A role for Yin Yang-1 (YY1) in the assembly of snRNA transcription complexes.

The RNA polymerase (pol) II and III human small nuclear RNA (snRNA) genes have very similar promoters and recruit a number of common factors. In particular, both types of promoters utilize the small nuclear RNA activating protein complex (SNAP(c)) and the TATA box binding protein (TBP) for basal transcription, and are activated by Oct-1. We find that SNAP(c) purified from cell lines expressing tagged SNAP(c) subunits is associated with Yin Yang-1 (YY1), a factor implicated in both activation and repression of transcription. Recombinant YY1 accelerates the binding of SNAP(c) to the proximal sequence element, its target within snRNA promoters. Moreover, it enhances the formation of a complex on the pol III U6 snRNA promoter containing all the factors (SNAP(c), TBP, TFIIB-related factor 2 (Brf2), and B double prime 1 (Bdp1)) that are sufficient to direct in vitro U6 transcription when complemented with purified pol III, as well as that of a subcomplex containing TBP, Brf2, and Bdp1. YY1 is found on both the RNA polymerase II U1 and the RNA polymerase III U6 promoters as determined by chromatin immunoprecipitations. Thus, YY1 represents a new factor that participates in transcription complexes formed on both pol II and III promoters.

Costly search and design

Firms compete by choosing both a price and a design from a family of designs thatcan be represented as demand rotations. Consumers engage in costly sequential searchamong firms. Each time a consumer pays a search cost he observes a new offering. Anoffering consists of a price quote and a new good, where goods might vary in the extentto which they are good matches for the consumer. In equilibrium, only two design-styles arise: either the most niche where consumers are likely to either love or loathethe product, or the broadest where consumers are likely to have similar valuations. Inequilibrium, different firms may simultaneously offer both design-styles. We performcomparative statics on the equilibrium and show that a fall in search costs can lead tohigher industry prices and profits and lower consumer surplus. Our analysis is relatedto discussions of how the internet has led to the prevalence of niche goods and the"long tail" phenomenon.

The minimax distortion redundancy in empirical quantizer design

We obtain minimax lower and upper bounds for the expected distortionredundancy of empirically designed vector quantizers. We show that the meansquared distortion of a vector quantizer designed from $n$ i.i.d. datapoints using any design algorithm is at least $\Omega (n^{-1/2})$ awayfrom the optimal distortion for some distribution on a bounded subset of${\cal R}^d$. Together with existing upper bounds this result shows thatthe minimax distortion redundancy for empirical quantizer design, as afunction of the size of the training data, is asymptotically on the orderof $n^{1/2}$. We also derive a new upper bound for the performance of theempirically optimal quantizer.

The challenge of representative design in psychology and economics

The demands of representative design, as formulated by Egon Brunswik (1956), set a high methodological standard. Both experimental participants and the situations with which they are faced should be representative of the populations to which researchers claim to generalize results. Failure to observe the latter has led to notable experimental failures in psychology from which economics could learn. It also raises questions about the meaning of testing economic theories in abstract environments. Logically, abstract tests can only be generalized to abstract realities and these may or may not have anything to do with the empirical realities experienced by economic actors.

Expanding molecular modeling and design tools to non-natural sidechains.

Protein-protein interactions encode the wiring diagram of cellular signaling pathways and their deregulations underlie a variety of diseases, such as cancer. Inhibiting protein-protein interactions with peptide derivatives is a promising way to develop new biological and therapeutic tools. Here, we develop a general framework to computationally handle hundreds of non-natural amino acid sidechains and predict the effect of inserting them into peptides or proteins. We first generate all structural files (pdb and mol2), as well as parameters and topologies for standard molecular mechanics software (CHARMM and Gromacs). Accurate predictions of rotamer probabilities are provided using a novel combined knowledge and physics based strategy. Non-natural sidechains are useful to increase peptide ligand binding affinity. Our results obtained on non-natural mutants of a BCL9 peptide targeting beta-catenin show very good correlation between predicted and experimental binding free-energies, indicating that such predictions can be used to design new inhibitors. Data generated in this work, as well as PyMOL and UCSF Chimera plug-ins for user-friendly visualization of non-natural sidechains, are all available at http://www.swisssidechain.ch. Our results enable researchers to rapidly and efficiently work with hundreds of non-natural sidechains.

Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

Iowa Department of Transportation Fiscal Year 2008 Report of Savings by Using Video Conferencing Through Iowa Communications Network to the Iowa General Assembly Pursuant to Iowa Code § II 84 Acts and Joint Resolutions Enacted at the 1994 Regular Session of the 75th General Assembly of the State of Iowa Iowa Code §8D.10 Report of Savings by State Agencies

Iowa Code § 8D.10 requires certain state agencies prepare an annual report to the General Assembly certifying the identified savings associated with that state agency’s use of the Iowa Communications Network (ICN). This report covers estimated cost savings related to video conferencing via ICN for the Iowa Department of Transportation (DOT). In FY 2008, the DOT did not conduct any sessions utilizing ICN’s video conferencing system. Therefore, no cost savings were calculated for this report.

2009 Iowa General Assembly Reception Report

Form required by Iowa Code section 68B.22(4)(r) and submitted to the Secretary of the Senate and Chief Clerk of the House following the General Assembly Reception Jan. 28, 2009.

Design effect and interviewer effects: Evidence from the Spanish ESS3-2006 Data

In 2007 the first Quality Enhancement Meeting on sampling in the European SocialSurvey (ESS) took place. The discussion focused on design effects and inteviewereffects in face-to-face interviews. Following the recomendations of this meeting theSpanish ESS team studied the impact of interviewers as a new element in the designeffect in the response s variance using the information of the correspondent SampleDesign Data Files. Hierarchical multilevel and cross-classified multilevel analysis areconducted in order to estimate the amount of responses variation due to PSU and tointerviewers for different questions in the survey. Factor such as the age of theinterviewer, gender, workload, training and experience and respondent characteristicssuch as age, gender, renuance to participate and their possible interactions are alsoincluded in the analysis of some specific questions like trust in politicians and trustin legal system . Some recomendations related to future sampling designs and thecontents of the briefing sessions are derived from this initial research.

The role of phylogeny in the spatial distributions and assembly of mountain plant communities.

A major challenge in community ecology is a thorough understanding of the processes that govern the assembly and composition of communities in time and space. The growing threat of climate change to the vascular plant biodiversity of fragile ecosystems such as mountains has made it equally imperative to develop comprehensive methodologies to provide insights into how communities are assembled. In this perspective, the primary objective of this PhD thesis is to contribute to the theoretical and methodological development of community ecology, by proposing new solutions to better detect the ecological and evolutionary processes that govern community assembly. As phylogenetic trees provide by far, the most advanced tools to integrate the spatial, ecological and evolutionary dynamics of plant communities, they represent the cornerstone on which this work was based. In this thesis, I proposed new solutions to: (i) reveal trends in community assembly on phylogenies, depicted by the transition of signals at the nodes of the different species and lineages responsible for community assembly, (ii) contribute to evidence the importance of evolutionarily labile traits in the distribution of mountain plant species. More precisely, I demonstrated that phylogenetic and functional compositional turnover in plant communities was driven by climate and human land use gradients mostly influenced by evolutionarily labile traits, (iii) predict and spatially project the phylogenetic structure of communities using species distribution models, to identify the potential distribution of phylogenetic diversity, as well as areas of high evolutionary potential along elevation. The altitudinal setting of the Diablerets mountains (Switzerland) provided an appropriate model for this study. The elevation gradient served as a compression of large latitudinal variations similar to a collection of islands within a single area, and allowed investigations on a large number of plant communities. Overall, this thesis highlights that stochastic and deterministic environmental filtering processes mainly influence the phylogenetic structure of plant communities in mountainous areas. Negative density-dependent processes implied through patterns of phylogenetic overdispersion were only detected at the local scale, whereas environmental filtering implied through phylogenetic clustering was observed at both the regional and local scale. Finally, the integration of indices of phylogenetic community ecology with species distribution models revealed the prospects of providing novel and insightful explanations on the potential distribution of phylogenetic biodiversity in high mountain areas. These results generally demonstrate the usefulness of phylogenies in inferring assembly processes, and are worth considering in the theoretical and methodological development of tools to better understand phylogenetic community structure.

