Producció de material docent per a ciència de materials mitjançant microscòpia electrònica de rastreig i là ser confocal

Aquest projecte s'ha realitzat al Servei de Microscòpia de la Universitat Autònoma de Barcelona, i ha tingut una durada de dos anys (2006-2008). La finalitat d’aquest projecte ha estat l’elaboració de material didàctic basat en la captació d’imatges i l’edició de recursos pedagògics de suport digital aplicats a la ciència de materials. Es pretén millorar així la qualitat docent de les pràctiques de diverses assignatures dels ensenyaments de Física i d’Enginyeria de Materials utilitzant tècniques d’anàlisi actuals com són la Microscòpia Electrònica de Rastreig (MER) i la Microscòpia Optica (MO). Amb aquest projecte es vol fomentar també el treball interdisciplinari en equip entre professionals (docents i tècnics superiors de recerca) i acostar la teoria de les assignatures a la realització pràctica, facilitant el suport digital necessari per aconseguir un màxim aprofitament a les aules. Les imatges de MER i MO ajudaran als alumnes a familiaritzar-se amb el món de la recerca i la indústria.

Agents mòbils i DTN: disseny i implementació d'un protocol d'encaminament en l'entorn PROSES

En aquest projecte s’ha treballat en l’entorn PROSES, on aeroports i avions de l’espai aeri són mules de transport sobre una xarxa DTN. L’objectiu principal és estudiar i simular dos escenaris concrets: l’enviament de notícies des de les torres de control als avions, i l’enviament de canvis de rutes de vol dels avions a un aeroport en qüestió. S’ha simulat el comportament de dos protocols d’encaminament diferents sobre els escenaris creats. Per a realitzar les proves s’ha utilitzat el simulador The ONE, s’ha implementat un nou protocol d’encaminament, s’ha creat un Generador de Mapes i Rutes, i s’han realitzat amb èxit les simulacions.

Structural prediction of peptides bound to MHC class I.

An ab initio structure prediction approach adapted to the peptide-major histocompatibility complex (MHC) class I system is presented. Based on structure comparisons of a large set of peptide-MHC class I complexes, a molecular dynamics protocol is proposed using simulated annealing (SA) cycles to sample the conformational space of the peptide in its fixed MHC environment. A set of 14 peptide-human leukocyte antigen (HLA) A0201 and 27 peptide-non-HLA A0201 complexes for which X-ray structures are available is used to test the accuracy of the prediction method. For each complex, 1000 peptide conformers are obtained from the SA sampling. A graph theory clustering algorithm based on heavy atom root-mean-square deviation (RMSD) values is applied to the sampled conformers. The clusters are ranked using cluster size, mean effective or conformational free energies, with solvation free energies computed using Generalized Born MV 2 (GB-MV2) and Poisson-Boltzmann (PB) continuum models. The final conformation is chosen as the center of the best-ranked cluster. With conformational free energies, the overall prediction success is 83% using a 1.00 Angstroms crystal RMSD criterion for main-chain atoms, and 76% using a 1.50 Angstroms RMSD criterion for heavy atoms. The prediction success is even higher for the set of 14 peptide-HLA A0201 complexes: 100% of the peptides have main-chain RMSD values < or =1.00 Angstroms and 93% of the peptides have heavy atom RMSD values < or =1.50 Angstroms. This structure prediction method can be applied to complexes of natural or modified antigenic peptides in their MHC environment with the aim to perform rational structure-based optimizations of tumor vaccines.

Anà lisi i disseny d'un reflector per banda W

Les ones passives mil·limètriques (30 a 300GHz) tenen la peculiaritat de propagar-se en medis com la boira o la roba, a diferència del rang visible o l’infraroig. D’aquesta peculiaritat, surt l’interès de reproduir imatges per diverses aplicacions (seguretat, vigilància, etc...). És per aquest motiu que es treballa en el disseny d’un reflector per aquest tipus d’aplicació, treballant a una de les finestres de propagació d’aquest rang, la de la banda W. Es dissenyen i analitzen tres tipus de reflector: parabòlic simètric, offset i Cassegrain. D’aquests, s’estudien les seves figures de mèrit i directivitats buscant que aquestes siguin el més elevades possibles per obtenir una bona resolució, així com l’escaneig de l’escena de la qual es vol obtenir una imatge, veient aquí els efectes de les aberracions més comunes.

