A Monte Carlo-Based Fiber Tracking Algorithm using Diffusion Tensor MRI

Diffusion tensor magnetic resonance imaging, which measures directional information of water diffusion in the brain, has emerged as a powerful tool for human brain studies. In this paper, we introduce a new Monte Carlo-based fiber tracking approach to estimate brain connectivity. One of the main characteristics of this approach is that all parameters of the algorithm are automatically determined at each point using the entropy of the eigenvalues of the diffusion tensor. Experimental results show the good performance of the proposed approach

Multifunctional ligands for application in Alzheimer’s Disease: molecular modelling and biological evaluation

Projecte de recerca elaborat a partir d’una estada a la University of British Columbia, Canadà, entre 2010 i 2012 La malaltia d'Alzheimer (MA) representa avui la forma més comuna de demència en la població envellida. Malgrat fa 100 anys que va ser descoberta, encara avui no existeix cap tractament preventiu i/o curatiu ni cap agent de diagnòstic que permeti valorar quantitativament l'evolució d'aquesta malaltia. L'objectiu en el que s'emmarca aquest treball és contribuir a aportar solucions al problema de la manca d'agents terapèutics i de diagnosi, unívocs i rigorosos, per a la MA. Des del camp de la química bioinorgànica és fàcil fixar-se en l'excessiva concentració d'ions Zn(II) i Cu(II) en els cervells de malalts de MA, plantejar-se la seva utilització com a dianes terapèutica i, en conseqüència, cercar agents quelants que evitin la formació de plaques senils o contribueixin a la seva dissolució. Si bé aquest va ser el punt de partida d’aquest projecte, els múltiples factors implicats en la patogènesi de la MA fan que el clàssic paradigma d’ ¨una molècula, una diana¨ limiti la capacitat de la molècula de combatre aquesta malaltia tan complexa. Per tant, un esforç considerable s’ha dedicat al disseny d’agentsmultifuncionals que combatin els múltiples factors que caracteritzen el desenvolupament de la MA. En el present treball s’han dissenyat agents multifuncionals inspirats en dos esquelets moleculars ben establers i coneguts en el camp de la química medicinal: la tioflavina-T (ThT) i la deferiprona (DFP). La utilització de tècniques in silico que inclouen càlculs farmacocinètics i modelatge molecular ha estat un procés cabdal per a l’avaluació dels millors candidats en base als següents requeriments: (a) compliment de determinades propietats farmacocinètiques que estableixin el seu possible ús com a fàrmac (b) hidrofobicitat adequada per travessar la BBB i (c) interacció amb el pèptid Aen solució.

Famílies immigrades i escoles: dinàmiques de relació a Catalunya

A Catalunya els discursos acadèmics i de l'administració han anat evolucionant fins que s'han imposat aquells que apunten a que la relació entre l'escola, la família i l'entorn és clau per l'èxit escolar de l'alumnat i el bon funcionament del sistema educatiu. Malgrat aquesta evolució, en la pràctica el canvi és lent i, sovint, complicat, donat que apareixen resistències en les dues institucions, família i escola, degut a que fins avui sempre s'ha mantingut una relació marcada pel desequilibri de poder. El nostre treball teòric i, sobretot, empíric s'ha centrat en la relació entre la família immigrada i l'escola a Catalunya. Com es presentarà, la creació del que hem anomenat dinàmiques positives de relació i comunicació en els centres escolars es troba condicionada per les actituds i els comportaments dels equips directius, els professionals i les famílies, tot i que també l'espai físic en que es donen aquestes relacions és important. Respecte a la organització del centre hem destacat el papel de l'equip directiu. Diferenciant una models de gestió observem aquells més facilitadors de la relació i la comunicació amb i entre les famílies i aquells més desincentivadors. Això sí, sempre s'ha de tenir en compte les actituds dels docents i de les famílies que són múltiples i complexes.

Human Capital, the Structure of Production, and Growth

Recent decisions by the Spanish national competition authority (TDC) mandate payment systems to include only two costs when setting their domestic multilateral interchange fees (MIF): a fixed processing cost and a variable cost for the risk of fraud. This artificial lowering of MIFs will not lower consumer prices, because of uncompetitive retailing; but it will however lead to higher cardholders fees and, likely, new prices for point of sale terminals, delaying the development of the immature Spanish card market. Also, to the extent that increased cardholders fees do not offset the fall in MIFs revenue, the task of issuing new cards will be underpaid relatively to the task of acquiring new merchants, causing an imbalance between the two sides of the networks. Moreover, the pricing scheme arising from the decisions will cause unbundling and underprovision of those services whose costs are excluded. Indeed, the payment guarantee and the free funding period will tend to be removed from the package of services currently provided, to be either provided by third parties, by issuers for a separate fee, or not provided at all, especially to smaller and medium-sized merchants. Transaction services will also suffer the consequences that the TDC precludes pricing them in variable terms.