O Estereótipo na Publicidade em Cabo verde Estudo de Caso das Publicidades produzidas pela Design Comunicação e Imagem (DECO)

O presente trabalho monográfico intitulado “O estereótipo na publicidade em Cabo Verde – Estudo de Caso das Publicidades Produzida pela Design Comunicação e Imagem”, enquadra-se no âmbito do curso de licenciatura em Ciências da Comunicação, vertente Publicidade realizado pela universidade Jean Piaget de Cabo Verde. O presente trabalho visa apresentar as noções conceptuais do estereótipo e a sua dinâmica na publicidade e argumentar sobre alguns efeitos que este elemento pode promover no discurso publicitário. Assim, propôs-se como estudo de caso as publicidades criadas pela empresa DECO: O objectivo é, essencialmente, caracterizar a publicidade que se faz em Cabo Verde, verificando se os publicitários cabo-verdianos estão a explorar os recursos de que dispõem, designadamente os valores, os estilos de vida, estereótipos, etc., para chegar aos seus consumidores. Com a realização deste trabalho, chegou-se a conclusão que, o estereótipo faz parte da vida do homem para o bem ou para o mal. Sem a sua presença seria muito complicado perceber ou descodificar alguns fenómenos que acontecem na sociedade. O estereótipo ajuda na compreensão de informações que a primeira seria complexo de interpretar, tornando-a fácil.

TIME-21 Funding Analysis A report to the Iowa Legislature, per Section 26, Senate File 2420, 82nd General Assembly

The 82nd General Assembly of the Iowa legislature, in Section 26 of Senate File 2420, required the Iowa Department of Transportation (Iowa DOT) to conduct an analysis of TIME-21 funding. Specifically the legislation requires the following: “The department of transportation shall conduct an analysis of the additional revenues necessary to provide at least two hundred million dollars annually to the TIME-21 fund by FY 2011-2012. The analysis shall include but is not limited to the amount of excise tax levied on motor fuel and adjustments that might be made to various fees collected by the department in order to create an appropriate balance of taxes and fees paid by Iowa drivers and out-of-state drivers. The department shall submit a report to the governor and the general assembly on or before December 31, 2008, regarding its analysis.” As a starting point to this analysis, a reassessment of long-range needs and revenues (including the estimated $200 million most critical annual unmet needs) was made. This was done by assessing changing trends in roadway conditions, revenue and construction costs since the original Study of Iowa’s Current Road Use Tax Funds (RUTF) and Future Road Maintenance and Construction Needs was completed December 2006.

TIME-21 Funding Analysis A report to the Iowa Legislature, per Section 26, Senate File 2420, 82nd General Assembly

The 82nd General Assembly of the Iowa legislature, in Section 26 of Senate File 2420, required the Iowa Department of Transportation (Iowa DOT) to conduct an analysis of TIME-21 funding. Specifically the legislation requires the following: “The department of transportation shall conduct an analysis of the additional revenues necessary to provide at least two hundred million dollars annually to the TIME-21 fund by FY 2011-2012. The analysis shall include but is not limited to the amount of excise tax levied on motor fuel and adjustments that might be made to various fees collected by the department in order to create an appropriate balance of taxes and fees paid by Iowa drivers and out-of-state drivers. The department shall submit a report to the governor and the general assembly on or before December 31, 2008, regarding its analysis.” As a starting point to this analysis, a reassessment of long-range needs and revenues (including the estimated $200 million most critical annual unmet needs) was made. This was done by assessing changing trends in roadway conditions, revenue and construction costs since the original Study of Iowa’s Current Road Use Tax Funds (RUTF) and Future Road Maintenance and Construction Needs was completed December 2006.