-loops sont aussi formés et peuvent être utilisés pour déclencher la réplication de l’ADN indépendamment du système normal oriC/DnaA, un phénomène connu sous le nom de « constitutive stable DNA replication » (cSDR). Pour mieux comprendre le lien entre la formation de R-loops et l’excès de surenroulement négatif, nous avons construit un mutant conditionnel topA rnhA gyrB(Ts) avec l’expression inductible de la RNase HI à partir d’un plasmide. Nous avons trouvé que l’ADN des cellules de ce mutant était excessivement relâché au lieu d'être hypersurenroulé négativement en conditions de pénurie de RNase HI. La relaxation de l’ADN a été montrée comme étant indépendante de l'activité de la topoisomérase IV. Les cellules du triple mutant topA rnhA gyrB(Ts) forment de très longs filaments remplis d’ADN, montrant ainsi un défaut de ségrégation des chromosomes. La surproduction de la topoisomérase III (topB), une enzyme qui peut effectuer la décaténation de l’ADN, a corrigé les problèmes de ségrégation sans toutefois restaurer le niveau de surenroulement de l’ADN. Nous avons constaté que des extraits protéiques du mutant topA rnhA gyrB(Ts) pouvaient inhiber l’activité de surenroulement négatif de la gyrase dans des extraits d’une souche sauvage, suggérant ainsi que la pénurie de RNase HI avait déclenché une réponse cellulaire d’inhibition de cette activité de la gyrase. De plus, des expériences in vivo et in vitro ont montré qu’en absence de RNase HI, l’activité ATP-dépendante de surenroulement négatif de la gyrase était inhibée, alors que l’activité ATP-indépendante de cette enzyme demeurait intacte. Des suppresseurs extragéniques du défaut de croissance du triple mutant topA rnhA gyrB(Ts) qui corrigent également les problèmes de surenroulement et de ségrégation des chromosomes ont pour la plupart été cartographiés dans des gènes impliqués dans la réplication de l’ADN, le métabolisme des R-loops, ou la formation de fimbriae. La deuxième partie de ce projet avait pour but de comprendre les rôles des topoisomérases de type IA (topoisomérase I et topoisomérase III) dans la ségrégation et la stabilité du génome de Escherichia coli. Pour étudier ces rôles, nous avons utilisé des approches de génétique combinées avec la cytométrie en flux, l’analyse de type Western blot et la microscopie. Nous avons constaté que le phénotype Par- et les défauts de ségrégation des chromosomes d’un mutant gyrB(Ts) avaient été corrigés en inactivant topA, mais uniquement en présence du gène topB. En outre, nous avons démontré que la surproduction de la topoisomérase III pouvait corriger le phénotype Par- du mutant gyrB(Ts) sans toutefois corriger les défauts de croissance de ce dernier. La surproduction de topoisomérase IV, enzyme responsable de la décaténation des chromosomes chez E. coli, ne pouvait pas remplacer la topoisomérase III. Nos résultats suggèrent que les topoisomérases de type IA jouent un rôle important dans la ségrégation des chromosomes lorsque la gyrase est inefficace. Pour étudier le rôle des topoisomérases de type IA dans la stabilité du génome, la troisième partie du projet, nous avons utilisé des approches génétiques combinées avec des tests de « spot » et la microscopie. Nous avons constaté que les cellules déficientes en topoisomérase I avaient des défauts de ségrégation de chromosomes et de croissance liés à un excès de surenroulement négatif, et que ces défauts pouvaient être corrigés en inactivant recQ, recA ou par la surproduction de la topoisomérase III. Le suppresseur extragénique oriC15::aph isolé dans la première partie du projet pouvait également corriger ces problèmes. Les cellules déficientes en topoisomérases de type IA formaient des très longs filaments remplis d’ADN d’apparence diffuse et réparti inégalement dans la cellule. Ces phénotypes pouvaient être partiellement corrigés par la surproduction de la RNase HI ou en inactivant recA, ou encore par des suppresseurs isolés dans la première partie du projet et impliques dans le cSDR (dnaT18::aph et rne59::aph). Donc, dans E. coli, les topoisomérases de type IA jouent un rôle dans la stabilité du génome en inhibant la réplication inappropriée à partir de oriC et de R-loops, et en empêchant les défauts de ségrégation liés à la recombinaison RecA-dépendante, par leur action avec RecQ. Les travaux rapportés ici révèlent que la réplication inappropriée et dérégulée est une source majeure de l’instabilité génomique. Empêcher la réplication inappropriée permet la ségrégation des chromosomes et le maintien d’un génome stable. La RNase HI et les topoisomérases de type IA jouent un rôle majeur dans la prévention de la réplication inappropriée. La RNase HI réalise cette tâche en modulant l’activité de surenroulement ATP-dependante de la gyrase, et en empêchant la réplication à partir des R-loops. Les topoisomérases de type IA assurent le maintien de la stabilité du génome en empêchant la réplication inappropriée à partir de oriC et des R-loops et en agissant avec RecQ pour résoudre des intermédiaires de recombinaison RecA-dépendants afin de permettre la ségrégation des chromosomes.

