VSS : a VHDL synthesis system

This report describes a register transfer synthesis system that allows a designer to interact with the design process. The designer can modify the compiled design by changing the input description, selecting optimization and mapping strategies, or graphically changing the generated design schematic. The VHDL language is used for input and output descriptions. An intermediate representation which incorporates signal typing and component attributes simplifies compilation and facilitates design optimization. The compilation process consists of two phases. First, a design composed of generic components is synthesized from the input description. Second, this design is translated into components from a particular library by a mapper and optimized by a logic optimizer. Redesign to new technologies can be accomplished by changing only the component library

A proposed synthesis method for Application-Specific Instruction Set Processors

Due to the rapid technology advancement in integrated circuit era, the need for the high computation performance together with increasing complexity and manufacturing costs has raised the demand for high-performance con fi gurable designs; therefore, the Application-Speci fi c Instruction Set Processors (ASIPs) are widely used in SoC design. The automated generation of software tools for ASIPs is a commonly used technique, but the automated hardware model generation is less frequently applied in terms of fi nal RTL implementations. Contrary to this, the fi nal register-transfer level models are usually created, at least partly, manually. This paper presents a novel approach for automated hardware model generation for ASIPs. The new solution is based on a novel abstract ASIP model and a modeling language (Algorithmic Microarchitecture Description Language, AMDL) optimized for this architecture model. The proposed AMDL-based pre-synthesis method is based on a set of pre-de fi ned VHDL implementation schemes, which ensure the qualities of the automatically generated register-transfer level models in terms of resource requirement and operation frequency. The design framework implementing the algorithms required by the synthesis method is also presented

Impact of fatty acid metabolism in breast cancer peritumoral tissue. Clinical and pathogenic aspects

El càncer de pit es el càncer més comú en dones i el segon càncer amb més morts relacionades. Conèixer el comportment de les cèl·lules tumorals en el seu microambient pot obrir noves posibilitats d’estudis i dianes terapèutiques en el futur. En aquesta tesi hem demostrat com factors alliberats pel teixit adipós, entre els quals cal destacar FABP4, potencien els diferents hallmarks del càncer. Tanmateix, hem demostrat que la comunicació és bidireccional entre cadascun dels elements del microambient, i que la transferència de lípids i el seu posterior metabolisme és diferencial entre les línies tumorals, cosa que podria explicar els seus diferents graus de tumorogenicitat. El sistema inmunitari, com element del microambient tumoral es veu modificat, generant un estat pro-inflamatori que es tradueix en el increment del mateix en les pacients de càncer de pit, que a més es veu relacionat positivament amb l’increment de FABP4. En aquest estudi s’ha demostrat que el perfil lipoproteic es veu modificat de forma significativa en aquestes dones, on hi ha un enriquiment de triglicèrids i colesterol a les diferents lipoproteïnes, las quals s’associen positivament amb l’estat pro-inflamatori de les pacients. L’estudi del sèrum per 1H-NMR també ens otorga coneixements sobre les alteraciones del perfil de LMWMs de les pacients, on trobem un increment de determinats aminoàcids en el sèrum de les mateixes. El coneixement de nous biomarcadors pot marcar noves vies diagnòstiques que ajuden a la selecció precoç i per tant en el millor pronòstic d’aquestes pacients.El cáncer de mama es el cáncer más común en mujeres y el segundo con más muertes relacionadas. Conocer el comportamiento de las células tumorales en su microambiente puede abrir nuevas posibilidades de estudios y dianas terapéuticas en un futuro. En esta tesis hemos demostrado como factores liberados por el tejido adiposo, entre los que cabe destacar FABP4 potencian los diferentes hallmarks del cáncer. Así mismo, hemos demostrado que la comunicación es bidireccional entre cada uno de los elementos del microambiente y que la transferencia de lípidos y su posterior metabolismo es diferencial entre las diferentes líneas tumorales, lo cual podría explicar sus diferentes grados de tumorogenicidad. El sistema inmunitario como elemento del microambiente tumoral se ve modificado por el mismo, generando un estado pro-inflamatorio que se traduce en un incremento del mismo en las pacientes de cáncer de mama, el cual se ve relacionado positivamente con el incremento de FABP4 en las mismas. Además, en este estudio se ha demostrado que el perfil lipoproteico se ve significativamente alterado en estas mujeres, donde hay un enriquecimiento de triglicéridos y colesterol en las diferentes lipoproteínas, las cuales también se asocian positivamente con el estado inflamatorio de las pacientes. El estudio del suero por 1H-NMR también nos otorga conocimiento sobre alteraciones en el perfil de LMWMs de las pacientes, donde encontramos un increment de determinados aminoácidos en el suero de las mismas. El conocimiento de nuevos bioamarcadores puede marcar nuevas vías de diagnóstico que ayuden a la detección temprana y por índole en el mejor pronóstico de estas pacienBreast cancer is the most common cancer in women and the second cancer with more related deaths. Knwoledge og the behavior of tumor cells within their microenvironment might open new research possibilities and new therapeutic tarjets in the future. In this doctoral thesis, we have demonstrated how diverse factors that are released by the adipose tissue, especially FABP4, are able to enhance the diverse cancer hallmarks. Moreover, we have demonstrated the birectionallity of the microenvironemnt crosstalk, as well as that the lipid transfer and their metabolism is different in the different submolecular BC types, thus might explain their different malignance grades. Tne immune system, as an element of the tumor microenvironment is altered by this crosstalk, by activating the pro-inflammatory pathways. This is translate to an enhancement of the pro-inflammatory status of BC patients. Interestingly, this status is positively correlated with the increment of FABP4 serum levels in BC patients. Moreover, this study has demonstrated that the liporpotein profile is notably altered in BC patients, where there is a cholesterol and triglycerides enrichement within the different lipoproteins. These changes have been positively correlated with the inflammatory status of our BC patients. The serum LMWMs analysis by 1H-NMR demonstrated that there was a disregulated serum levels of different aminoacids. Knowledge of new biomarks would open new diagnosis methods, that might help in an earliest diagnosis, hence in the BC patients’ prognosis

