Design of new promoters and of a dual-bioreporter based on cross-activation by the two regulatory proteins XylR and HbpR.

The HbpR protein is the sigma54-dependent transcription activator for 2-hydroxybiphenyl degradation in Pseudomonas azelaica. The ability of HbpR and XylR, which share 35% amino acid sequence identity, to cross-activate the PhbpC and Pu promoters was investigated by determining HbpR- or XylR-mediated luciferase expression and by DNA binding assays. XylR measurably activated the PhbpC promoter in the presence of the effector m-xylene, both in Escherichia coli and Pseudomonas putida. HbpR weakly stimulated the Pu promoter in E. coli but not in P. azelaica. Poor HbpR-dependent activation from Pu was caused by a weak binding to the operator region. To create promoters efficiently activated by both regulators, the HbpR binding sites on PhbpC were gradually changed into the XylR binding sites of Pu by site-directed mutagenesis. Inducible luciferase expression from mutated promoters was tested in E. coli on a two plasmid system, and from mono copy gene fusions in P. azelaica and P. putida. Some mutants were efficiently activated by both HbpR and XylR, showing that promoters can be created which are permissive for both regulators. Others achieved a higher XylR-dependent transcription than from Pu itself. Mutants were also obtained which displayed a tenfold lower uninduced expression level by HbpR than the wild-type PhbpC, while keeping the same maximal induction level. On the basis of these results, a dual-responsive bioreporter strain of P. azelaica was created, containing both XylR and HbpR, and activating luciferase expression from the same single promoter independently with m-xylene and 2-hydroxybiphenyl.

Traducción técnica del capítulo III del libro Advanced Data Warehouse design: from conventional to spatial and temporal applications

The proposal to work on this final project came after several discussions held with Dr. Elzbieta Malinowski Gadja, who in 2008 published the book entitled Advanced Data Warehouse Design: From Conventional to Spatial and Temporal Applications (Data-Centric Systems and Applications). The project was carried out under the technical supervision of Dr. Malinowski and the direct beneficiary was the University of Costa Rica (UCR) where Dr. Malinowski is a professor at the Department of Computer Science and Informatics. The purpose of this project was twofold: First, to translate chapter III of said book with the intention of generating educational material for the use of the UCR and, second, to venture in the field of technical translation related to data warehouse. For the first component, the goal was to generate a final product that would eventually serve as an educational tool for the post-graduate courses of the UCR. For the second component, this project allowed me to acquire new skills and put into practice techniques that have helped me not only to perfom better in my current job as an Assistant Translator of the Inter-American BAnk (IDB), but also to use them in similar projects. The process was lenggthy and required torough research and constant communication with the author. The investigation focused on the search of terms and definitions to prepare the glossary, which was the basis to start the translation project. The translation process itself was carried out by phases, so that comments and corrections by the author could be taken into account in subsequent stages. Later, based on the glossary and the translated text, illustrations had been created in the Visio software were translated. In addition to the technical revision by the author, professor Carme Mangiron was in charge of revising the non-technical text. The result was a high-quality document that is currently used as reference and study material by the Department of Computer Science and Informatics of Costa Rica.

The genetic basis of sleep disorders.

The contribution of genes, environment and gene-environment interactions to sleep disorders is increasingly recognized. Well-documented familial and twin sleep disorder studies suggest an important influence of genetic factors. However, only few sleep disorders have an established genetic basis including four rare diseases that may result from a single gene mutation: fatal familial insomnia, familial advanced sleep-phase syndrome, chronic primary insomnia, and narcolepsy with cataplexy. However, most sleep disorders are complex in terms of their genetic susceptibility together with the variable expressivity of the phenotype even within a same family. Recent linkage, genome-wide and candidate gene association studies resulted in the identification of gene mutations, gene localizations, or evidence for susceptibility genes and/or loci in several sleep disorders. Molecular techniques including mainly genome-wide linkage and association studies are further required to identify the contribution of new genes. These identified susceptibility genetic determinants will provide clues to better understand pathogenesis of sleep disorders, to assess the risk for diseases and also to find new drug targets to treat and to prevent the underlying conditions. We reviewed here the role of genetic basis in most of key sleep disorders.