On Szegö’s Type Theorems

This study is to look the effect of change in the ordering of the Fourier system on Szegö’s classical observations of asymptotic distribution of eigenvalues of finite Toeplitz forms.This is done by checking proofs and Szegö’s properties in the new set up.The Fourier system is unconditional [19], any arbitrary ordering of the Fourier system forms a basis for the Hilbert space L2 [-Π, Π].Here study about the classical Szegö’s theorem.Szegö’s type theorem for operators in L2(R+) and check its validity for certain multiplication operators.Since the trigonometric basis is not available in L2(R+) or in L2(R) .This study discussed about the classes of orderings of Haar System in L2 (R+) and in L2(R) in which Szegö’s Type TheoreT Am is valid for certain multiplication operators.It is divided into two sections. In the first section there is an ordering to Haar system in L2(R+) and prove that with respect to this ordering, Szegö’s Type theorem holds for general class of multiplication operators Tƒ with multiplier ƒ ε L2(R+), subject to some conditions on ƒ.Finally in second section more general classes of ordering of Haar system in L2(R+) and in L2(R) are identified in such a way that for certain classes of multiplication operators the asymptotic distribution of eigenvalues exists.

Modeling and Analysis of Some Heavy Tailed Time Series

The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

Analysis of some Stochastic models in inventories and Queues

The thesis entitled Analysis of Some Stochastic Models in Inventories and Queues. This thesis is devoted to the study of some stochastic models in Inventories and Queues which are physically realizable, though complex. It contains a detailed analysis of the basic stochastic processes underlying these models. In this thesis, (s,S) inventory systems with nonidentically distributed interarrival demand times and random lead times, state dependent demands, varying ordering levels and perishable commodities with exponential life times have been studied. The queueing system of the type Ek/Ga,b/l with server vacations, service systems with single and batch services, queueing system with phase type arrival and service processes and finite capacity M/G/l queue when server going for vacation after serving a random number of customers are also analysed. The analogy between the queueing systems and inventory systems could be exploited in solving certain models. In vacation models, one important result is the stochastic decomposition property of the system size or waiting time. One can think of extending this to the transient case. In inventory theory, one can extend the present study to the case of multi-item, multi-echelon problems. The study of perishable inventory problem when the commodities have a general life time distribution would be a quite interesting problem. The analogy between the queueing systems and inventory systems could be exploited in solving certain models.

Study on period search methods of variable stars: Application to ASAS and CRTS databases