Do market conditions affect preferences? Evidence from experimental markets with excess supply and excess demand

We study whether people's preferences in an unbalanced market are affected by whether they are on the excess supply side or the excess demand side of the market. Our analysis is based on the comparison of behavior between two types of experimental gift exchange markets, which vary only with respect to whether first or second movers are on the long side of the market. The direction of market imbalance could influence subjects' motivation, as second movers, workers, might react differently to favorable actions by first movers, firms, in the two cases. Our data show strong deviations from the standard game-theoretic prediction. However, we only find secondary treatment effects. First movers are not more generous when they are in excess supply and second movers do not respond less favorably when they are in excess demand. Competition has only minor psychological effects in our data.

Fiscal decentralization in Spain: An asymmetric transition to democracy

Asymmetric fiscal decentralization, by which we mean different fiscal arrangements between the central government and different groups of, or individual, lower-level governments, may be justified from an economic efficiency perspective. As argued by Tiebout (1956), Oates (1972) and others, a decentralized system of regional and local governments is better able to accommodate differences in tastes for public goods and services. This efficiency argument calls for decentralization of fiscal authority to regional and local governments, but not necessarily asymmetric decentralization. However, when the differences in tastes for public goods and services arise out of differences in history, culture and language across regions of a country, asymmetric treatment may be justified. History, culture and language may influence how a group of people (a region) views autonomy, independence and fiscal authority. Some regions may have had experience with autonomous government in the past, they may have a culture that is strongly reliant upon (or leery of) the central government, or they may be fearful of losing their separate languages if they do not have special arrangements. To accommodate differences in taste for independence, autonomy, and fiscal authority, it may be necessary to have different fiscal arrangements between the central government and the different regions comprising the country.

Price regulation of plastic money: A critical assessment of Spanish rules

Recent decisions by the Spanish national competition authority (TDC) mandate paymentsystems to include only two costs when setting their domestic multilateral interchange fees(MIF): a fixed processing cost and a variable cost for the risk of fraud. This artificiallowering of MIFs will not lower consumer prices, because of uncompetitive retailing; but itwill however lead to higher cardholders fees and, likely, new prices for point of saleterminals, delaying the development of the immature Spanish card market. Also, to the extent that increased cardholders fees do not offset the fall in MIFs revenue, the task of issuing new cards will be underpaid relatively to the task of acquiring new merchants, causing an imbalance between the two sides of the networks. Moreover, the pricing scheme arising from the decisions will cause unbundling and underprovision of those services whose costs are excluded. Indeed, the payment guarantee and the free funding period will tend to be removed from the package of services currently provided, to be either provided by third parties, by issuers for a separate fee, or not provided at all, especially to smaller and medium-sized merchants. Transaction services will also suffer the consequences that the TDC precludes pricing them in variable terms.

Array-CGH in patients with a clinical diagnosis of Kabuki syndrome: identification of two cases with terminal 2q37 deletion and no other recurrent rearrangement

Background: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods: We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results: No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion: Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

Control d'una bobinadora automàtica

Un dels problemes típics de regulació en el camp de l’automatització industrial és el control de velocitat lineal d’entrada del fil a les bobines, ja que com més gruix acumulem a igual velocitat de rotació de la bobina s’augmenta notablement la velocitat lineal d’entrada del fil, aquest desajust s’ha de poder compensar de forma automàtica per aconseguir una velocitat d’entrada constant. Aquest problema de regulació de velocitats és molt freqüent i de difícil control a la indústria on intervé el bobinat d’algun tipus de material com cablejat, fil, paper, làmines de planxa, tubs, etc... Els dos reptes i objectius principals són, primer, la regulació de la velocitat de rotació de la bobina per aconseguir una velocitat lineal del fil d’entrada, i segon, mitjançant el guiatge de l’alimentació de fil a la bobina, aconseguir un repartiment uniforme de cada capa de fil. El desenvolupament consisteix amb l’automatització i control d’una bobinadora automàtica mitjançant la configuració i programació de PLC’s, servomotors i encoders. Finalment es farà el muntatge pràctic sobre una bancada per verificar i simular el seu correcte funcionament que ha de donar solució a aquests problemes de regulació de velocitats. Com a conclusions finals s’han aconseguit els objectius i una metodologia per fer una regulació de velocitats de rotació per bobines, amb accionaments de servomotors amb polsos, i a nivell de coneixements he aconseguit dominar les aplicacions d’aquest tipus d’accionaments aplicats a construccions mecàniques.