Rational design of indoleamine 2,3-dioxygenase inhibitors.

Indoleamine 2,3-dioxygenase (IDO) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. We have used the evolutionary docking algorithm EADock to design new inhibitors of this enzyme. First, we investigated the modes of binding of all known IDO inhibitors. On the basis of the observed docked conformations, we developed a pharmacophore model, which was then used to devise new compounds to be tested for IDO inhibition. We also used a fragment-based approach to design and to optimize small organic molecule inhibitors. Both approaches yielded several new low-molecular weight inhibitor scaffolds, the most active being of nanomolar potency in an enzymatic assay. Cellular assays confirmed the potential biological relevance of four different scaffolds.

Molecular basis of selective PPARgamma modulation for the treatment of Type 2 diabetes.

Peroxisome proliferator-activated receptors (PPARs) (alpha, beta/delta and gamma) are lipid sensors capable of adapting gene expression to integrate various lipid signals. As such, PPARs are also very important pharmaceutical targets, and specific synthetic ligands exist for the different isotypes and are either currently used or hold promises in the treatment of major metabolic disorders. In particular, compounds of the class of the thiazolinediones (TZDs) are PPARgamma agonists and potent insulin-sensitizers. The specific but still broad expression patterns of PPARgamma, as well as its implication in numerous pathways, constitutes also a disadvantage regarding drug administration, since this potentially increases the chance to generate side-effects through the activation of the receptor in tissues or cells not affected by the disease. Actually, numerous side effects associated with the administration of TZDs have been reported. Today, a new generation of PPARgamma modulators is being actively developed to activate the receptor more specifically, in a cell and time-dependent manner, in order to induce a specific subset of target genes only and modulate a restricted number of metabolic pathways. We will discuss here why and how the development of such selective PPARgamma modulators is possible, and summarize the results obtained with the published molecules.

Safer Construction and Maintenance Safer Construction and Maintenance Practices to Minimize Potential Liability by Counties from Accidents, September 1979

Tort claims resulting from alleged highway defects have introduced an additional element in the planning, design, construction, and maintenance of highways. A survey of county governments in Iowa was undertaken in order to quantify the magnitude and determine the nature of this problem. This survey included the use of mailed questionnaires and personal interviews with County Engineers. Highway-related claims filed against counties in Iowa amounted to about $52,000,000 during the period 1973 through 1978. Over $30,000,000 in claims was pending at the end of 1978. Settlements of judgments were made at a cost of 12.2% of the amount claimed for those claims that had been disposed of, not including costs for handling claims, attorney fees, or court costs. There was no clear time trend in the amount of claims for the six-year period surveyed, although the amount claimed in 1978 was about double the average for the preceding five years. Problems that resulted in claims for damages from counties have generally related to alleged omissions in the use of traffic control devices or defects, often temporary, resulting from alleged inadequacies in highway maintenance. The absence of stop signs or warning signs often has been the central issue in a highway-related tort claim. Maintenance problems most frequently alleged have included inadequate shoulders, surface roughness, ice o? snow conditions, and loose gravel. The variation in the occurrence of tort claims among 85 counties in Iowa could not be related to any of the explanatory variables that were tested. Claims appeared to have occurred randomly. However, using data from a sub sample of 11 counties, a significant relationship was shown probably to exist between the amount of tort claims and the extensiveness of use of warning signs on the respective county road systems. Although there was no indication in any county that their use of warning signs did not conform with provisions of the Manual on Uniform Traffic Control Devices (Federal Highway Administration, Government Printing Office, Washington, D.C., 1978), many more warning signs were used in some counties than would be required to satisfy this minimum requirement. Sign vandalism reportedly is a problem in all counties. The threat of vandalism and the added costs incurred thereby have tended to inhibit more extensive use of traffic control devices. It also should be noted that there is no indication from this research of a correlation between the intensiveness of sign usage and highway safety. All highway maintenance activities introduce some extraordinary hazard for motorists. Generally effective methodologies have evolved for use on county road systems for routine maintenance activities, procedures that tend to reduce the hazard to practical and reasonably acceptable levels. Blading of loose-surfaced roads is an example of such a routine maintenance activity. Alternative patterns for blading that were investigated as part of this research offered no improvements in safety when compared with the method in current use and introduced a significant additional cost that was unacceptable, given the existing limitations in resources available for county roads.

