Design and evaluation of a panel os single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering approximately 1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.

Optimum power allocation for parallel Gaussian channels with arbitrary input distributions

The mutual information of independent parallel Gaussian-noise channels is maximized, under an average power constraint, by independent Gaussian inputs whose power is allocated according to the waterfilling policy. In practice, discrete signalling constellations with limited peak-to-average ratios (m-PSK, m-QAM, etc) are used in lieu of the ideal Gaussian signals. This paper gives the power allocation policy that maximizes the mutual information over parallel channels with arbitrary input distributions. Such policy admits a graphical interpretation, referred to as mercury/waterfilling, which generalizes the waterfilling solution and allows retaining some of its intuition. The relationship between mutual information of Gaussian channels and nonlinear minimum mean-square error proves key to solving the power allocation problem.

On the Segregation of Genetically Modified, Conventional, and Organic Products in European Agriculture: A Multi-market Equilibrium Analysis, October 2005

Evaluating the possible benefits of the introduction of genetically modified (GM) crops must address the issue of consumer resistance as well as the complex regulation that has ensued. In the European Union (EU) this regulation envisions the “co-existence” of GM food with conventional and quality-enhanced products, mandates the labelling and traceability of GM products, and allows only a stringent adventitious presence of GM content in other products. All these elements are brought together within a partial equilibrium model of the EU agricultural food sector. The model comprises conventional, GM and organic food. Demand is modelled in a novel fashion, whereby organic and conventional products are treated as horizontally differentiated but GM products are vertically differentiated (weakly inferior) relative to conventional ones. Supply accounts explicitly for the land constraint at the sector level and for the need for additional resources to produce organic food. Model calibration and simulation allow insights into the qualitative and quantitative effects of the large-scale introduction of GM products in the EU market. We find that the introduction of GM food reduces overall EU welfare, mostly because of the associated need for costly segregation of non-GM products, but the producers of quality-enhanced products actually benefit.

BIMS: Biomedical Information Management System

This final year project presents the design principles and prototype implementation of BIMS (Biomedical Information Management System), a flexible software system which provides an infrastructure to manage all information required by biomedical research projects.The BIMS project was initiated with the motivation to solve several limitations in medical data acquisition of some research projects, in which Universitat Pompeu Fabra takes part. These limitations,based on the lack of control mechanisms to constraint information submitted by clinicians, impact on the data quality, decreasing it.BIMS can easily be adapted to manage information of a wide variety of clinical studies, not being limited to a given clinical specialty. The software can manage both, textual information, like clinical data (measurements, demographics, diagnostics, etc ...), as well as several kinds of medical images (magnetic resonance imaging, computed tomography, etc ...). Moreover, BIMS provides a web - based graphical user interface and is designed to be deployed in a distributed andmultiuser environment. It is built on top of open source software products and frameworks.Specifically, BIMS has been used to represent all clinical data being currently used within the CardioLab platform (an ongoing project managed by Universitat Pompeu Fabra), demonstratingthat it is a solid software system, which could fulfill requirements of a real production environment.

Financing Constraints, Irreversibility, and Investment Dynamics

We develop a model of an industry with many heterogeneous firms that face both financing constraints and irreversibility constraints. The financing constraint implies that firms cannot borrow unless the debt is secured by collateral; the irreversibility constraint that they can only sell their fixed capital by selling their business. We use this model to examine the cyclical behavior of aggregate fixed investment, variable capital investment, and output in the presence of persistent idiosyncratic and aggregate shocks. Our model yields three main results. First, the effect of the irreversibility constraint on fixed capital investment is reinforced by the financing constraint. Second, the effect of the financing constraint on variable capital investment is reinforced by the irreversibility constraint. Finally, the interaction between the two constraints is key for explaining why input inventories and material deliveries of US manufacturing firms are so volatile and procyclical, and also why they are highly asymmetrical over the business cycle.

Adverse selection, credit, and efficiency: the case of the missing market

We analyze a standard environment of adverse selection in credit markets. In our environment, entrepreneurs who are privately informed about the quality of their projects need to borrow in order to invest. Conventional wisdom says that, in this class of economies, the competitive equilibrium is typically inefficient. We show that this conventional wisdom rests on one implicit assumption: entrepreneurs can only access monitored lending. If a new set of markets is added to provide entrepreneurs with additional funds, efficiency can be attained in equilibrium. An important characteristic of these additional markets is that lending in them must be unmonitored, in the sense that it does not condition total borrowing or investment by entrepreneurs. This makes it possible to attain efficiency by pooling all entrepreneurs in the new markets while separating them in the markets for monitored loans.