Study on variable stars is an important topic of modern astrophysics. After the invention of powerful telescopes and high resolving powered CCD’s, the variable star data is accumulating in the order of peta-bytes. The huge amount of data need lot of automated methods as well as human experts. This thesis is devoted to the data analysis on variable star’s astronomical time series data and hence belong to the inter-disciplinary topic, Astrostatistics. For an observer on earth, stars that have a change in apparent brightness over time are called variable stars. The variation in brightness may be regular (periodic), quasi periodic (semi-periodic) or irregular manner (aperiodic) and are caused by various reasons. In some cases, the variation is due to some internal thermo-nuclear processes, which are generally known as intrinsic vari- ables and in some other cases, it is due to some external processes, like eclipse or rotation, which are known as extrinsic variables. Intrinsic variables can be further grouped into pulsating variables, eruptive variables and flare stars. Extrinsic variables are grouped into eclipsing binary stars and chromospheri- cal stars. Pulsating variables can again classified into Cepheid, RR Lyrae, RV Tauri, Delta Scuti, Mira etc. The eruptive or cataclysmic variables are novae, supernovae, etc., which rarely occurs and are not periodic phenomena. Most of the other variations are periodic in nature. Variable stars can be observed through many ways such as photometry, spectrophotometry and spectroscopy. The sequence of photometric observa- xiv tions on variable stars produces time series data, which contains time, magni- tude and error. The plot between variable star’s apparent magnitude and time are known as light curve. If the time series data is folded on a period, the plot between apparent magnitude and phase is known as phased light curve. The unique shape of phased light curve is a characteristic of each type of variable star. One way to identify the type of variable star and to classify them is by visually looking at the phased light curve by an expert. For last several years, automated algorithms are used to classify a group of variable stars, with the help of computers. Research on variable stars can be divided into different stages like observa- tion, data reduction, data analysis, modeling and classification. The modeling on variable stars helps to determine the short-term and long-term behaviour and to construct theoretical models (for eg:- Wilson-Devinney model for eclips- ing binaries) and to derive stellar properties like mass, radius, luminosity, tem- perature, internal and external structure, chemical composition and evolution. The classification requires the determination of the basic parameters like pe- riod, amplitude and phase and also some other derived parameters. Out of these, period is the most important parameter since the wrong periods can lead to sparse light curves and misleading information. Time series analysis is a method of applying mathematical and statistical tests to data, to quantify the variation, understand the nature of time-varying phenomena, to gain physical understanding of the system and to predict future behavior of the system. Astronomical time series usually suffer from unevenly spaced time instants, varying error conditions and possibility of big gaps. This is due to daily varying daylight and the weather conditions for ground based observations and observations from space may suffer from the impact of cosmic ray particles. Many large scale astronomical surveys such as MACHO, OGLE, EROS, xv ROTSE, PLANET, Hipparcos, MISAO, NSVS, ASAS, Pan-STARRS, Ke- pler,ESA, Gaia, LSST, CRTS provide variable star’s time series data, even though their primary intention is not variable star observation. Center for Astrostatistics, Pennsylvania State University is established to help the astro- nomical community with the aid of statistical tools for harvesting and analysing archival data. Most of these surveys releases the data to the public for further analysis. There exist many period search algorithms through astronomical time se- ries analysis, which can be classified into parametric (assume some underlying distribution for data) and non-parametric (do not assume any statistical model like Gaussian etc.,) methods. Many of the parametric methods are based on variations of discrete Fourier transforms like Generalised Lomb-Scargle peri- odogram (GLSP) by Zechmeister(2009), Significant Spectrum (SigSpec) by Reegen(2007) etc. Non-parametric methods include Phase Dispersion Minimi- sation (PDM) by Stellingwerf(1978) and Cubic spline method by Akerlof(1994) etc. Even though most of the methods can be brought under automation, any of the method stated above could not fully recover the true periods. The wrong detection of period can be due to several reasons such as power leakage to other frequencies which is due to finite total interval, finite sampling interval and finite amount of data. Another problem is aliasing, which is due to the influence of regular sampling. Also spurious periods appear due to long gaps and power flow to harmonic frequencies is an inherent problem of Fourier methods. Hence obtaining the exact period of variable star from it’s time series data is still a difficult problem, in case of huge databases, when subjected to automation. As Matthew Templeton, AAVSO, states “Variable star data analysis is not always straightforward; large-scale, automated analysis design is non-trivial”. Derekas et al. 2007, Deb et.al. 2010 states “The processing of xvi huge amount of data in these databases is quite challenging, even when looking at seemingly small issues such as period determination and classification”. It will be beneficial for the variable star astronomical community, if basic parameters, such as period, amplitude and phase are obtained more accurately, when huge time series databases are subjected to automation. In the present thesis work, the theories of four popular period search methods are studied, the strength and weakness of these methods are evaluated by applying it on two survey databases and finally a modified form of cubic spline method is intro- duced to confirm the exact period of variable star. For the classification of new variable stars discovered and entering them in the “General Catalogue of Vari- able Stars” or other databases like “Variable Star Index“, the characteristics of the variability has to be quantified in term of variable star parameters.