Safer Constrauction and Maintenance Practices to Minimize Potential Liabiliy by Counties from Accidents, Septemeber 1979

Tort claims resulting from alleged highway defects have introduced an additional element in the planning, design, construction, and maintenance of highways. A survey of county governments in Iowa was undertaken in order to quantify the magnitude and determine the nature of this problem. This survey included the use of mailed questionnaires and personal interviews with County Engineers. Highway-related claims filed against counties in Iowa amounted to about $52,000,000 during the period 1973 through 1978. Over $30,000,000 in claims was pending at the end of 1978. Settlements of judgments were made at a cost of 12.2% of the amount claimed for those claims that had been disposed of, not including costs for handling claims, attorney fees, or court costs. There was no clear time trend in the amount of claims for the six-year period surveyed, although the anount claimed in 1978 was about double the average for the preceding five years. Problems that resulted in claims for damages from counties have generally related to alleged omissions in the use of traffic control devices or defects, often temporary, resulting from alleged inadequacies in highway maintenance. The absence of stop signs or warning signs often has been the central issue in a highway-related tort claim. Maintenance problems most frequently alleged have included inadequate shoulders, surface roughness, ice o? snow conditions, and loose gravel. The variation in the occurrence of tort claims among 85 counties in Iowa could not be related to any of the explanatory variables that were tested. Claims hppeared to have occurred randomly. However, using data from a subsample of 11 counties, a significant relationship was shown probably to exist between the amount of tort claims and the extensiveness of use of wcirning signs on the respective county road systems. Although there was no indication in any county that their use of warning signs did not conform with provisions of the Manual on Uniform Traffic Control Devices (Federal Highway Administration, Government Printing Office, Washington, D.C., 1978), many more warning signs were used in some counties than would be required to satisfy this minimum requirement. Sign vandalism reportedly is a problem in all counties. The threat of vandalism and the added costs incurred thereby have tended to inhibit more extensive use of traffic control devices. It also should be noted that there is no indication from this research of a correlation between the intensiveness of sign usage and highway safety. All highway maintenance activities introduce some extraordinary hazard for motorists. Generally effective methodologies have evolved for use on county road systems for routine maintenance activities, procedures that tend to reduce the hazard to practical and reasonably acceptable levels. Blading of loose-surfaced roads is an examples such a routine maintenance activity. Alternative patterns for blading that were investigated as part of this research offered no improvements in safety when compared with the method in current use and introduced a significant additional cost that was unacceptable, given the existing limitations in resources available for county roads.

Visualization Resources for Iowa State University and the Iowa DOT: An Automated Design Model to Simulator Converter, November 2012

The creation of three-dimensional (3D) drawings for proposed designs for construction, re-construction and rehabilitation activities are becoming increasingly common for highway designers, whether by department of transportation (DOT) employees or consulting engineers. However, technical challenges exist that prevent the use of these 3D drawings/models from being used as the basis of interactive simulation. Use of driving simulation to service the needs of the transportation industry in the US lags behind Europe due to several factors, including lack of technical infrastructure at DOTs, cost of maintaining and supporting simulation infrastructure—traditionally done by simulation domain experts—and cost and effort to translate DOT domain data into the simulation domain.

Visualization Resources for Iowa State University and the Iowa DOT: An Automated Design Model to Simulator Converter, November 2012

The creation of three-dimensional (3D) drawings for proposed designs for construction, re-construction and rehabilitation activities are becoming increasingly common for highway designers, whether by department of transportation (DOT) employees or consulting engineers. However, technical challenges exist that prevent the use of these 3D drawings/models from being used as the basis of interactive simulation. Use of driving simulation to service the needs of the transportation industry in the US lags behind Europe due to several factors, including lack of technical infrastructure at DOTs, cost of maintaining and supporting simulation infrastructure—traditionally done by simulation domain experts—and cost and effort to translate DOT domain data into the simulation domain.