Redirecting anti-viral CTL against cancer cells by surface targeting of monomeric MHC class I-viral peptide conjugated to antibody fragments.

To combine the advantage of both the tumor targeting capacity of high affinity monoclonal antibodies (mAbs) and the potent killing properties of cytotoxic T lymphocytes (CTL), we investigated the activity of conjugates made by coupling single Fab' fragments, from mAbs specific for tumor cell surface antigens, to monomeric HLA-A2 complexes containing the immunodominant influenza-matrix peptide 58-66. In solution, the monovalent 95 kDa Fab-HLA-A2/Flu conjugates did not activate influenza-specific CTL. However, when targeted to tumor cells expressing the relevant tumor-associated antigen, the conjugates induced CTL activation and efficient tumor cell lysis, as a result of MHC/peptide surface oligomerization. The highly specific and sensitive in vitro cytotoxicity results presented suggest that injection of Fab-MHC/peptide conjugates could represent a new form of immunotherapy, bridging antibody and T lymphocyte attack on cancer cells.

A single mutation in enzyme I of the sugar phosphotransferase system confers penicillin tolerance to Streptococcus gordonii.

Tolerance is a poorly understood phenomenon that allows bacteria exposed to a bactericidal antibiotic to stop their growth and withstand drug-induced killing. This survival ability has been implicated in antibiotic treatment failures. Here, we describe a single nucleotide mutation (tol1) in a tolerant Streptococcus gordonii strain (Tol1) that is sufficient to provide tolerance in vitro and in vivo. It induces a proline-to-arginine substitution (P483R) in the homodimerization interface of enzyme I of the sugar phosphotransferase system, resulting in diminished sugar uptake. In vitro, the susceptible wild-type (WT) and Tol1 cultures lost 4.5 and 0.6 log(10) CFU/ml, respectively, after 24 h of penicillin exposure. The introduction of tol1 into the WT (WT P483R) conferred tolerance (a loss of 0.7 log(10) CFU/ml/24 h), whereas restitution of the parent sequence in Tol1 (Tol1 R483P) restored antibiotic susceptibility. Moreover, penicillin treatment of rats in an experimental model of endocarditis showed a complete inversion in the outcome, with a failure of therapy in rats infected with WT P483R and the complete disappearance of bacteria in animals infected with Tol1 R483P.

Entrevistant infants pre-escolars víctimes d’abús sexual i/o maltractament familiar : Eficà cia dels models d’entrevista forense

