Entropic transport: kinetics, scaling, and control mechanisms

We show that transport in the presence of entropic barriers exhibits peculiar characteristics which makes it distinctly different from that occurring through energy barriers. The constrained dynamics yields a scaling regime for the particle current and the diffusion coefficient in terms of the ratio between the work done to the particles and available thermal energy. This interesting property, genuine to the entropic nature of the barriers, can be utilized to effectively control transport through quasi-one-dimensional structures in which irregularities or tortuosity of the boundaries cause entropic effects. The accuracy of the kinetic description has been corroborated by simulations. Applications to different dynamic situations involving entropic barriers are outlined.

Características clínicas y tratamiento de la ansiedad académica y ante los exámenes como fobia específica de tipo situacional

L'ansietat acadèmica i davant els exàmens com a fòbia específica de tipus situacional és un trastorn infantil i juvenil d'efectes pertorbadors i negatius que repercuteixen sobre la salut mental i emocional, el rendiment acadèmic i la integració social de l'estudiant que la pateix. En aquest treball s'especifiquen les seves característiques clíniques. Així mateix, s'inclou un cas clínic d'un adolescent de 14 anys que patia d'aquest trastorn fòbic escolar, acompanyat de baixa autoestima personal i dificultats d'adaptació amb el seu grup-classe. Se li va aplicar una avaluació i tractament de tall cognitiu-conductual que ha tingut com a finalitat la superació de la fòbia, i la millora del seu rendiment acadèmic i social. D'entre totes les eines terapèutiques utilitzades destaquen: l'exposició en viu, i l'aprenentatge i utilització de mecanismes de control de l'ansietat (la relaxació Jacobson i la reestructuració cognitiva). Finalment, assenyalar que aquesta intervenció terapèutica ha estat possible gràcies a la participació coordinada i cooperant de l'equip interdisciplinari.

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.

Benchmarking for routines and organizational knowledge

We use best practice benchmarking rationales to propose a dynamic research design that accounts for the endogenous components of across-firms heterogeneous routines to study changes in performance and their link to organizational knowledge investments. We thus contribute to the operationalization of management theoretical frameworks based on resources and routines. The research design employs frontier measures that provide industry-level benchmarking in organizational settings, and proposes some new indicators for firm-level strategic benchmarking. A profit-oriented analysis of the U.S. technology industry during 2000-2011 illustrates the usefulness of our design. Findings reveal that industry revival following economic distress comes along with wider gaps between best and worst performers. Second stage analyses show that increasing intangibles stocks is positively associated with fixed target benchmarking, while enhancing R&D spending is linked to local frontier progress. The discussion develops managerial interpretations of the benchmarking measures that are suitable for control mechanisms and reward systems.

E2F1 regulates cellular growth by mTOR signaling

During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism

c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation.

Reinforcement versus Fluidization in Cytoskeletal Mechanoresponsiveness

Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

Universal Service Policies in Europe & Latam: Evidence on Bridging the Divide in Rural Areas

Broadband access is a key factor for economic and social development. However, providing broadband to rural areas is not attractive to private telecommunications operators due its low or zero investment return. To deal with broadband provision in rural areas, different governance systems based on private and public cooperation have appeared. This paper not only identifies and defines public and private cooperation models but also assesses their impact on overcoming the digital divide in rural areas. The results show that public ownership infrastructure under private management policy has had positive effects on reducing the broadband digital divide and being applied to areas with higher digital divide; subsides to private operators providers only positive effects on reducing broadband digital divide; but public infrastructure with public management programs did not. The results, obtained using quasi-experimental methods, suggest the importance of incentives and control mechanisms in broadband universal service provision plans.

The p38/MK2/Hsp25 pathway is required for BMP-2-induced cell migration.

Background: Bone morphogenetic proteins (BMPs) have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. Methodology/Principal Findings: Activation of p38 MAPK has been shown to be relevant for a number of BMP-2¿s physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38¿ or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. Conclusions: These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration.

Progressive Purkinje Cell Degeneration in tambaleante Mutant Mice Is a Consequence of a Missense Mutation in HERC1 E3 Ubiquitin Ligase

The HERC gene family encodes proteins with two characteristic domains: HECT and RCC1-like. Proteins with HECT domain shave been described to function as ubiquitin ligases, and those that contain RCC1-like domains have been reported to function as GTPases regulators. These two activities are essential in a number of important cellular processes such as cell cycle, cell signaling, and membrane trafficking. Mutations affecting these domains have been found associated with retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six HERC genes have been reported which encode two subgroups of HERC proteins: large (HERC1-2) and small (HERC3-6). The giant HERC1 protein was the first to be identified. It has been involved in membrane trafficking and cell proliferation/growth through its interactions with clathrin, M2-pyruvate kinase, and TSC2 proteins. Mutations affecting other members of the HERC family have been found to be associated with sterility and growth retardation. Here, we report the characterization of a recessive mutation named tambaleante, which causes progressive Purkinje cell degeneration leading to severe ataxia with reduced growth and lifespan in homozygous mice aged over two months. We mapped this mutation in mouse chromosome 9 and then performed positional cloning. We found a GuA transition at position 1448, causing a Gly to Glu substitution (Gly483Glu) in the highly conserved N- terminal RCC1-like domain of the HERC1 protein. Successful transgenic rescue, with either a mouse BAC containing the normal copy of Herc1 or with the human HERC1 cDNA, validated our findings. Histological and biochemical studies revealed extensive autophagy associated with an increase of the mutant protein level and a decrease of mTOR activity. Our observations concerning this first mutation in the Herc1 gene contribute to the functional annotation of the encoded E3 ubiquitin ligase and underline the crucial and unexpected role of this protein in Purkinje cell physiology.

Estudi neurofisiològic del control executiu de l'atenció en l'esquizofrènia

Report for the scientific sojourn carried out at the Departament de Psicologia de la Universitat de les Illes Balears, Spain, from May until July 2006. Abnormalities in executive functions, including set shifting ability, represent a cardinal feature in schizophrenia. This ability to adapt behavior to changing environmental events or contingencies requires a mechanism for switching attention between learned stimulus-response associations, or task-sets. This project aimed at gaining further knowledge on the brain mechanisms related to the executive control of attention in schizophrenia during the performace of a task switching paradigm. Furthermore, a secondary goal was to further examine the interrelationships between endogenous and exogenous control processes in task set switching.

Admission Control for TCP Flows Using Packet Classes and Edge-to-edge Measurements of Aggregates

TCP flows from applications such as the web or ftp are well supported by a Guaranteed Minimum Throughput Service (GMTS), which provides a minimum network throughput to the flow and, if possible, an extra throughput. We propose a scheme for a GMTS using Admission Control (AC) that is able to provide different minimum throughput to different users and that is suitable for "standard" TCP flows. Moreover, we consider a multidomain scenario where the scheme is used in one of the domains, and we propose some mechanisms for the interconnection with neighbor domains. The whole scheme uses a small set of packet classes in a core-stateless network where each class has a different discarding priority in queues assigned to it. The AC method involves only edge nodes and uses a special probing packet flow (marked as the highest discarding priority class) that is sent continuously from ingress to egress through a path. The available throughput in the path is obtained at the egress using measurements of flow aggregates, and then it is sent back to the ingress. At the ingress each flow is detected using an implicit way and then it is admission controlled. If it is accepted, it receives the GMTS and its packets are marked as the lowest discarding priority classes; otherwise, it receives a best-effort service. The scheme is evaluated through simulation in a simple "bottleneck" topology using different traffic loads consisting of "standard" TCP flows that carry files of varying sizes

Autonomía comunitaria y caciquismo: identidad étnica, control social y violencia en una comunidad mixe de Oaxaca

La etnografía de la comunidad mixe de Salto de la Tuxpana y del grave conflicto que se produjo entre 2005 y 2007 es el punto de partida del presente artículo. La investigación realizada arrojó como resultado más destacado el descubrimiento de un violento cacicazgo, legitimado ideológicamente en la autonomía comunitaria, la identidad étnica y el reclamo de una jurisdicción propia, y asentado firmemente sobre tres mecanismos de control social: protección a través de la Policía Comunitaria Armada, acceso a la tierra y acceso a los programas de «desarrollo». El caciquismo se define como el régimen político personalista, basado en estructuras clientelares, que monopoliza y controla recursos y votos. También se propone la hipótesis de que la mayor parte de la violencia desplegada por los caciques es el resultado del proceso de reproducción social del mismo sistema político, cuando se genera una faccionalización simétrica de la comunidad, después de un periodo de estabilidad complementaria.

Mechanisms of antagonism of Pseudomonas fluorescens EPS62e against Erwinia amylovora, the causal agent of fire blight

Pseudomonas fluorescens EPS62e was selected during a screening procedure for its high efficacy in controlling infections by Erwinia amylovora, the causal agent of fire blight disease, on different plant materials. In field trials carried out in pear trees during bloom, EPS62e colonized flowers until the carrying capacity, providing a moderate efficacy of fire-blight control. The putative mechanisms of EPS62e antagonism against E. amylovora were studied. EPS62e did not produce antimicrobial compounds described in P. fluorescens species and only developed antagonism in King’s B medium, where it produced siderophores. Interaction experiments in culture plate wells including a membrane filter, which physically separated the cultures, confirmed that inhibition of E. amylovora requires cell-to-cell contact. The spectrum of nutrient assimilation indicated that EPS62e used significantly more or different carbon sources than the pathogen. The maximum growth rate and affinity for nutrients in immature fruit extract were higher in EPS62e than in E. amylovora, but the cell yield was similar. The fitness of EPS62e and E. amylovora was studied upon inoculation in immature pear fruit wounds and hypanthia of intact flowers under controlled-environment conditions. When inoculated separately, EPS62e grew faster in flowers, whereas E. amylovora grew faster in fruit wounds because of its rapid spread to adjacent tissues. However, in preventive inoculations of EPS62e, subsequent growth of EPS101 was significantly inhibited. It is concluded that cell-to-cell interference as well as differences in growth potential and the spectrum and efficiency of nutrient use are mechanisms of antagonism of EPS62e against E. amylovora