Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

Importance of influx and efflux systems and xenobiotic metabolizing enzymes in intratumoral disposition of anticancer agents.

In this review, intratumoral drug disposition will be integrated into the wide range of resistance mechanisms to anticancer agents with particular emphasis on targeted protein kinase inhibitors. Six rules will be established: 1. There is a high variability of extracellular/intracellular drug level ratios; 2. There are three main systems involved in intratumoral drug disposition that are composed of SLC, ABC and XME enzymes; 3. There is a synergistic interplay between these three systems; 4. In cancer subclones, there is a strong genomic instability that leads to a highly variable expression of SLC, ABC or XME enzymes; 5. Tumor-expressed metabolizing enzymes play a role in tumor-specific ADME and cell survival and 6. These three systems are involved in the appearance of resistance (transient event) or in the resistance itself. In addition, this article will investigate whether the overexpression of some ABC and XME systems in cancer cells is just a random consequence of DNA/chromosomal instability, hypo- or hypermethylation and microRNA deregulation, or a more organized modification induced by transposable elements. Experiments will also have to establish if these tumor-expressed enzymes participate in cell metabolism or in tumor-specific ADME or if they are only markers of clonal evolution and genomic deregulation. Eventually, the review will underline that the fate of anticancer agents in cancer cells should be more thoroughly investigated from drug discovery to clinical studies. Indeed, inhibition of tumor expressed metabolizing enzymes could strongly increase drug disposition, specifically in the target cells resulting in more efficient therapies.

Conceptual models for designing information systems supporting the strategic analysis of technology environments

1 6 STRUCTURE OF THIS THESIS -Chapter I presents the motivations of this dissertation by illustrating two gaps in the current body of knowledge that are worth filling, describes the research problem addressed by this thesis and presents the research methodology used to achieve this goal. -Chapter 2 shows a review of the existing literature showing that environment analysis is a vital strategic task, that it shall be supported by adapted information systems, and that there is thus a need for developing a conceptual model of the environment that provides a reference framework for better integrating the various existing methods and a more formal definition of the various aspect to support the development of suitable tools. -Chapter 3 proposes a conceptual model that specifies the various enviromnental aspects that are relevant for strategic decision making, how they relate to each other, and ,defines them in a more formal way that is more suited for information systems development. -Chapter 4 is dedicated to the evaluation of the proposed model on the basis of its application to a concrete environment to evaluate its suitability to describe the current conditions and potential evolution of a real environment and get an idea of its usefulness. -Chapter 5 goes a step further by assembling a toolbox describing a set of methods that can be used to analyze the various environmental aspects put forward by the model and by providing more detailed specifications for a number of them to show how our model can be used to facilitate their implementation as software tools. -Chapter 6 describes a prototype of a strategic decision support tool that allow the analysis of some of the aspects of the environment that are not well supported by existing tools and namely to analyze the relationship between multiple actors and issues. The usefulness of this prototype is evaluated on the basis of its application to a concrete environment. -Chapter 7 finally concludes this thesis by making a summary of its various contributions and by proposing further interesting research directions.

Current status and perspectives of cell therapy in Chagas disease

One century after its discovery, Chagas disease, caused by the protozoan, Trypanosoma cruzi, remains a major health problem in Latin America. Mortality and morbidity are mainly due to chronic processes that lead to dysfunction of the cardiac and digestive systems. About one third of the chronic chagasic individuals have or will develop the symptomatic forms of the disease, with cardiomyopathy being the most common chronic form. This is a progressively debilitating disease for which there are no currently available effective treatments other than heart transplantation. Like in other cardiac diseases, tissue engineering and cell therapy have been investigated in the past few years as a means of recovering the heart function lost as a consequence of chronic damage caused by the immune-mediated pathogenic mechanisms elicited in individuals with chronic chagasic cardiomyopathy. Here we review the studies of cell therapy in animal models and patients with chronic Chagas disease and the perspectives of the recovery of the heart function lost due to infection with T. cruzi.

