The transportation system is vital to the nation’s economic growth and stability, as it provides mobility for commuters while supporting the United States’ ability to compete in an increasingly competitive global economy. State Transportation Agencies across the country continue to face many challenges to repair and enhance highway infrastructure to meet the rapid increasing transportation needs. One of these challenges is maintaining an adequate and efficient agency staff. In order to effectively plan for future staffing levels, State Transportation Agencies need a method for forecasting long term staffing requirements. However, current methods in use cannot function without well-defined projects and therefore making long term forecasts is difficult. This dissertation seeks to develop a dynamic model which captures the feedback mechanisms within the system that determines highway staffing requirements. The system dynamics modeling methodology was used to build the forecasting model. The formal model was based on dynamic hypotheses derived from literature review and interviews with transportation experts. Both qualitative and quantitative data from literature, federal and state database were used to support the values and equations in the model. The model integrates State Transportation Agencies’ strategic plans, funding situations and workforce management strategies while determining future workforce requirements, and will hopefully fill the absence of long-term staffing level forecasting tools at State Transportation Agencies. By performing sensitivity simulations and statistical screening on possible drivers of the system behavior, the dynamic impacts of desired highway pavement performance level, availability of road fund and bridge fund on the required numbers of Engineers and Technicians throughout a 25-year simulation period were closely examined. Staffing strategies such as recruiting options (in-house vs. consultants) and hiring levels (entry level vs. senior level) were tested. Finally the model was calibrated using input data specific to Kentucky to simulate an expected retirement wave and search for solutions to address temporary staffing shortage.

Thesis (MScEng (Electrical and Electronic Engineering))--Stellenbosch University, 2008. / This thesis discusses the design, development and measured results of a phase-locked loop based frequency synthesiser for X-band Doppler radar. The objective is to obtain phase noise comparable or lower than that typically achieved with direct analogue frequency synthesis techniques. To meet this objective, a theoretical study of the noise contributions of individual components of the synthesiser and their effect on the total phase noise within and outside the loop bandwidth of the PLL is performed. The effect of different phase margins on the closed-loop frequency response of the PLL, and hence the total phase noise, is investigated. Based on the results, an optimal phase-frequency detector reference frequency, loop bandwidth, adequate phase margin, and suitable components are chosen for optimal phase noise performance. The total phase noise at the output of the synthesiser is calculated and it is shown that the phase noise specification can be met. A significant part of this thesis is devoted to the design, modelling and characterisation of a frequency multiplier, as well as to a combline and interdigital bandpass filter required for the frequency synthesiser. In the first case, a piecewise linear circuit model is used to model the behaviour of the nonlinear multiplier circuit. Fourier theory is used to calculate the large-signal driving point input and output impedances of the nonlinear circuit, enabling the computation of the circuit elements for the input and output matching networks. The measured response of the frequency multiplier under various different operating conditions is presented and discussed. The design of the microwave bandpass filters is based on the theory of coupling and external quality factors. To aid in the verification and optimisation of the design, a software simulation tool is used. The presented S-parameter measurements of the filters show how well the theory matches with what is obtained in practice. The measured spectral and phase noise response of various components comprising the synthesiser, are discussed. These measurements provide insight into the response of individual components under different operating conditions and show the behaviour of important subsystems of the synthesiser. The thesis culminates in the presentation of the measured phase noise of the complete synthesiser. It is shown how well the measured phase noise correlates with the calculated phase noise. In addition, the measured spectral content and transient behaviour of the synthesiser are investigated and discussed. High power spurious components at some output frequencies are indentified and reduced. The feasibility of using the developed prototype phase-locked loop based frequency synthesiser for coherent X-band Doppler radar is discussed and demonstrated.