Some New Classes of Orthogonal Polynomials and Special Functions

In dieser Dissertation präsentieren wir zunächst eine Verallgemeinerung der üblichen Sturm-Liouville-Probleme mit symmetrischen Lösungen und erklären eine umfassendere Klasse. Dann führen wir einige neue Klassen orthogonaler Polynome und spezieller Funktionen ein, welche sich aus dieser symmetrischen Verallgemeinerung ableiten lassen. Als eine spezielle Konsequenz dieser Verallgemeinerung führen wir ein Polynomsystem mit vier freien Parametern ein und zeigen, dass in diesem System fast alle klassischen symmetrischen orthogonalen Polynome wie die Legendrepolynome, die Chebyshevpolynome erster und zweiter Art, die Gegenbauerpolynome, die verallgemeinerten Gegenbauerpolynome, die Hermitepolynome, die verallgemeinerten Hermitepolynome und zwei weitere neue endliche Systeme orthogonaler Polynome enthalten sind. All diese Polynome können direkt durch das neu eingeführte System ausgedrückt werden. Ferner bestimmen wir alle Standardeigenschaften des neuen Systems, insbesondere eine explizite Darstellung, eine Differentialgleichung zweiter Ordnung, eine generische Orthogonalitätsbeziehung sowie eine generische Dreitermrekursion. Außerdem benutzen wir diese Erweiterung, um die assoziierten Legendrefunktionen, welche viele Anwendungen in Physik und Ingenieurwissenschaften haben, zu verallgemeinern, und wir zeigen, dass diese Verallgemeinerung Orthogonalitätseigenschaft und -intervall erhält. In einem weiteren Kapitel der Dissertation studieren wir detailliert die Standardeigenschaften endlicher orthogonaler Polynomsysteme, welche sich aus der üblichen Sturm-Liouville-Theorie ergeben und wir zeigen, dass sie orthogonal bezüglich der Fisherschen F-Verteilung, der inversen Gammaverteilung und der verallgemeinerten t-Verteilung sind. Im nächsten Abschnitt der Dissertation betrachten wir eine vierparametrige Verallgemeinerung der Studentschen t-Verteilung. Wir zeigen, dass diese Verteilung gegen die Normalverteilung konvergiert, wenn die Anzahl der Stichprobe gegen Unendlich strebt. Eine ähnliche Verallgemeinerung der Fisherschen F-Verteilung konvergiert gegen die chi-Quadrat-Verteilung. Ferner führen wir im letzten Abschnitt der Dissertation einige neue Folgen spezieller Funktionen ein, welche Anwendungen bei der Lösung in Kugelkoordinaten der klassischen Potentialgleichung, der Wärmeleitungsgleichung und der Wellengleichung haben. Schließlich erklären wir zwei neue Klassen rationaler orthogonaler hypergeometrischer Funktionen, und wir zeigen unter Benutzung der Fouriertransformation und der Parsevalschen Gleichung, dass es sich um endliche Orthogonalsysteme mit Gewichtsfunktionen vom Gammatyp handelt.

Lower Bounds for Nonforgetting Restarting Automata and CD-Systems of Restarting Automata

The nonforgetting restarting automaton is a generalization of the restarting automaton that, when executing a restart operation, changes its internal state based on the current state and the actual contents of its read/write window instead of resetting it to the initial state. Another generalization of the restarting automaton is the cooperating distributed system (CD-system) of restarting automata. Here a finite system of restarting automata works together in analyzing a given sentence, where they interact based on a given mode of operation. As it turned out, CD-systems of restarting automata of some type X working in mode =1 are just as expressive as nonforgetting restarting automata of the same type X. Further, various types of determinism have been introduced for CD-systems of restarting automata called strict determinism, global determinism, and local determinism, and it has been shown that globally deterministic CD-systems working in mode =1 correspond to deterministic nonforgetting restarting automata. Here we derive some lower bound results for some types of nonforgetting restarting automata and for some types of CD-systems of restarting automata. In this way we establish separations between the corresponding language classes, thus providing detailed technical proofs for some of the separation results announced in the literature.