Evidence evaluation in fingerprint comparison and automated fingerprint identification systems: modeling between finger variability

In the context of the investigation of the use of automated fingerprint identification systems (AFIS) for the evaluation of fingerprint evidence, the current study presents investigations into the variability of scores from an AFIS system when fingermarks from a known donor are compared to fingerprints that are not from the same source. The ultimate goal is to propose a model, based on likelihood ratios, which allows the evaluation of mark-to-print comparisons. In particular, this model, through its use of AFIS technology, benefits from the possibility of using a large amount of data, as well as from an already built-in proximity measure, the AFIS score. More precisely, the numerator of the LR is obtained from scores issued from comparisons between impressions from the same source and showing the same minutia configuration. The denominator of the LR is obtained by extracting scores from comparisons of the questioned mark with a database of non-matching sources. This paper focuses solely on the assignment of the denominator of the LR. We refer to it by the generic term of between-finger variability. The issues addressed in this paper in relation to between-finger variability are the required sample size, the influence of the finger number and general pattern, as well as that of the number of minutiae included and their configuration on a given finger. Results show that reliable estimation of between-finger variability is feasible with 10,000 scores. These scores should come from the appropriate finger number/general pattern combination as defined by the mark. Furthermore, strategies of obtaining between-finger variability when these elements cannot be conclusively seen on the mark (and its position with respect to other marks for finger number) have been presented. These results immediately allow case-by-case estimation of the between-finger variability in an operational setting.

Unusual voltage sag event detection in power systems

Three multivariate statistical tools (principal component analysis, factor analysis, analysis discriminant) have been tested to characterize and model the sags registered in distribution substations. Those models use several features to represent the magnitude, duration and unbalanced grade of sags. They have been obtained from voltage and current waveforms. The techniques are tested and compared using 69 registers of sags. The advantages and drawbacks of each technique are listed

Estimation of zero-sequence impedance of undergrounds cables for single-phase fault location in distribution systems with electric arc

This paper focus on the problem of locating single-phase faults in mixed distribution electric systems, with overhead lines and underground cables, using voltage and current measurements at the sending-end and sequence model of the network. Since calculating series impedance for underground cables is not as simple as in the case of overhead lines, the paper proposes a methodology to obtain an estimation of zero-sequence impedance of underground cables starting from previous single-faults occurred in the system, in which an electric arc occurred at the fault location. For this reason, the signal is previously pretreated to eliminate its peaks voltage and the analysis can be done working with a signal as close as a sinus wave as possible

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach.

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice.

Eddy current effects on a clinical 7T-68 cm bore scanner.

INTRODUCTION: Eddy currents induced by switching of magnetic field gradients can lead to distortions in short echo-time spectroscopy or diffusion weighted imaging. In small bore magnets, such as human head-only systems, minimization of eddy current effects is more demanding because of the proximity of the gradient coil to conducting structures. METHODS: In the present study, the eddy current behavior achievable on a recently installed 7 tesla-68 cm bore head-only magnet was characterized. RESULTS: Residual effects after compensation were shown to be on the same order of magnitude as those measured on two whole body systems (3 and 4.7 T), while using two to three fold increased gradient slewrates.

Determine Initial Cause for Current Premature Portland Cement Concrete Pavement Deterioration Final Report, 2000