Innovative Lipid Biomarkers and Long-Term Outcomes:studies in patients treated with renal replacement therapy and in the general population

Cardiovascular disease is the leading cause of mortality in the developed world. Atherosclerosis, the main driving factor behind cardiovascular disease, is largely influenced by lipids. Patients with a decreased kidney function, such as dialysis patients or patients who have undergone a kidney transplantation are at a particularly high risk of cardiovascular disease. Furthermore, they can develop atherosclerotic lesions in the (transplanted) kidney, leading to further function decline and eventually kidney failure. Low density lipoproteins (LDL), the ‘bad’ cholesterol, and triglycerides promote the formation of atherosclerotic plaques. High density lipoprotein (HDL), the ‘good’ cholesterol is able to break down atherosclerosis and thereby lowers the risk of cardiovascular disease. In this thesis this process was evaluated in dialysis patients, which showed that they have a decreased ability of HDL to perform this protective effect. Furthermore, a novel protective effect of HDL was described, namely the ability to lower inflammation. This protective effect indeed leads to a lower risk of cardiovascular disease in the general population. A different way of describing lipid abnormalities, by using a ratio of triglycerides to the HDL, is better at identifying patients who are at risk of cardiovascular disease of kidney disease. Furthermore, a risk score developed for cardiovascular disease is also able to predict kidney disease, which lends evidence to the fact that both processes are driven by atherosclerosis. In conclusion, this thesis identified novel biomarkers for atherosclerosis and shows how important close attention to lipid control is in both kidney disease patients and the general population

Probabilistic Image Models and their Massively Parallel Architectures : A Seamless Simulation- and VLSI Design-Framework Approach

Algorithmic robustness in real-world scenarios and real-time processing capabilities are the two essential and at the same time contradictory requirements modern image-processing systems have to fulfill to go significantly beyond state-of-the-art systems. Without suitable image processing and analysis systems at hand, which comply with the before mentioned contradictory requirements, solutions and devices for the application scenarios of the next generation will not become reality. This issue would eventually lead to a serious restraint of innovation for various branches of industry. This thesis presents a coherent approach to the above mentioned problem. The thesis at first describes a massively parallel architecture template and secondly a seamless simulation- and semiconductor-technology-independent design framework for a class of probabilistic image models, which are formulated on a regular Markovian processing grid. The architecture template is composed of different building blocks, which are rigorously derived from Markov Random Field theory with respect to the constraints of \it massively parallel processing \rm and \it technology independence\rm. This systematic derivation procedure leads to many benefits: it decouples the architecture characteristics from constraints of one specific semiconductor technology; it guarantees that the derived massively parallel architecture is in conformity with theory; and it finally guarantees that the derived architecture will be suitable for VLSI implementations. The simulation-framework addresses the unique hardware-relevant simulation needs of MRF based processing architectures. Furthermore the framework ensures a qualified representation for simulation of the image models and their massively parallel architectures by means of their specific simulation modules. This allows for systematic studies with respect to the combination of numerical, architectural, timing and massively parallel processing constraints to disclose novel insights into MRF models and their hardware architectures. The design-framework rests upon a graph theoretical approach, which offers unique capabilities to fulfill the VLSI demands of massively parallel MRF architectures: the semiconductor technology independence guarantees a technology uncommitted architecture for several design steps without restricting the design space too early; the design entry by means of behavioral descriptions allows for a functional representation without determining the architecture at the outset; and the topology-synthesis simplifies and separates the data- and control-path synthesis. Detailed results discussed in the particular chapters together with several additional results collected in the appendix will further substantiate the claims made in this thesis