The Sustainable Debts of Philip II: A Reconstruction of Spain's Fiscal Position, 1560-1598

The defaults of Philip II have attained mythical status as the origin of sovereign debt crises. Four times during his reign the king failed to honor his debts and had to renegotiate borrowing contracts. In this paper, we reassess the fiscal position of Habsburg Spain. New archival evidence allows us to derive comprehensive estimates of debt and revenue. These show that primary surpluses were sufficient to make the king's debt sustainable in most scenarios. Spain's debt burden was manageable up to the 1580s, and its fiscal position only deteriorated for good after the defeat of the "Invincible Armada." We also estimate fiscal policy reaction functions, and show that Spain under the Habsburgs was at least as "responsible" as the US in the 20th century or as Britain in the 18th century. Our results suggest that the outcome of uncertain events such as wars may influence on a history of default more than strict adherence to fiscal rules.

Credit Constraints, Firms' Precautionary Investment, and the Business Cycle

This paper studies the macroeconomic implications of firms' precautionary investment behavior in response to the anticipation of future financing constraints. Firms increase their demand for liquid and safe investments in order to alleviate future borrowing constraints and decrease the probability of having to forego future profitable investment opportunities. This results in an increase in the share of short-term projects that produces a temporary increase in output, at the expense of lower long-run investment and future output. I show in a calibrated model that this behavior is at the source of a novel and powerful channel of shock transmission of productivity shocks that produces short-run dampening and long-run propagation. Furthermore, it can account for the observed business cycle patterns of the aggregate and firm-level composition of investment.

Institutions, Public Debt and Foreign Finance

We study the role of domestic financial institutions in sustaining capital flows to the private and public sector of a country whose government can default on its debt. As in recent public debt crises, in our model public defaults weaken banks' balance sheets, disrupting domestic financial markets. This effect leads to a novel complementarity between private capital inflows and public borrowing, where the former sustain the latter by boosting the government's cost of default. Our key message is that, by shaping the direction of private capital flows, financial institutions determine whether financial integration improves or reduces government discipline. We explore the implications of this complementarity for financial liberalization and debt-financed bailouts of banks. We present some evidence consistent with complementarity.

Trait decoupling promotes evolutionary diversification of the trophic and acoustic system of damselfishes.

Trait decoupling, wherein evolutionary release of constraints permits specialization of formerly integrated structures, represents a major conceptual framework for interpreting patterns of organismal diversity. However, few empirical tests of this hypothesis exist. A central prediction, that the tempo of morphological evolution and ecological diversification should increase following decoupling events, remains inadequately tested. In damselfishes (Pomacentridae), a ceratomandibular ligament links the hyoid bar and lower jaws, coupling two main morphofunctional units directly involved in both feeding and sound production. Here, we test the decoupling hypothesis by examining the evolutionary consequences of the loss of the ceratomandibular ligament in multiple damselfish lineages. As predicted, we find that rates of morphological evolution of trophic structures increased following the loss of the ligament. However, this increase in evolutionary rate is not associated with an increase in trophic breadth, but rather with morphofunctional specialization for the capture of zooplanktonic prey. Lineages lacking the ceratomandibular ligament also shows different acoustic signals (i.e. higher variation of pulse periods) from others, resulting in an increase of the acoustic diversity across the family. Our results support the idea that trait decoupling can increase morphological and behavioural diversity through increased specialization rather than the generation of novel ecotypes.

The representations of adolescents about gynecological consultation

Objective: To analyze the social representation of adolescents about gynecological consultation and the influence of those in searching for consultations. Method: Qualitative descriptive study based on the Social Representations Theory, conducted with 50 adolescents in their last year of middle school. The data was collected between April and May of 2010 by Evocations and a Focal Group. The software EVOC and contextual analysis were used in the data treatment. Results: The elements fear and constraint, constant in the central nucleus, can justify the low frequency of adolescents in consultations. The term embarrassment in the peripheral system reinforce current sociocultural norms, while prevention, associated with learning about sex and clarifying doubts, allows to envision an educative function. Obtained testimonies in the focal groups exemplify and reinforce those findings. Conclusion: For an effective health education, professionals, including nurses, need to clarify the youth individually and collectively about their rights to privacy, secrecy, in addition to focus the gynecological consultation as a promotion measure to sexual and reproductive health.

Segmental copy number variation shapes tissue transcriptomes.