All human chromosomes end with protective structures called telomeres, which consist of thousands of double-stranded TTAGGG repeats and end in a 3’ guanine-rich overhang. These structures shorten normally during each round of replication, and extremely short telomeres along with telomere dysfunction are thought to contribute to the development of aging and cancer. Although many proteins have roles in telomere maintenance, WRN, which is a 3’ to 5’ helicase that is deficient in the premature aging disorder Werner’s syndrome, has been proposed to play multiple roles at telomeres. In this study, I focus on the effect of telomeric sequences and/or structures formed during DNA replication or recombination and how WRN functions at these sites. This study suggests that WRN may promote proper replication of telomeres by accurately aligning telomeric sequences during replication fork regression, potentially the first step in responding to a blockage, such as DNA damage. However, even in the presence of WRN, replication of telomeric sequences is difficult, possibly due to the ability of G-rich sequences to form secondary structures such as G-quadruplexes. I demonstrate that the translesion polymerase pol η, as well as a variety of other polymerases, is unable to synthesize past an intramolecular G-quadruplex formed from telomeric sequence on the template strand. Furthermore, in physiological salt concentrations, WRN favors binding and unwinding a structure that mimics a strand invasion intermediate over other similar structures especially when it possesses G-telomeric sequence. In addition, WRN promotes unwinding of these structures in a direction that would promote additional annealing and strand invasion, supporting a role for WRN in promoting telomeric recombination and formation of a T-loop, a proposed protective structure specific to telomeres. Overall, the data suggest that telomeres may pose problems in replication due to the G-rich, repeating nature of the structures, while WRN may aid in promoting proper replication at these and other replication blocks. Furthermore, WRN may play a role in promoting additional formation of T-loops and other telomeric recombination, thus supporting the relationship of WRN, telomere maintenance, and potentially development of certain aging characteristics.

Mixed-signal designs are becoming more and more complex every day. In order to adapt to the new market requirements, a formal process for design and verification of mixed signal systems i. e. top-down design and bottom-up verification methodology is required. This methodology has already been established for digital design. The goal of this research is to propose a new design methodology for mixed signal systems. In the first two chapters of this thesis, the need for a mixed signal design flow based on top-down design methodology will be discussed. The proposed design flow is based on behavioral modeling of the mixed signal system using one of the mixed signal behavioral modeling languages. These models can be used for design and verification through different steps of the design from system level modeling to final physical design. The other advantage of the proposed flow is analog and digital co-design. In the remaining chapters of this thesis, the proposed design flow was verified by designing an 800 MHz mixed signal PLL. The PLL uses a charge pump phase frequency detector, a single capacitor loop filter, and a feed forward error correction architecture using an active damping control circuit instead of passive resistor in loop filter. The design was done in 0. 18- <i>??</i> m CMOS process technology.

Doctor of Philosophy / Department of Electrical and Computer Engineering / Pietro Poggi-Corradini / Caterina M. Scoglio / The modulus of a family of walks quanti es the richness of the family by favoring having many short walks over a few longer ones. In this dissertation, we investigate various families of walks to study new measures for quantifying network properties using modulus. The proposed new measures are compared to other known quantities. Our proposed method is based on walks on a network, and therefore will work in great generality. For instance, the networks we consider can be directed, multi-edged, weighted, and even contain disconnected parts. We study the popular centrality measure known in some circles as information centrality, also known as e ective conductance centrality. After reinterpreting this measure in terms of modulus of families of walks, we introduce a modi cation called shell modulus centrality, that relies on the egocentric structure of the graph. Ego networks are networks formed around egos with a speci c order of neighborhoods. We then propose e cient analytical and approximate methods for computing these measures on both directed and undirected networks. Finally, we describe a simple method inspired by shell modulus centrality, called general degree, which improves simple degree centrality and could prove to be a useful tool for practitioners in the applied sciences. General degree is useful for detecting the best set of nodes for immunization. We also study the structure of loops in networks using the notion of modulus of loop families. We introduce a new measure of network clustering by quantifying the richness of families of (simple) loops. Modulus tries to minimize the expected overlap among loops by spreading the expected link-usage optimally. We propose weighting networks using these expected link-usages to improve classical community detection algorithms. We show that the proposed method enhances the performance of certain algorithms, such as spectral partitioning and modularity maximization heuristics, on standard benchmarks. Computing loop modulus bene ts from e cient algorithms for nding shortest loops, thus we propose a deterministic combinatorial algorithm that nds a shortest cycle in graphs. The proposed algorithm reduces the worst case time complexity of the existing combinatorial algorithms to O(nm) or O(hkin2 log n) while visiting at most m - n + 1 cycles (size of cycle basis). For most empirical networks with average degree in O(n1􀀀 ) our algorithm is subcubic.