Entrevistant infants pre-escolars víctimes d’abús sexual i/o maltractament familiar: eficàcia dels models d’entrevista forense Entrevistar infants en edat preescolar que han viscut una situació traumàtica és una tasca complexa que dins l’avaluació psicològica forense necessita d’un protocol perfectament delimitat, clar i temporalitzat. Per això, s’han seleccionat 3 protocols d’entrevista: el Protocol de Menors (PM) de Bull i Birch, el model del National Institute for Children Development (NICHD) de Michel Lamb, a partir del qual es va desenvolupar l’EASI (Evaluación del Abuso Sexual Infantojuvenil) i l’Entrevista Cognitiva (EC) de Fisher i Geiselman. La hipòtesi de partida vol comprovar si els anteriors models permeten obtenir volums informatius diferents en infants preescolars. Conseqüentment, els objectius han estat determinar quin dels models d’entrevista permet obtenir un volum informatiu amb més precisions i menys errors, dissenyar un model d’entrevista propi i consensuar aquest model. En el treball s’afegeixen esquemes pràctics que facilitin l’obertura, desenvolupament i tancament de l’entrevista forense. La metodologia ha reproduït el binomi infant - esdeveniment traumàtic, mitjançant la visualització i l’explicació d’un fet emocionalment significatiu amb facilitat per identificar-se: l’accident en bicicleta d’un infant que cau, es fa mal, sagna i el seu pare el cura. A partir d’aquí, hem entrevistat 135 infants de P3, P4 i P5, mitjançant els 3 models d’entrevista referits, enfrontant-los a una demanda específica: recordar i narrar aquest esdeveniment. S’ha conclòs que el nivell de record correcte, quan s’utilitza un model d’entrevista adequat amb els infants en edat preescolar, oscil•la entre el 70-90%, fet que permet defensar la confiança en els records dels infants. Es constata que el percentatge d’emissions incorrectes dels infants en edat preescolar és mínim, al voltant d’un 5-6%. L’estudi remarca la necessitat d’establir perfectament les regles de l’entrevista i, per últim, en destaca la ineficàcia de les tècniques de memòria de l’entrevista cognitiva en els infants de P3 i P4. En els de P5 es comencen a veure beneficis gràcies a la tècnica de la reinstauració contextual (RC), estant les altres tècniques fora de la comprensió i utilització dels infants d’aquestes edats. Interviewing preschoolers victims of sexual abuse and/or domestic abuse: Effectiveness of forensic interviews models 135 preschool children were interviewed with 3 different interview models in order to remember a significant emotional event. Authors conclude that the correct recall of children ranging from 70-90% and the percentage of error messages is 5-6%. It is necessary to fully establish the rules of the interview. The present research highlights the effectiveness of the cognitive interview techniques in children from P3 and P4. Entrevistando niños preescolares víctimas de abuso sexual y/o maltrato familiar: eficacia de los modelos de entrevista forense Se han entrevistado 135 niños preescolares con 3 modelos de entrevista diferentes para recordar un hecho emocionalmente significativo. Se concluye que el recuerdo correcto de los niños oscila entre el 70-90% y el porcentaje de errores de mensajes es del 5-6%. El estudio remarca la necesidad de establecer perfectamente las reglas de la entrevista y se destaca la ineficacia de las técnicas de la entrevista cognitiva en los niños de P3 y P4.

Recombinant human insulin-like growth factor I (rhIGF-I) for the treatment of amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Recombinant human insulin-like growth factor I (rhIGF-I) is a possible disease modifying therapy for amyotrophic lateral sclerosis (ALS, which is also known as motor neuron disease (MND)). OBJECTIVES: To examine the efficacy of rhIGF-I in affecting disease progression, impact on measures of functional health status, prolonging survival and delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival in ALS. Occurrence of adverse events was also reviewed. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (21 November 2011), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to November 2011) and EMBASE (January 1980 to November 2011) and sought information from the authors of randomised clinical trials and manufacturers of rhIGF-I. SELECTION CRITERIA: We considered all randomised controlled clinical trials involving rhIGF-I treatment of adults with definite or probable ALS according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months of treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: Each author independently graded the risk of bias in the included studies. The lead author extracted data and the other authors checked them. We generated some missing data by making ruler measurements of data in published graphs. We collected data about adverse events from the included trials. MAIN RESULTS: We identified three randomised controlled trials (RCTs) of rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European trial (183 participants) the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a North American trial (266 participants), the MD after nine months was -6.00 (95% CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. There was an increased risk of injection site reactions with rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial (330 participants) used a novel primary end point involving manual muscle strength testing. No differences were demonstrated between the treated and placebo groups in this study. All three trials were at high risk of bias. AUTHORS' CONCLUSIONS: Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias.