Copy number variation (CNV) is a key source of genetic diversity, but a comprehensive understanding of its phenotypic effect is only beginning to emerge. We have generated a CNV map in wild mice and classical inbred strains. Genome-wide expression data from six major organs show not only that expression of genes within CNVs tend to correlate with copy number changes, but also that CNVs influence the expression of genes in their vicinity, an effect that extends up to half a megabase. Genes within CNVs show lower expression and more specific spatial expression patterns than genes mapping elsewhere. Our analyses reveal differential constraint on copy number changes of genes expressed in different tissues. Dosage alterations of brain-expressed genes are less frequent than those of other genes and are buffered by tighter transcriptional regulation. Our study provides initial evidence that CNVs shape tissue transcriptomes on a global scale.

Aplicação da Teoria dos Constrangimentos ao Sector de Transporte Público Colectivo – O Caso Da Transcor-Sv, S.A. –

Com a necessidade de adaptação às crescentes mudanças no mundo dos negócios, ao longo dos últimos anos a contabilidade de gestão tem sido criticada, pois os métodos de custeio tradicionalmente utilizados, não estão acompanhando estas mudanças, incapacitando a utilização destes como instrumentos de gestão eficazes. Na busca de ferramentas de gestão para auxiliar na tomada de decisão, foi desenvolvida a Teoria dos Constrangimentos (TOC) ou das Restrições, uma ferramenta de gestão cuja premissa é a identificação de constrangimentos que limitem a capacidade da empresa no alcance da sua meta. Muito se tem escrito sobre a aplicação desta teoria em empresas industriais, uma vez que, nessas organizações a existência de constrangimentos está mais presente. Tendo como objectivo verificar a viabilidade de aplicação desta teoria na actividade de prestação de serviços, o presente trabalho refere-se ao estudo de caso numa empresa de prestação de serviço de transporte público colectivo de passageiros TRANSCOR-SV,S.A., localizada na ilha de São Vicente. Para tal, identificámos factores considerados constrangimentos nos sistemas de transporte colectivo, através da aplicação de um questionário. Com estes factores em mãos, aplicámos a metodologia baseada no Processo de Raciocínio (PR) da OC. With the need of adaption to the growing changes happening in the business world, throughout the last few years, management accounting has been much criticized for the methods of costing used are not following such changes, turning the use of these meth-ods powerless to help provide an effective management in companies. In the search for creating useful tools to help guarantee effectiveness in decision making in companies, the Constraint Theory, or Restriction Theory, was created as a management tool in which the fundamental objective is to identify constraints that limit the capacity of a company to reach its goals successfully. Much has been written about the application of this theory in corporate industries, once in such business the existence of constraints is very present. With the aim of verifying the viability of its use in service rendered in collective public transport, this work is characterized by the case study of one such company in São Vicente. Initially, some factors that can be seen as constraints were identified in the public transport service, through the use of a questionnaire. With the results, follows the employ of the Thinking Process methodology in the analysis based in the Theory of Constraint.

Equilibrium asset prices and savings of heterogeneous agents in the presence of incomplete markets and portfolio constraints

We study the quantitative properties of a dynamic general equilibrium model in which agents face both idiosyncratic and aggregate income risk, state-dependent borrowing constraints that bind in some but not all periods and markets are incomplete. Optimal individual consumption-savings plans and equilibrium asset prices are computed under various assumptions about income uncertainty. Then we investigate whether our general equilibrium model with incomplete markets replicates two empirical observations: the high correlation between individual consumption and individual income, and the equity premium puzzle. We find that, when the driving processes are calibrated according to the data from wage income in different sectors of the US economy, the results move in the direction of explaining these observations, but the model falls short of explaining the observed correlations quantitatively. If the incomes of agents are assumed independent of each other, the observations can be explained quantitatively.

Globalization and risk sharing

We study the effects of globalization on risk sharing and welfare. Like previous literature, weassume that countries cannot commit to repay their debts. Unlike previous literature, we assumethat countries cannot discriminate between domestic and foreign creditors when repaying theirdebts. This creates novel interactions between domestic and international trade in assets. (i)Increases in domestic trade raise the bene.ts of enforcement and facilitate international trade.In fact, in our setup countries can obtain international risk sharing even in the absence of defaultpenalties. (ii) Increases in foreign trade .i.e. globalization.raise the costs of enforcement andhamper domestic trade. As a result, globalization may worsen domestic risk sharing and lowerwelfare. We show how these e¤ects depend on various characteristics of tradable goods andexplore the roles of borrowing limits, debt renegotiations, and trade policy.