A detailed investigation has been conducted on core samples taken from 17 portland cement concrete pavements located in Iowa. The goal of the investigation was to help to clarify the root cause of the premature deterioration problem that has become evident since the early 1990s. Laboratory experiments were also conducted to evaluate how cement composition, mixing time, and admixtures could have influenced the occurrence of premature deterioration. The cements used in this study were selected in an attempt to cover the main compositional parameters pertinent to the construction industry in Iowa. The hardened air content determinations conducted during this study indicated that the pavements that exhibited premature deterioration often contained poor to marginal entrained-air void systems. In addition, petrographic studies indicated that sometimes the entrained-air void system had been marginal after mixing and placement of the pavement slab, while in other instances a marginal to adequate entrained-air void system had been filled with ettringite. The filling was most probably accelerated because of shrinkage cracking at the surface of the concrete pavements. The results of this study suggest that the durability—more sciecifically, the frost resistance—of the concrete pavements should be less than anticipated during the design stage of the pavements. Construction practices played a significant role in the premature deterioration problem. The pavements that exhibited premature distress also exhibited features that suggested poor mixing and poor control of aggregate grading. Segregation was very common in the cores extracted from the pavements that exhibited premature distress. This suggests that the vibrators on the paver were used to overcome a workability problem. Entrained-air voids formed in concrete mixtures experiencing these types of problems normally tend to be extremely coarse, and hence they can easily be lost during the paving process. This tends to leave the pavement with a low air content and a poor distribution of air voids. All of these features were consistent with a premature stiffening problem that drastically influenced the ability of the contractor to place the concrete mixture. Laboratory studies conducted during this project indicated that most premature stiffening problems can be directly attributed to the portland cement used on the project. The admixtures (class C fly ash and water reducer) tended to have only a minor influence on the premature stiffening problem when they were used at the dosage rates described in this study.

Transmit diversity vs. spatial multiplexing in modern MIMO systems

A contemporary perspective on the tradeoff between transmit antenna diversity andspatial multiplexing is provided. It is argued that, in the context of most modern wirelesssystems and for the operating points of interest, transmission techniques that utilizeall available spatial degrees of freedom for multiplexing outperform techniques that explicitlysacrifice spatial multiplexing for diversity. In the context of such systems, therefore,there essentially is no decision to be made between transmit antenna diversity and spatialmultiplexing in MIMO communication. Reaching this conclusion, however, requires thatthe channel and some key system features be adequately modeled and that suitable performancemetrics be adopted; failure to do so may bring about starkly different conclusions. Asa specific example, this contrast is illustrated using the 3GPP Long-Term Evolution systemdesign.

Long-Range Goals for Iowa's Criminal& Junvenile Justice Systems, 2005

The attached plan builds upon work done over the last decade. The first plan developed after the creation of the Division of Criminal and Juvenile Justice Planning in 1986 was issued in 1990 and annually updated through 1994. Since 1992, the CJJPAC has been required to coordinate their planning activities with those of the Iowa Juvenile Justice Advisory Council (JJAC). In 1995, these two councils developed a new plan consisting of a set of long-range justice system goals to assist policy makers and justice system practitioners as they plan and operate the justice system through the next twenty years. The statutory mandate for such long-range planning required the identification of goals specific enough to provide guidance, but broad enough to be of relevance over a long period of time. The long-range goals adopted by these councils in 1995 covered a wide variety of topics and offered a framework within which current practices could be defined and assessed. Collectively, these long-range goals were meant to provide a single source of direction to the complex assortment of practitioners and policymakers whose individual concerns and decisions collectively define the nature and effectiveness of Iowa’s justice system. The twenty-year goals established in 1995 were reviewed by the councils in 2000 to assess their current relevance. It was determined that, with a few revisions, the goals established in 1995 should be restated in 2000 with a renewed emphasis on their long-range status. This plan builds upon those issued in 1995 and 2000, continuing much of the emphasis of plans, with some new directions charted as appropriate.

Sequential estimation of time-varying multipath channel for MIMO-OFDM systems

In this paper, we introduce a pilot-aided multipath channel estimator for Multiple-Input Multiple-Output (MIMO) Orthogonal Frequency Division Multiplexing (OFDM) systems. Typical estimation algorithms assume the number of multipath components and delays to be known and constant, while theiramplitudes may vary in time. In this work, we focus on the more realistic assumption that also the number of channel taps is unknown and time-varying. The estimation problem arising from this assumption is solved using Random Set Theory (RST), which is a probability theory of finite sets. Due to the lack of a closed form of the optimal filter, a Rao-Blackwellized Particle Filter (RBPF) implementation of the channel estimator is derived. Simulation results demonstrate the estimator effectiveness.