Systems of Parallel Communicating Restarting Automata

In der vorliegenden Dissertation werden Systeme von parallel arbeitenden und miteinander kommunizierenden Restart-Automaten (engl.: systems of parallel communicating restarting automata; abgekürzt PCRA-Systeme) vorgestellt und untersucht. Dabei werden zwei bekannte Konzepte aus den Bereichen Formale Sprachen und Automatentheorie miteinander vescrknüpft: das Modell der Restart-Automaten und die sogenannten PC-Systeme (systems of parallel communicating components). Ein PCRA-System besteht aus endlich vielen Restart-Automaten, welche einerseits parallel und unabhängig voneinander lokale Berechnungen durchführen und andererseits miteinander kommunizieren dürfen. Die Kommunikation erfolgt dabei durch ein festgelegtes Kommunikationsprotokoll, das mithilfe von speziellen Kommunikationszuständen realisiert wird. Ein wesentliches Merkmal hinsichtlich der Kommunikationsstruktur in Systemen von miteinander kooperierenden Komponenten ist, ob die Kommunikation zentralisiert oder nichtzentralisiert erfolgt. Während in einer nichtzentralisierten Kommunikationsstruktur jede Komponente mit jeder anderen Komponente kommunizieren darf, findet jegliche Kommunikation innerhalb einer zentralisierten Kommunikationsstruktur ausschließlich mit einer ausgewählten Master-Komponente statt. Eines der wichtigsten Resultate dieser Arbeit zeigt, dass zentralisierte Systeme und nichtzentralisierte Systeme die gleiche Berechnungsstärke besitzen (das ist im Allgemeinen bei PC-Systemen nicht so). Darüber hinaus bewirkt auch die Verwendung von Multicast- oder Broadcast-Kommunikationsansätzen neben Punkt-zu-Punkt-Kommunikationen keine Erhöhung der Berechnungsstärke. Desweiteren wird die Ausdrucksstärke von PCRA-Systemen untersucht und mit der von PC-Systemen von endlichen Automaten und mit der von Mehrkopfautomaten verglichen. PC-Systeme von endlichen Automaten besitzen bekanntermaßen die gleiche Ausdrucksstärke wie Einwegmehrkopfautomaten und bilden eine untere Schranke für die Ausdrucksstärke von PCRA-Systemen mit Einwegkomponenten. Tatsächlich sind PCRA-Systeme auch dann stärker als PC-Systeme von endlichen Automaten, wenn die Komponenten für sich genommen die gleiche Ausdrucksstärke besitzen, also die regulären Sprachen charakterisieren. Für PCRA-Systeme mit Zweiwegekomponenten werden als untere Schranke die Sprachklassen der Zweiwegemehrkopfautomaten im deterministischen und im nichtdeterministischen Fall gezeigt, welche wiederum den bekannten Komplexitätsklassen L (deterministisch logarithmischer Platz) und NL (nichtdeterministisch logarithmischer Platz) entsprechen. Als obere Schranke wird die Klasse der kontextsensitiven Sprachen gezeigt. Außerdem werden Erweiterungen von Restart-Automaten betrachtet (nonforgetting-Eigenschaft, shrinking-Eigenschaft), welche bei einzelnen Komponenten eine Erhöhung der Berechnungsstärke bewirken, in Systemen jedoch deren Stärke nicht erhöhen. Die von PCRA-Systemen charakterisierten Sprachklassen sind unter diversen Sprachoperationen abgeschlossen und einige Sprachklassen sind sogar abstrakte Sprachfamilien (sogenannte AFL's). Abschließend werden für PCRA-Systeme spezifische Probleme auf ihre Entscheidbarkeit hin untersucht. Es wird gezeigt, dass Leerheit, Universalität, Inklusion, Gleichheit und Endlichkeit bereits für Systeme mit zwei Restart-Automaten des schwächsten Typs nicht semientscheidbar sind. Für das Wortproblem wird gezeigt, dass es im deterministischen Fall in quadratischer Zeit und im nichtdeterministischen Fall in exponentieller Zeit entscheidbar ist.

Evaluation of auditory-visual speech perception in individuals diagnosed with dementia of the Alzheimer's type

Auditory-visual speech perception testing was completed using wordandconsonant-level stimuli in individuals with known degrees of dementia of theAlzheimer’s type. The correlations with the cognitive measures and the speechperception measures (A-only, V-only, AV, VE or AE) did not reveal significantrelationships.

Boundary integral equations on unbounded rough surfaces: Fredholmness and the finite section method

We consider a class of boundary integral equations that arise in the study of strongly elliptic BVPs in unbounded domains of the form $D = \{(x, z)\in \mathbb{R}^{n+1} : x\in \mathbb{R}^n, z > f(x)\}$ where $f : \mathbb{R}^n \to\mathbb{R}$ is a sufficiently smooth bounded and continuous function. A number of specific problems of this type, for example acoustic scattering problems, problems involving elastic waves, and problems in potential theory, have been reformulated as second kind integral equations $u+Ku = v$ in the space $BC$ of bounded, continuous functions. Having recourse to the so-called limit operator method, we address two questions for the operator $A = I + K$ under consideration, with an emphasis on the function space setting $BC$. Firstly, under which conditions is $A$ a Fredholm operator, and, secondly, when is the finite section method applicable to $A$?

The role of voltage gated T-type Ca2+ channel isoforms in mediating "capacitative" Ca2+ entry in cancer cells

The mechanism by which Ca2+ enters electrically non-excitable cells is unclear. The sensitivity of the Ca2+ entry pathway in electrically non-excitable cells to inhibition by extracellular Ni2+ was used to direct the synthesis of a library of simple, novel compounds. These novel compounds inhibit Ca2+ entry into and, consequently, proliferation of several cancer cell lines. They showed stereoselective inhibition of proliferation and Ca2+ influx with identical stereoselective inhibition of heterologously expressed Cav3.2 isoform of T-type Ca2+ channels. Proliferation of human embryonic kidney (HEK)293 cells transfected with the Cav3.2 Ca2+ channel was also blocked. Cancer cell lines sensitive to our compounds express message for the Cav3.2 T-type Ca2+ channel isoform, its delta25B splice variant, or both, while a cell line resistant to our compounds does not. These observations raise the possibility that clinically useful drugs can be designed based upon the ability to block these Ca2+ channels.

Correlation-type structure activity relationships for the kinetics of gas-phase RO2 self-reactions and reaction with HO2

Structure activity relationships (SARs) are presented for the gas-phase reactions of RO2 with HO2, and the self- and cross-reactions of RO2. For RO2+HO2 the SAR is based upon a correlation between the logarithm of the measured rate coefficient and a calculated ionisation potential for the molecule R-CH=CH2, R being the same group in both the radical and molecular analogue. The correlation observed is strong and only for one RO2 species does the measured rate coefficient deviate by more than a factor of two from the linear least-squares regression line. For the self- and cross-reactions of RO2 radicals, the SAR is based upon a correlation between the logarithm of the measured rate coefficient and the calculated electrostatic potential (ESP) at the equivalent carbon atom in the RH molecule to which oxygen is attached in RO2, again R being the same group in the molecule and the radical. For cases where R is a simple alkyl-group, a strong linear correlation observed. For RO2 radicals which contain lone pair-bearing substituents and for which the calculated ESP<-0.05 self-reaction rate coefficients appear to be insensitive to the value of the ESP. For RO2 of this type with ESP>-0.05 a linear relationship between log k and the ESP is again observed. Using the relationships, 84 out of the 85 rate coefficients used to develop the SARs are predicted to within a factor of three of their measured values. A relationship is also presented that allows the prediction of the Arrhenius parameters for the self-reactions of simple alkyl RO2 radicals. On the basis of the correlations, predictions of room-temperature rate coefficients are made for a number of atmospherically important peroxyl-peroxyl radical reactions. (C) 2003 Elsevier Ltd. All rights reserved.