Concrete Pavement Mixture Design and Analysis (MDA): Assessment of Air Void System Requirements for Durable Concrete, TPF-5(205), 2012

Concrete will suffer frost damage when saturated and subjected to freezing temperatures. Frost-durable concrete can be produced if a specialized surfactant, also known as an air-entraining admixture (AEA), is added during mixing to stabilize microscopic air voids. Small and well-dispersed air voids are critical to produce frost-resistant concrete. Work completed by Klieger in 1952 found the minimum volume of air required to consistently ensure frost durability in a concrete mixture subjected to rapid freezing and thawing cycles. He suggested that frost durability was provided if 18 percent air was created in the paste. This is the basis of current practice despite the tests being conducted on materials that are no longer available using tests that are different from those in use today. Based on the data presented, it was found that a minimum air content of 3.5 percent in the concrete and 11.0 percent in the paste should yield concrete durable in the ASTM C 666 with modern AEAs and low or no lignosulfonate water reducers (WRs). Limited data suggests that mixtures with a higher dosage of lignosulfonate will need about 1 percent more air in the concrete or 3 percent more air in the paste for the materials and procedures used. A spacing factor of 0.008 in. was still found to be necessary to provide frost durability for the mixtures investigated.

Estimating Design-Flood Discharges for Streams in Iowa Using Drainage-Basin and Channel-Geometry Characteristics, HR-322, 1993

Drainage-basin and channel-geometry multiple-regression equations are presented for estimating design-flood discharges having recurrence intervals of 2, 5, 10, 25, 50, and 100 years at stream sites on rural, unregulated streams in Iowa. Design-flood discharge estimates determined by Pearson Type-III analyses using data collected through the 1990 water year are reported for the 188 streamflow-gaging stations used in either the drainage-basin or channel-geometry regression analyses. Ordinary least-squares multiple-regression techniques were used to identify selected drainage-basin and channel-geometry regions. Weighted least-squares multiple-regression techniques, which account for differences in the variance of flows at different gaging stations and for variable lengths in station records, were used to estimate the regression parameters. Statewide drainage-basin equations were developed from analyses of 164 streamflow-gaging stations. Drainage-basin characteristics were quantified using a geographic-information-system (GIS) procedure to process topographic maps and digital cartographic data. The significant characteristics identified for the drainage-basin equations included contributing drainage area, relative relief, drainage frequency, and 2-year, 24-hour precipitation intensity. The average standard errors of prediction for the drainage-basin equations ranged from 38.6% to 50.2%. The GIS procedure expanded the capability to quantitatively relate drainage-basin characteristics to the magnitude and frequency of floods for stream sites in Iowa and provides a flood-estimation method that is independent of hydrologic regionalization. Statewide and regional channel-geometry regression equations were developed from analyses of 157 streamflow-gaging stations. Channel-geometry characteristics were measured on site and on topographic maps. Statewide and regional channel-geometry regression equations that are dependent on whether a stream has been channelized were developed on the basis of bankfull and active-channel characteristics. The significant channel-geometry characteristics identified for the statewide and regional regression equations included bankfull width and bankfull depth for natural channels unaffected by channelization, and active-channel width for stabilized channels affected by channelization. The average standard errors of prediction ranged from 41.0% to 68.4% for the statewide channel-geometry equations and from 30.3% to 70.0% for the regional channel-geometry equations. Procedures provided for applying the drainage-basin and channel-geometry regression equations depend on whether the design-flood discharge estimate is for a site on an ungaged stream, an ungaged site on a gaged stream, or a gaged site. When both a drainage-basin and a channel-geometry regression-equation estimate are available for a stream site, a procedure is presented for determining a weighted average of the two flood estimates.

