Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains.

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of"emerging" LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage.

Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains.

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of"emerging" LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage.

Asymmetric stochastic switching driven by intrinsic molecular noise

Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

Evolutionary analysis of genetic variants involved in rare diseases

Next-generation sequencing techniques such as exome sequencing can successfully detect all genetic variants in a human exome and it has been useful together with the implementation of variant filters to identify causing-disease mutations. Two filters aremainly used for the mutations identification: low allele frequency and the computational annotation of the genetic variant. Bioinformatic tools to predict the effect of a givenvariant may have errors due to the existing bias in databases and sometimes show a limited coincidence among them. Advances in functional and comparative genomics are needed in order to properly annotate these variants.The goal of this study is to: first, functionally annotate Common Variable Immunodeficiency disease (CVID) variants with the available bioinformatic methods in order to assess the reliability of these strategies. Sencondly, as the development of new methods to reduce the number of candidate genetic variants is an active and necessary field of research, we are exploring the utility of gene function information at organism level as a filter for rare disease genes identification. Recently, it has been proposed that only 10-15% of human genes are essential and therefore we would expect that severe rare diseases are mostly caused by mutations on them. Our goal is to determine whether or not these rare and severe diseases are caused by deleterious mutations in these essential genes. If this hypothesis were true, taking into account essential genes as a filter would be an interesting parameter to identify causingdisease mutations.

On an upper bound for the arithmetic self-intersection number of the dualizing sheaf on arithmetic surfaces

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On the number of limit cycles bifurcating from a non-global degenerated center

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Endogenous population subgroups: the best population partition and optimal number of groups

The aim of this paper is to suggest a method to find endogenously the points that group the individuals of a given distribution in k clusters, where k is endogenously determined. These points are the cut-points. Thus, we need to determine a partition of the N individuals into a number k of groups, in such way that individuals in the same group are as alike as possible, but as distinct as possible from individuals in other groups. This method can be applied to endogenously identify k groups in income distributions: possible applications can be poverty

Lower bounds for the number of limit cycles of trigonometric Abel equations

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On the upper bound of the number of limit cycles obtained by the second order averaging method I

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On the upper bound of the number of limit cycles obtained by the second order averaging method II

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Constrained school choice

Recently, several school districts in the US have adopted or consider adopting the Student-Optimal Stable Mechanism or the Top Trading Cycles Mechanism to assign children to public schools. There is clear evidence that for school districts that employ (variants of) the so-called Boston Mechanism the transition would lead to efficiency gains. The first two mechanisms are strategy-proof, but in practice student assignment procedures impede students to submit a preference list that contains all their acceptable schools. Therefore, any desirable property of the mechanisms is likely toget distorted. We study the non trivial preference revelation game where students can only declare up to a fixed number (quota) of schools to be acceptable. We focus on the stability of the Nash equilibrium outcomes. Our main results identify rather stringent necessary and sufficient conditions on the priorities to guaranteestability. This stands in sharp contrast with the Boston Mechanism which yields stable Nash equilibrium outcomes, independently of the quota. Hence, the transition to any of the two mechanisms is likely to come with a higher risk that students seek legal actionas lower priority students may occupy more preferred schools.

On the number of K3,3-minor-free and maximal K3,3-minor-free graphs

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Recepción y difusión internacionales de Mercè Rodoreda: obra original, crítica y traducción

RESUM Recepción y difusión internacionales de Mercè Rodoreda: obra original, crítica y traducción té per objecte determinar la recepció i la difusió de l’obra original de Mercè Rodoreda, així com de l’obra crítica i de les traduccions, en el context internacional a partir de la interpretació de quatre bases de dades: obra literària de Mercè Rodoreda, obra crítica de Mercè Rodoreda i la seva obra, traductors i traduccions en funció de la llengua i de l’obra i, per últim, presència documental de Mercè Rodoreda a les Biblioteques Nacionals del món. El treball de recerca s’estructura de la següent manera. En primer lloc, plantegem i delimitem el tema, els objectius, la metodologia i la descripció de les bases de dades. Acte seguit, interpretem les bases de dades i exposem algunes consideracions. A continuació, presentem les conclusions finals que hem desenvolupat en cadascun dels àmbits en els que se centra la nostra recerca, així com el projecte de tesi doctoral i les noves línies de recerca. Per últim, exposem la bibliografia i els annexes, en els que incloem les bases de dades i reproduim els estudis traductològics comentats en el treball. Amb l’elaboració d’aquest treball de recerca pretenem, entre d’altres, donar a conèixer els gèneres literaris que va cultivar Mercè Rodoreda; recopilar l’obra crítica al voltant de l’autora i distingir la seva temàtica per determinar el nombre d’estudis crítics sobre traducció; identificar quins títols de l’obra de Mercè Rodoreda s’han traslladat a altres llengües, així com confirmar quina és l’obra més traduïda i quines les llengües a les que s’ha traslladat la seva obra; i, per últim, constatar la presència d’obres originals, estudis crítics i traduccions a les Biblioteques Nacionals del món i identificar-ne les possibles àrees d’expansió.

Experimental investigation of transient natural convection cooling of high prandtl number fluid with variable viscosity

Report for the scientific sojourn at the James Cook University, Australia, between June to December 2007. Free convection in enclosed spaces is found widely in natural and industrial systems. It is a topic of primary interest because in many systems it provides the largest resistance to the heat transfer in comparison with other heat transfer modes. In such systems the convection is driven by a density gradient within the fluid, which, usually, is produced by a temperature difference between the fluid and surrounding walls. In the oil industry, the oil, which has High Prandtl, usually is stored and transported in large tanks at temperatures high enough to keep its viscosity and, thus the pumping requirements, to a reasonable level. A temperature difference between the fluid and the walls of the container may give rise to the unsteady buoyancy force and hence the unsteady natural convection. In the initial period of cooling the natural convection regime dominates over the conduction contribution. As the oil cools down it typically becomes more viscous and this increase of viscosity inhibits the convection. At this point the oil viscosity becomes very large and unloading of the tank becomes very difficult. For this reason it is of primary interest to be able to predict the cooling rate of the oil. The general objective of this work is to develop and validate a simulation tool able to predict the cooling rates of high Prandtl fluid considering the variable viscosity effects.

Computation of an integral basis of a quartic number field

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