Pla de gestió de la finca Solà i Comes (Bellver de Cerdanya, 2011)

La finca Solà i Comes, situada a la solana del municipi de Bellver de Cerdanya, enfront la serra del Cadí-Moixeró, és un espai natural que combina el paisatge forestal amb un mosaic de prats i pastures, aprofitats per l’activitat ramadera extensiva que es practica a la zona. Les activitat agrícoles i ramaderes són, des de temps enrere, activitats fortament lligades al medi natural: el clima, la geologia i els ecosistemes han determinat els tipus de cultiu i també el tipus de ramaderia. I al seu torn, aquestes activitats han actuat sobre el medi, modelant el paisatge i configurant uns hàbitats amb unes condicions ecològiques molt específiques que mantenen una relació molt intensa amb els hàbitats naturals més propers (com les zones arbustives, marges, bosquets, cursos d’aigua...) i que constitueixen importants extensions del paisatge del nostre país. La diversitat biològica que produeixen aquests espais és essencial per mantenir un equilibri ambiental i obtenir uns recursos dels quals depèn la nostra qualitat de vida i el desenvolupament de bona part de la nostra activitat econòmica. En aquest pla de gestió es vol donar importància no només a la conservació dels hàbitats, sinó també a la principal activitat econòmica que fa possible que aquests hàbitats romanguin igual que fa uns anys: la ramaderia extensiva actualment en fort retrocés a Catalunya i a la resta d’Europa. En el document del pla de gestió es fa una descripció detallada del conjunt de la finca que inclou tots els àmbits, partint del punt de vista administratiu fins al físic, ecològic, biològic i socioeconòmic. Una vegada situats en el context de la zona d’estudi, s’avaluen els objectius que es volen dur a terme i es proposen mesures de gestió per poder-los assolir. A continuació, es fa un breu resum dels aspectes descriptius de la zona d’estudi, destacant els punts més rellevants, i es comenten les mesures de gestió proposades a línies generals per a cadascun. Les mesures de gestió proposades són fruit d’una avaluació dels factors limitants que trobem sobre els objectius ideals plantejats per a l’espai. D’aquesta avaluació se’n deriven els objectius operacionals a partir dels quals es creen les propostes de gestió.

A phase I study of the oral platinum agent satraplatin in sequential combination with capecitabine in the treatment of patients with advanced solid malignancies.

Abstract Background. The broad spectrum of antitumor activity of both the oral platinum analogue satraplatin (S) and capecitabine (C), along with the advantage of their oral administration, prompted a clinical study aimed to define the maximum tolerated dose (MTD) of the combination. Patients and methods. Four dose levels of S (mg/m(2)/day) and C (mg/m(2)/day) were evaluated in adult patients with advanced solid tumors: 60/1650, 80/1650, 60/2000, 70/2000; a course consisted of 28 days with sequential administration of S (days 1-5) and C (days 8-21) followed by one week rest. Results. Thirty-seven patients were treated, 24 in the dose escalation and 13 in the expansion phase; at the MTD, defined at S 70/C 2000, two patients presented dose limiting toxicities: lack of recovery of neutropenia by day 42 and nausea with dose skip of C. Most frequent toxicities were nausea (57%), diarrhea (51%), neutropenia (46%), anorexia, fatigue, vomiting (38% each). Two partial responses were observed in platinum sensitive ovarian cancer and one in prostate cancer. Conclusion. At S 70/C 2000 the combination of sequential S and C is tolerated with manageable toxicities; its evaluation in platinum and fluorouracil sensitive tumor types is worthwhile because of the easier administration and lack of nephro- and neurotoxicity as compared to parent compounds.

LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.

Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8+ T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2)). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11)-10(-9)) and African (p = 10(-5)-10(-3)) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.

Genomics of the divergence continuum in an African plant biodiversity hotspot, I: drivers of population divergence in Restio capensis (Restionaceae).

Understanding the drivers of population divergence, speciation and species persistence is of great interest to molecular ecology, especially for species-rich radiations inhabiting the world's biodiversity hotspots. The toolbox of population genomics holds great promise for addressing these key issues, especially if genomic data are analysed within a spatially and ecologically explicit context. We have studied the earliest stages of the divergence continuum in the Restionaceae, a species-rich and ecologically important plant family of the Cape Floristic Region (CFR) of South Africa, using the widespread CFR endemic Restio capensis (L.) H.P. Linder & C.R. Hardy as an example. We studied diverging populations of this morphotaxon for plastid DNA sequences and >14 400 nuclear DNA polymorphisms from Restriction site Associated DNA (RAD) sequencing and analysed the results jointly with spatial, climatic and phytogeographic data, using a Bayesian generalized linear mixed modelling (GLMM) approach. The results indicate that population divergence across the extreme environmental mosaic of the CFR is mostly driven by isolation by environment (IBE) rather than isolation by distance (IBD) for both neutral and non-neutral markers, consistent with genome hitchhiking or coupling effects during early stages of divergence. Mixed modelling of plastid DNA and single divergent outlier loci from a Bayesian genome scan confirmed the predominant role of climate and pointed to additional drivers of divergence, such as drift and ecological agents of selection captured by phytogeographic zones. Our study demonstrates the usefulness of population genomics for disentangling the effects of IBD and IBE along the divergence continuum often found in species radiations across heterogeneous ecological landscapes.

Phase I and phase II xenobiotic reactions and metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in aggregating liver cell cultures.

Aggregating fetal liver cell cultures were tested for their ability to metabolize xenobiotics using ethoxycoumarin-O-deethylase (ECOD), as marker of phase I metabolism, and glutathione S-transferase (GST), as marker for phase II reactions. Significant basal activities, stable over 14 days in culture were measured for both ECOD and GST activities. The prototype cytochrome P450 inducers, 3-methylcholanthrene (3-MC) and phenobarbital (PB), increased ECOD and GST activities reaching an optimum 7 days after culturing, followed by a decline in activity. This decline was partially prevented by 1% dimethyl sulfoxide (DMSO) added chronically to the culture medium. DMSO was also found to induce ECOD activity and to a lesser extent GST activity. Furthermore, it potentiated in a dose-dependent manner the induction of ECOD by PB. The food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is metabolically transformed through a number of pathways in vivo. It was therefore used to examine the metabolic capacity in fetal and adult liver cell aggregates. Metabolism of MeIQx was mainly through N2-conjugation, resulting in formation of the N2-glucuronide and sulfamate conjugates for non-induced fetal liver cells. These metabolites were also found in large amounts in non-induced adult liver cells. Low levels of cytochrome P450-mediated ring-hydroxylated metabolites were detected in both non-induced fetal and adult liver cells. After induction with arochlor (PCB) or 3-MC, the major pathway was ring-hydroxylation (cytochrome P450 dependent), followed by conjugation to beta-glucuronic or sulfuric acid. The presence of the glucuronide conjugate of N-hydroxy-MeIQx, a mutagenic metabolite, suggested an induction of P450 CYP1A2. The metabolism of MeIQx by liver cell aggregates is very similar to that observed in vivo and suggests that aggregating liver cell cultures are a useful model for in vitro metabolic studies in toxicology.

El procés de desistiment de les persones empresonades. Obstacles i suports

La recerca aborda els mecanismes de transició entre la presó i la vida en llibertat i, particularment, el paper que aquests juguen en els processos de desistiment del delicte. Centrant-se en població masculina condemnada a presó per delictes patrimonials i/o contra la salut pública, la recerca vol identificar les narratives de desistiment i persistència en l’activitat delictiva, i conèixer com determinats factors externs contribueixen a la construcció d’aquestes narratives. Aquests factors externs són concebuts com a punts d’inflexió que poden propiciar el canvi, i estan relacionats tant amb allò tractat i viscut dins la presó com amb els suports i vincles existents en la comunitat on es desemboca. Així mateix, aquests processos de transició es contextualitzen tant en el marc d’una trajectòria passada (familiar, formativa-laboral, delictiva i penitenciària) com també en la fase del cicle vital en què hom se situa, en tant que aquests dos eixos delimiten, en bona mesura, l’estructura d’oportunitats i els marcs de referència de la persona al sortir de la presó. Amb aquest objectiu s’ha plantejat un disseny prospectiu en dues onades: la primera onada contempla la realització d’entrevistes personals narratives durant les setmanes prèvies a la finalització de la condemna de presó per conèixer la biografia, la darrera etapa a la presó i les narratives sobre la transició; la segona onada està previst fer-la un any després de la finalització de la condemna i estarà centrada en l’anàlisi del procés de transició. Aquest informe presenta els resultats de la primera onada.