Design Methodology for Corrugated Metal Pipe Tiedowns, HR-332, Phase 1, 1993

Questionnaires were sent to transportation agencies in all 50 states in the U.S., to Puerto Rico, and all provinces in Canada asking about their experiences with uplift problems of - corrugated metal pipe (CMP). Responses were received from 52 agencies who reported 9 failures within the last 5 years. Some agencies also provided design standards for tiedowns to resist uplift. There was a wide variety in restraining forces used; for example for a pipe 6 feet in diameter, the resisting force ranged from 10 kips to 66 kips. These responses verified the earlier conclusion based on responses from Iowa county engineers that a potential uplift danger exists.when end restraint is not provided for CMP and that existing designs have an unclear theoretical or experimental basis. In an effort to develop more rational design standards, the longitudinal stiffness of three CMP ranging from 4 to 8 feet in diameter were measured in the laboratory. Because only three tests were conducted, a theoretical model to evaluate the stiffness of pipes of a variety of gages and corrugation geometries was also developed. The experimental results indicated a "stiffness" EI in the range of 9.11 x 10^5 k-in^2 to 34.43 x 10^5 k-in^2 for the three pipes with the larger diameter pipes having greater stiffness. The theoretical model developed conservatively estimates these stiffnesses.

Uncovering the genetic basis of adaptive change: on the intersection of landscape genomics and theoretical population genetics

A workshop recently held at the Ecole Polytechnique Federale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.

The Effect of the No-Passing Zone Sign on "Passing" Accidents, 1963

The No Passing Zone sign (Wl0-4) was designed in 1958 for the purpose of informing the driver contemplating a passing maneuver of hazardous sight conditions ahead. This warning sign, of pennent shape design, was placed on the left side of the road so as to be more conspicuous to the intended driver. During the two year period 1959-1960, the Wl0-4 signs were erected throughout the Iowa Primary Road System.

The business model ontology a proposition in a design science approach

The goal of this dissertation is to find and provide the basis for a managerial tool that allows a firm to easily express its business logic. The methodological basis for this work is design science, where the researcher builds an artifact to solve a specific problem. In this case the aim is to provide an ontology that makes it possible to explicit a firm's business model. In other words, the proposed artifact helps a firm to formally describe its value proposition, its customers, the relationship with them, the necessary intra- and inter-firm infrastructure and its profit model. Such an ontology is relevant because until now there is no model that expresses a company's global business logic from a pure business point of view. Previous models essentially take an organizational or process perspective or cover only parts of a firm's business logic. The four main pillars of the ontology, which are inspired by management science and enterprise- and processmodeling, are product, customer interface, infrastructure and finance. The ontology is validated by case studies, a panel of experts and managers. The dissertation also provides a software prototype to capture a company's business model in an information system. The last part of the thesis consists of a demonstration of the value of the ontology in business strategy and Information Systems (IS) alignment. Structure of this thesis: The dissertation is structured in nine parts: Chapter 1 presents the motivations of this research, the research methodology with which the goals shall be achieved and why this dissertation present a contribution to research. Chapter 2 investigates the origins, the term and the concept of business models. It defines what is meant by business models in this dissertation and how they are situated in the context of the firm. In addition this chapter outlines the possible uses of the business model concept. Chapter 3 gives an overview of the research done in the field of business models and enterprise ontologies. Chapter 4 introduces the major contribution of this dissertation: the business model ontology. In this part of the thesis the elements, attributes and relationships of the ontology are explained and described in detail. Chapter 5 presents a case study of the Montreux Jazz Festival which's business model was captured by applying the structure and concepts of the ontology. In fact, it gives an impression of how a business model description based on the ontology looks like. Chapter 6 shows an instantiation of the ontology into a prototype tool: the Business Model Modelling Language BM2L. This is an XML-based description language that allows to capture and describe the business model of a firm and has a large potential for further applications. Chapter 7 is about the evaluation of the business model ontology. The evaluation builds on literature review, a set of interviews with practitioners and case studies. Chapter 8 gives an outlook on possible future research and applications of the business model ontology. The main areas of interest are alignment of business and information technology IT/information systems IS and business model comparison. Finally, chapter 9 presents some conclusions.