Transcription termination of RNA polymerase II (Pol II) in mammals requires a functional poly(A) signal and either downstream pause sites or co-transcriptional cleavage (CoTC) sequences together with 3’transcript degradation by the nuclear 5’-3’ exonuclease Xrn2. However the molecular mechanism of pause-dependent transcriptional termination is not yet fully understood. This thesis investigates the molecular role of R-loop structures in pause-dependent transcriptional termination of mammalian genes. The results described in Chapters 3 and 4 indicate that nascent transcripts form RNA/DNA hybrid structures (R-loops) behind elongating Pol II and are especially prevalent over G-rich pause sites positioned downstream of gene poly(A) signals. Senataxin, a helicase protein and the human homologue of the yeast Sen1, acts to resolve these R-loop structures and by so doing allows access of Xrn2 at 3’ cleavage poly(A) sites. This ultimately leads to efficient Pol II termination. In effect R-loops formed over G-rich pause sites, followed by their resolution by senataxin, are required for efficient pause-dependent transcriptional termination. In addition to this, the 3’ end processing factor, Pcf11 is also involved in this process. Experiments presented in the final part of this study reveal a link between R-loops and RNAi-dependent H3K9me2 formation over G-rich termination regions. Overall my results suggest that R-loop structures and the H3K9me2 repressive mark over pause regions are important features of Pol II pause-dependent transcriptional termination of mammalian genes.

In the first part of this thesis, we study the duality of Wilson loops and M2-branes in AdS₄/CFT₃. We focus on supersymmetric M-theory solutions on AdS₄xY₇ that have a superconformal dual description on S³ = ?AdS⁴. We will find that the Hamiltonian function h_M for the M-theory circle plays an important role in the duality. We show that an M2-brane wrapping the M-theory circle is supersymmetric precisely at the critical points of h_M, and moreover the value of this function at those points determines the M2-brane actions. Such a configuration determines the holographic dual of a Wilson loop for a Hopf circle in S³. We find agreement in large classes of examples between the Wilson loop and its dual M2-brane and also that the image h_M(Y₇) determines the range of support of the eigenvalues in the dual large N matrix model, with the critical points of h_M mapping to points where the derivative of the eigenvalue density is discontinuous. We will then move away from the three-sphere and construct gravity duals to a broad class of N=2 supersymmetric gauge theories defined on a general class of three-manifold geometries. The gravity backgrounds are based on Euclidean self-dual solutions to four-dimensional gauged supergravity. As well as constructing new examples, we prove in general that for solutions defined on the four-ball the gravitational free energy depends only on the supersymmetric Killing vector. Our result agrees with the large N limit of the free energy of the dual gauge theory, computed using localisation. This constitutes an exact check of the gauge/gravity correspondence for a very broad class of gauge theories defined on a general class of background three-manifold geometries. To further verify that our gravitational backgrounds are indeed dual to field theories on their boundaries, we compute Wilson loops and their M2-brane duals in this general setting. We find that the Wilson loop is given by a simple closed formula which depends on the background geometry only through the supersymmetric Killing vector field. The supergravity dual M2-brane precisely reproduces this large N field theory result. This constitutes a further check of AdS₄/CFT₃ for a very broad class of examples.

Les chromosomes sont organisés en plusieurs niveaux hiérarchiques de repliements de la chromatine. Cette organisation spatiale de la chromatine dans le noyau a été impliquée dans la régulation de nombreux processus cellulaires comme la réplication ou la transcription. En effet, différentes expériences suggèrent que la chromatine est organisée en boucles, dont les bases seraient maintenues attachées ensemble, formant une structure qui serait un soutien structurel de la chromatine.Mon projet de thèse a visé à identifier les séquences d'ADN constituant la base de ces boucles de la chromatine par hybridation sur puces. Notre étude a été réalisée sur des MEF asynchrones et synchronisées en G0/G1 afin d'établir la dynamique des MARs au cours du cycle cellulaire.Nos résultats montrent que les MARs constituent des grands domaines, qui sont associés de façon significative avec les domaines d'ADN liées à la Lamine B1 et les domaines tardifs du timing de réplication. L'analyse des MARs ayant été réalisée sur des MEFs synchronisées en G0, les domaines de timing seraient donc déjà définis en G0/G1. L'analyse de plusieurs marques des histones suggère que les MARs sont associées à la chromatine transcriptionnellement inactive. En parallèle, nous avons réalisé une analyse protéomique de la matrice. Celle-ci a permis de valider notre approche expérimentale mais nous a aussi donné l'opportunité de caractériser la matrice nucléaire d'un point de vue protéique.L'ensemble de nos résultats révèle que les séquences d'ADN liées à la matrice nucléaire constituent une zone de répression, tant au niveau transcriptionnel que réplicatif. / Chromosomes are organised into several hierarchical levels of chromatin compaction. This spatial organization of chromatin in the nucleus has been involved in regulating many cellular processes such as DNA replication and transcription. Indeed, different experiments suggest that chromatin is organized in loops, whose bases are kept attached together, forming a structure, often called the nuclear matrix, acting as a structural support of the chromatin. My project was to identify the DNA sequences that belong to the bases of these chromatin loops. Matrix-attached regions (MARs) were mapped by hybridization on microarrays. This study was performed on asynchronous as well as G0/G1-phase synchronized MEFs to establish the dynamics of MARs during the cell cycle. MARs were found in megabase-sized domains, with sequences significantly related to previously-published Lamin B1 associated domains and replication timing domains. Since our analysis of MARs was performed on G0-synchronized MEFs, our data strongly suggest that the timing domains might already be defined in G0/G1. Analysis of several histone marks suggested that MARs were associated with transcriptionally-repressed chromatin. In parallel, we also performed a proteomic analysis of our matrix preparations, and found known "matrix-attached" proteins, thus validating our experimental approach, plus other components that permitted a better characterization of the nuclear matrix. Taken together, our results show that DNA sequences bound to the nuclear matrix constitute a repressive zone, at the transcription and replication levels.

Nous nous intéressons aux lacets markoviens définis dans le cadre de la théorie des chaînes de Markov à temps continu sur un espace d'états discret. Ce sujet a notamment été étudié par Le Jan [LJ11] et Sznitman [Szn12]. En contraste avec ces références, nous ne supposerons pas la symétrie de la chaîne et nous intéresserons plutôt au cas infini. Tous les résultats sont présentés en termes de générateur de semi-groupe. En comparaison avec [LJ11], certaines preuves ont été détaillées ou améliorées.Nous fournissons par ailleurs quelques résultats sur les amas de boucles (voir [LJL12] dans le cas symétrique). Nous traitons notamment l'exemple du cercle discret. Nous étudions aussi les arbres couvrants définit par l'algorithme de Wilson dans le cas asymétrique.Dans la dernière partie, nous considérons la proportion des lacets couvrants l'espace. En utilisant la limite du spectre, nous donnons une expression générale de la limite de cette proportion pour une suite de graphes. Comme une application, nous donnons deux exemples concrets dans lesquels une transition de phase apparaît. / We are interested in Markov laces defined in the framework of the theory of Markov chains in continuous time on a discrete state space. This particular subject has been studied by Le Jan [LJ11] and Sznitman [Szn12]. In contrast to these references, we do not assume the reversibility of the chain and we are mostly interested in the case of countable state space. All the results are presented in terms of the generator of semigroup. In comparison with [LJ11], some demonstration has been detailed or improved.We also provide some results on the loop clusters (see [LJL12] in the reversible case). In particular, we study the example of discrete circle. We also study the spanning tree algorithm defined by Wilson in the non-symmetric case.In the last part, we consider the proportion of loops covering the whole space. Using the limit of the spectrums, we give a general expression for the limit of this ratio for a sequence of graphs. As an application, we give two examples in which a phase transition occurs.

Background: The Circular Economy model came as an alternative to the linear “use and dispose” production system. It argues to promote an economic order that can address the waste of aftermarket goods and a more efficient use of resources and raw materials. It further promises economic gains from a more efficient resource management and extended use of products lifecycle, in conjunction with new employment opportunities that arise as a result of new business models and industrial processes. Whilst the Circular Economy is surely a departure from traditional economic systems, there has been not enough debate on the full impacts as well as possible unintended consequences of its implementation.    Purpose: The purpose is to examine the Circular Economy adoption approach in the Jönköping county in Sweden and how this approach contributes to sustainability improvement.  Purpose: The purpose is to examine the Circular Economy adoption approach in the Jönköping county in Sweden and how this approach contributes to sustainability improvement.  Method: This is an exploratory research which is based on a qualitative design with an inductive approach and interpretive paradigm. The research follows a case study of a pilot project to help SMEs in Jönköping county - Sweden, to implement Circular Economy. The primary data is collected through semi-structured interviews with the project coordinators.  Conclusion: The Circular Economy Project in Jönköping takes into consideration all three resource loops on their implementation of CE based on Bocken et al (2016) resource loops. Embedding all three loops in the implementation of CE is a comprehensive and advanced form of circularity. Combined with the project high-level of sustainability awareness and their effort to integrate the social aspect into their Circular Economy, this research has placed the sustainability profile of the Project at the third level of the corporate sustainability stages presented by Landrum (2018), which is systemic sustainability.