Análisis de la fiabilidad de indicadores para sistemas de seguimiento de precios en los mercados

Para este trabajo se ha desarrollado un programa en Matlab, que nos permite realizar ensayos con algunas de las herramientas fundamentales del análisis técnico. Concretamente nos hemos centrado en el “Indicador de Movimiento Direccional” de Wilder. El programa está formado por seis funciones que permiten descargar datos, hacer la simulación del indicador, ajustar automáticamente algunos de sus parámetros y presentar los resultados obtenidos en la simulación. Con los experimentos y simulaciones realizadas se ha visto la importancia de escoger adecuadamente los períodos de ±DIs (indicadores direccionales positivo y negativo) y el ADX (Average Directional Movement Index). También hemos visto que la reglas decisión apuntadas por autores de reconocido prestigio como Cava y Ortiz ,no siempre se comportan como cabría esperar. Se propone mejorar el rendimiento y la fiabilidad de este indicador Incluyendo alguna media móvil de los precios y el volumen de contratación, en los criterios de decisión. También se podría mejorar implementando un sistema para que se pudiesen autoajustar los criterios de decisión.

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A2 (cPLA2) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA2 inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4¿dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway.

Diffusionless first-order phase transitions in systems with frozen configurational degrees of freedom

We consider systems that can be described in terms of two kinds of degree of freedom. The corresponding ordering modes may, under certain conditions, be coupled to each other. We may thus assume that the primary ordering mode gives rise to a diffusionless first-order phase transition. The change of its thermodynamic properties as a function of the secondary-ordering-mode state is then analyzed. Two specific examples are discussed. First, we study a three-state Potts model in a binary system. Using mean-field techniques, we obtain the phase diagram and different properties of the system as a function of the distribution of atoms on the different lattice sites. In the second case, the properties of a displacive structural phase transition of martensitic type in a binary alloy are studied as a function of atomic order. Because of the directional character of the martensitic-transition mechanism, we find only a very weak dependence of the entropy on atomic order. Experimental results are found to be in quite good agreement with theoretical predictions.

Anomalous specific-heat jump in a two-component ultracold Fermi gas

The thermodynamic functions of a Fermi gas with spin population imbalance are studied in the temperature-asymmetry plane in the BCS limit. The low-temperature domain is characterized by an anomalous enhancement of the entropy and the specific heat above their values in the unpaired state, decrease of the gap and eventual unpairing phase transition as the temperature is lowered. The unpairing phase transition induces a second jump in the specific heat, which can be measured in calorimetric experiments. While the superfluid is unstable against a supercurrent carrying state, it may sustain a metastable state if cooled adiabatically down from the stable high-temperature domain. In the latter domain the temperature dependence of the gap and related functions is analogous to the predictions of the BCS theory.

Comparative effects of oleoyl-estrone and a specific b3-adrenergic agonist (CL316, 243) on the expression of genes involved in energy metabolism of rat white adipose tissue

Background: The combination of oleoyl-estrone (OE) and a selective b3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid). Methods: In the present study we investigated the effect of OE (oral gavage) and/or B3A (subcutaneous constant infusion) administration for 10 days to overweight male rats, compared with controls, on three distinct white adipose tissue (WAT) sites: subcutaneous inguinal, retroperitoneal and epididymal. Tissue weight, DNA (and, from these values cellularity), cAMP content and the expression of several key energy handling metabolism and control genes were analyzed and computed in relation to the whole site mass. Results: Both OE and B3A significantly decreased WAT mass, with no loss of DNA (cell numbers). OE decreased and B3A increased cAMP. Gene expression patterns were markedly different for OE and B3A. OE tended to decrease expression of most genes studied, with no changes (versus controls) of lipolytic but decrease of lipogenic enzyme genes. The effects of B3A were widely different, with a generalized increase in the expression of most genes, including the adrenergic receptors, and, especially the uncoupling protein UCP1. Discussion: OE and B3A, elicit widely different responses in WAT gene expression, end producing similar effects, such as shrinking of WAT, loss of fat, maintenance of cell numbers. OE acted essentially on the balance of lipolysislipogenesis and the blocking of the uptake of substrates; its decrease of synthesis favouring lipolysis. B3A induced a shotgun increase in the expression of most regulatory systems in the adipocyte, an effect that in the end favoured again the loss of lipid; this barely selective increase probably produces inefficiency, which coupled with the increase in UCP1 expression may help WAT to waste energy through thermogenesis. Conclusions: There were considerable differences in the responses of the three WAT sites. OE in general lowered gene expression and stealthily induced a substrate imbalance. B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation. There was not a synergistic effect between OE and B3A in WAT, but their combined action increased WAT energy waste.

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A2 (cPLA2) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA2 inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4¿dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway.