191 research outputs found

    A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes

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    It is well known that, under suitable conditions, microRNAs are able to fine tune the relative concentration of their targets to any desired value. We show that this function is particularly effective when one of the targets is a Transcription Factor (TF) which regulates the other targets. This combination defines a new class of feed-forward loops (FFLs) in which the microRNA plays the role of master regulator. Using both deterministic and stochastic equations we show that these FFLs are indeed able not only to fine-tune the TF/target ratio to any desired value as a function of the miRNA concentration but also, thanks to the peculiar topology of the circuit, to ensures the stability of this ratio against stochastic fluctuations. These two effects are due to the interplay between the direct transcriptional regulation and the indirect TF/Target interaction due to competition of TF and target for miRNA binding (the so called "sponge effect"). We then perform a genome wide search of these FFLs in the human regulatory network and show that they are characterizedby a very peculiar enrichment pattern. In particular they are strongly enriched in all the situations in which the TF and its target have to be precisely kept at the same concentration notwithstanding the environmental noise. As an example we discuss the FFL involving E2F1 as Transcription Factor, RB1 as target and miR-17 family as master regulator. These FFLs ensure a tight control of the E2F/RB ratio which in turns ensures the stability of the transition from the G0/G1 to the S phase in quiescent cells.Comment: 23 pages, 10 figure

    Actuació d'un veterinari clínic davant d'un animal exòtic il·legal a la consulta

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    Treball presentat a la Facultat de Veterinària de la Universitat Autònoma de Barcelona.Treball presentat a l'assignatura de Deontologia i Veterinària Legal (21223

    #UABREFUGI : la Universitat en la defensa dels drets de les persones migrants i refugiades

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    Integració de diferents fonts de dades òmiques i visualització de les variables originals mitjançant tècniques de Machine Learning

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    Treballs Finals de Grau en Estadística UB-UPC, Facultat d'Economia i Empresa (UB) i Facultat de Matemàtiques i Estadística (UPC), Curs: 2013-2014, Tutor: Esteban Vegas LozanoEn l’última dècada s’han desenvolupat noves tecnologies d’alt rendiment, les quals generen un volum de dades biològiques tan gran que ha motivat la creació de nous algorismes en el camp de la bioinformàtica per analitzar les dades generades. Aquests avenços han revolucionat la biologia molecular i han conduït a una nova mentalitat en la qual es desenvolupa una visió global dels sistemes biològics. En aquest context, actualment hi ha dues grans vies d’investigació: la integració de dades òmiques i la visualització de les variables originals. L’anàlisi de dades òmiques de més d’un tipus de forma simultània combinada amb la visualització de les relacions entre els milers de variables biològiques pot portar a una millor comprensió dels processos biològics. En aquest projecte s’estudia la tècnica del Kernel PCA juntament amb procediments per a representar les variables originals, s’aplica a dos conjunts de dades òmiques i es presenta de forma accessible amb aplicacions web interactives.The development in the last decade of the high-throughput technologies, new techniques for measuring biological data, has dramatically changed our views on molecular biology. Whereas a few years ago each gene or protein was studied as a single entity, new technologies allow to analyse large numbers of genes or proteins simultaneously. As a result, biological processes are studied as complex systems of functionally interacting macromolecules. This new mindset has led to the rise of new disciplines, such as genomics, proteomics and transcriptomics, in the so-called “omics era”. All of them have in common that are based on the analysis of a large volume of heterogeneous biological data. These datasets encourage researchers to develop new algorithms in the field of bioinformatics for its interpretation. Within this context, there are currently two major research challenges: omics data integration and visualization of the input variables. The analysis at the same time of integrated omics data combined with the visualization of relationships between the thousands of biological variables generated may lead to a better understanding of the global functioning of biological systems. Although individual analysis of each of these omics data undoubtedly results into interesting findings, it is only by integrating them that one can gain a global insight into cellular behavior. A systems approach thus is predicated on the integration of multiple independent datasets. Visualization is a key aspect of both the analysis and understanding of the omics data. The challenge is to create clear and meaningful visualizations that give biological insight, despite the complexity of the data. In this project, first we present the main types of omics data, the associated highthroughput technologies and the challenges that present its analysis, including the integration of omics data. After this, we give an overview of the discipline of machine learning, which provides algorithms and techniques to analyze omics data. In addition, special attention is paid to kernel methods, which are one of the most powerful methods for integrating heterogeneous data types. In the present work, we analyze the integration of data from several sources of information using the Kernel PCA technique together with a set of procedures to represent the input variables. Then we apply them to two different omics datasets. In addition, we provide this technique in an accessible way by the creation of interactive web applications

    Transició energètica i canvi de paradigma

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    Immersed in a process of continuous growth, a large part of the population is unaware or even denies the energy crisis or believes that it is strictly a technical issue. Faced with the decline of fossil fuels, which still today represent 80% of the energy system, and the serious climatic repercussions, pollution and destruction of ecosystems that their use entails, it is necessary to move towards clean and renewable energy sources. Unlike fossil fuels, renewable energy resources are evenly distributed, and therefore accessible to all humankind. This paper argues that a paradigm shift in energy and natural resources use is necessary to make possible an energy transition that avoids collapse. This shift must consider the following key aspects: 1) Recognition of the finiteness of natural resources, abandoning the perspective of perpetual growth; 2) Focusing of attention on specific energy needs, looking upstream for the most favourable path and renewable sources, and 3) Involvement of all citizens in the procurement, appropriate uses and management of energy and resources.Keywords: energy transition, renewable energies, paradigm shift.Immersos en un procés de creixement continu, una gran part de la població desconeix o nega la crisi energètica, o bé creu que es tracta d’un problema estrictament tècnic. Davant del declivi dels combustibles fòssils, que avui dia encara alimenten el 80 % del sistema energètic, i de les greus repercussions climàtiques, de contaminació i de destrucció d’ecosistemes que comporta el seu ús, cal transitar vers fonts energètiques netes i renovables. A diferència dels combustibles fòssils, es tracta de fonts energètiques totalment distribuïdes i, per tant, d’accés transversal a tota la humanitat. Aquest article argumenta que cal un canvi de paradigma sobre l’energia i els recursos naturals per a fer possible una transició energètica que eviti el col·lapse. Aquest canvi ha d’incloure els aspectes clau següents: 1) ha de reconèixer la finitud dels recursos naturals, tot abandonant la perspectiva del creixement continu; 2) ha de centrar l’atenció en les necessitats energètiques concretes i cercar aigües amunt el camí i les fonts renovables més favorables, i 3) ha d’implicar tota la ciutadania en l’obtenció, els usos adequats i la gestió de l’energia i dels recursos.Paraules clau: transició energètica, energies renovables, canvi de paradigma

    Testing the length limit of loop grafting in a helical repeat protein.

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    Alpha-helical repeat proteins such as consensus-designed tetratricopeptide repeats (CTPRs) are exceptionally stable molecules that are able to tolerate destabilizing sequence alterations and are therefore becoming increasingly valued as a modular platform for biotechnology and biotherapeutic applications. A simple approach to functionalize the CTPR scaffold that we are pioneering is the insertion of short linear motifs (SLiMs) into the loops between adjacent repeats. Here, we test the limits of the scaffold by inserting 17 highly diverse amino acid sequences of up to 58 amino acids in length into a two-repeat protein and examine the impact on protein folding, stability and solubility. The sequences include three SLiMs that bind oncoproteins and eleven naturally occurring linker sequences all predicted to be intrinsically disordered but with conformational preferences ranging from compact globules to expanded coils. We show that the loop-grafted proteins retain the native CTPR structure and are thermally stable with melting temperatures above 60 ​°C, despite the longest loop sequence being almost the same size as the CTPR scaffold itself (68 amino acids). Although the main determinant of the effect of stability was found to be loop length and was relatively insensitive to amino acid composition, the relationship between protein solubility and the loop sequences was more complex, with the presence of negatively charged amino acids enhancing the solubility. Our findings will help us to fully realize the potential of the repeat-protein scaffold, allowing a rational design approach to create artificial modular proteins with customized functional capabilities

    Estrategias para aumentar la tasa de respuesta y los resultados de la Encuesta Social Europea en España

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    The longitudinal analysis of the contact form data of the third round of the European Social Survey in Spain allows us to identify the most successful strategies in order to increase response rates in social and political surveys in Spain. The analysis of these data provides us with very useful information to estimate what are the likely gains in response rate due to the improvements of fieldwork design and supervision. More especially, we show in this paper that concentrating fieldwork efforts in locating and converting refusals with specific strategies such as a better controlling of interviewers, increasing incentives, and targeting respondents after the regular working hours and during weekends really pay off.El análisis de los datos de la tercera ola de la Encuesta Social Europea en España y su comparación con los de las dos olas precedentes permiten descubrir los factores que más han incidido en la mejora de los resultados y cuál es el perfil de las personas sobre las que es más rentable concentrar los esfuerzos de localización y de conversión de negativas, siendo las localizaciones y las conversiones las que, en definitiva, han constituido las principales claves del éxito. El trabajo muestra que el aumento de la tasa de respuesta de la tercera ola con respecto de las dos olas precedentes fue debido esencialmente a un mayor y mejor control de los procesos de campo, a un incremento de los incentivos a los entrevistadores y a un mayor esfuerzo de localización y conversión de negativas en horarios fuera de la jornada laboral habitual
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