The COMPLEX reference framework for HW/SW co-design and power management supporting platform-based design-space exploration

n/

Development of a vascularized, induced pluripotent stem cell-derived liver-tissue mimic for therapeutic applications.

This dissertation describes the incorporation of several technologies (stem cells, gene therapy, tissue engineering and regenerative medicine) into a single project that aims to produce a liver-tissue mimic for therapeutic applications. The liver is arguably one of the most complex organs in the body. In addition to its remarkable capacity to regenerate, it performs a host of vital functions. As a result, its impairment has widespread systemic consequences. The work described herein focused on the liver in the context of cardiovascular disease and used the heritable disorder Familial Hypercholesterolemia (FH) as a clinical disease model. As (a) the only definitive cure for FH is currently liver transplant and (b) the availability of quality liver organs for transplant is critically low, these studies seek to develop a liver-tissue mimic comprised of two parts: functional hepatocyte-like cells (derived from induced pluripotent stem cells, or iPSC) and vascular support (provided by adipose-derived stromal vascular fraction (SVF)). The dissertation is divided into six sections. Chapter I provides an introductory overview and lists the aims and hypotheses for the dissertation. Chapter II provides a four-part background discussing cholesterol metabolism, the liver organ, stem cells, and the vasculature. Chapter III describes our efforts to generate a proof-of-concept liver-tissue mimic, using HepG2 as a hepatocyte model cell source and SVF cells as the vascular support system. As vascular support is critical for parenchymal survival and function, Chapter IV examines the mechanisms of spontaneous SVF vascular self-assembly. Chapter V discusses development of a patient-specific, therapeutic cell system. FH-patient dermal fibroblasts were programmed into iPSC using modRNA technology, and eventually subjected the iPSC to directed differentiation into hepatocyte-like cells. Yet, as the iPSC were derived from an FH patient, the cells required functional restoration of their LDL-R in order to impart any therapeutic benefit. To accomplish this, a novel episomal LDL-R plasmid containing (a) upstream regulatory control sequences that confer physiological feedback control of LDL-R expression and (b) Epstein-Barr sequences for episomal retention and replication was used. To mitigate any potential concerns associated with viral vectors, the iPSC were derived and corrected using non-viral modalities. These cells were combined with an SVF derived vascular support system to assess iPSC-HLC survival characteristics in vivo. Chapter VI provides a comprehensive discussion regarding our experimental efforts. These experiments demonstrate the development of a vascularized, iPSC-derived hepatocyte liver-tissue mimic that could potentially be used for therapeutic applications, such as for the treatment of FH. Efforts to create this tissue engineered liver construct were guided by three aims: (1) Assess the role of adipose SVF in providing vascular support to implanted parenchymal cells, (2) Evaluate and define the mechanism(s) of SVF vascular self-assembly, and (3) Restore the functionality of monogenic-deficient FH cells. These studies provide several proofs-of-principle towards the development of effective cell-based treatments, not only for FH, but also for other diseases classically requiring whole-organ transplantation

Multiple voltage scheme with frequency variation for power minimization of pipelined circuits at high-level synthesis

High-Level Synthesis (HLS) is defined as a translation process from a behavioral description into structural description. The high-level synthesis process consists of three interdependent phases: scheduling, allocation and binDing The order of the three phases varies depending on the design flow. There are three important quality measures used to support design decision, namely size, performance and power consumption. Recently, with the increase in portability, the power consumption has become a very dominant factor in the design of circuits. The aim of low-power high-level synthesis is to schedule operations to minimize switching activity and select low power modules while satisfying timing constraints. This thesis presents a heuristic that helps minimize power consumption by operating the functional units at multiple voltages and varied clock frequencies. The algorithm presented here deals with pipelined operations where multiple instance of the same operation are carried out. The algorithm was implemented using C++, on LINUX platform