Plancto e hidrobiologia sanitária de tanques tropicais com dáfnias e rotíferos

The engineers of the modern University City are constructing a graceful bridge, named PONTE OSWALDO CRUZ, that crosses a portion of the Guanabara Bay (Fig. 1). The work at west pillar stopped for 3 years (The concret structure in Est. 1). As it will be seen from n.º 1 — 5 of the fig. 1, Est. I, the base of the structure will have five underground boxes of reinforcement, but, to-day they are just like as five uncovered water ponds, until at present: May 1963. (Est. I — fig. 3, n.º 3 — pond n.º 3; A. — old level of the water; B.— actual level of the water; c.— green water; E.— mass of bloom of blue algae Microcystis aeruginosa). Soon after SW portion, as 5 cells in series, of the pillar abutments, and also the NE portion nearly opposite in the Tibau Mount will be filled up with earth, a new way will link Rio City and the University City. We see to day Est. I, fig. 1 — the grasses on the half arenous beach of the Tibau Point. These natural Cyperaceae and Gramineae will be desappear because of so a new road, now under construction, when completed will be 33 feet above the mean sea level, as high as the pillar, covering exactly as that place. Although rainfall was the chief source of water for these ponds, the first water (before meterorological precipitations of whatever first rain it might fall) was a common tap water mixed with Portland Cement, which exuded gradually through the pores of the concret during its hardenning process. Some data of its first cement water composition are on the chemical table, and in Tab. n.º 4 and "Resultado n.º 1". The rain — receiving surface of each pond were about 15 by 16 feet, that is, 240 square feet; when they were full of water, their depth was of 2 feet 3", having each pond about 4,000 gallons. Climatic conditions are obviously similar of those of the Rio de Janeiro City: records of temperature, of precipitation and evaporation are seen on the graphics, figs. 2, 3, 4. Our conceptions of 4 phases is merely to satisfy an easy explanation thus the first phase that of exudation of concrete. We consider the 2nd. phase formation of bacterian and cyanophycean thin pellicel. 3rd. phase - dilution by rains, and fertilisation by birds; the 4th phase - plankton flora and fauna established. The biological material arrived with the air, the rains, and also with contaminations by dusts; with big portion of sand, of earth, and leaves of trees resulted of the SW wind actions in the storming days (See - Est. I, fig. 3, G. - the mangrove trees of the Pinheiro Island). Many birds set down and rest upon the pillar structure, its faeces which are good fertilizers fall into the ponds. Some birds were commonly pigeons, black ravens, swallows, sparrows and other sea mews, moor hens, and a few sea birds of comparatively rare occurence. We get only some examples of tropical dust contaminated helioplankton, of which incipient observations were been done sparcely. See the systematic list of the species of plankters. Phytoplankters - Cyanophyta algae as a basic part for food of zooplankters, represented chiefly by rotiferse, water-fleas Moinodaphnia and other Crustacea: Ostracoda Copepoda and Insecta: Chironomidae and Culicidae larvae. The polysaprobic of septic irruptions have not been done only by heating in summer, and, a good reason of that, for example: when the fifth pond was in polysaprobic phase as the same time an alike septic phase do not happened into the 3rd. pond, therefore, both were in the same conditions of temperature, but with unlike contaminations. Among the most important aquatic organisms used as indicatiors of pollution - and microorganisms of real importance in the field of sanitary science, by authorities of renown, for instance: PALMER, PRESCOTT, INGRAM, LIEBMANN, we choose following microalgae: a) The cosmopolite algae Scenedesmus quadricuada, a common indicator in mesosaprobio waters, which lives between pH 7,0 and it is assimilative of NO[3 subscripted] and NH[4 subscripted]. b) Species of the genus Chlamydomonas; it is even possible that all the species of theses genus inhabit strong-mesosaprobic to polysaprobic waters when in massive blooms. c) Several species of Euglenaceae in fast growing number, at the same time of the protozoa Amoebidae, Vorticellidae and simultaneous with deposition of the decaying cells of the blue algae Anacystis cyanea (= Microcystis) when the consumed oxygen by organic matter resulted in 40 mg. L. But, we found, among various Euglenacea the cosmopolite species (Euglena viridis, a well known polysaprobic indicatior of which presence occur in septic zone. d) Analcystis cyanea (= M. aeruginosa) as we observed was in blooms increasing to the order of billions of cells per litter, its maximum in the summer. Temperatures 73ºF to 82ºF but even 90ºF, the pH higher than 8. When these blue algae was joined to the rotifer Brachionus calyflorus the waters gets a milky appearance, but greenished one. In fact, that cosmopolite algae is used as a mesosaprobic indicator. Into the water of the ponds its predominance finished when the septic polysaprobic conditions began. e) Ankistrodesmus falcatus was present in the 5th pond from 26the. April untill the 26th July, and when N.NH[4 subscripted] gets 1.28 mg. L. and when chlorinity stayed from 0.034 to 0.061 mg. L. It never was found at N.NH[4 subscripted] higher than 1 mg. L. The green algae A. falcatus, an indicatior of pollution, lives in moderate mesosaprobic waters. f) As everyone knows, the rotifer eggs may be widely dispersed by wind. The rotifer Asplanchna brightwelli in our observation seemed like a green colored bag, overcharged by green cells and detritus, specially into its spacious stomach, which ends blindly (the intestine, cloaca, being absent). The stock of Asplanchna in the ponds, during the construction of the bridge "PONTE OSWALDO CRUZ" inhabits alkaline waters, pH 8,0 a 8,3, and when we observed we noted its dissolved oxygen from 3.5 to 4 mg. L. In these ponds Asplanchna lived in 0,2 P.PO[4 subscripted]. (Remember the hydobiological observations foreign to braslian waters refer only from 0.06 to 0,010 mg. L. P.PO[4 subscripted]; and they refer resistance to 0.8 N.NH[4 subscripted]). By our data, that rotiger resist commonly to 1.2 until 1.8 mg. L.N.NH[4 subscripted]; here in our ponds and, when NO[2 subscripted] appears Asplanchna desappears. It may be that Asplanchna were devoured by nitrite resistant animals of by Culicidae or other mosquitoes devoured by Due to these facts the number and the distribution of Asplanchna varies considerabley; see - plates of plankton successions. g) Brachionus one of the commonest members of class Rotatoria was frquently found in abundance into the ponds, and we notice an important biological change produce by the rotifer Brachonus colyciflorus: the occurence of its Brachionus clayciflorus forms pallas, is rare in Brazil, as we know about this. h) When we found the water flea MOinodaphnia we do not record simultanous presence of the blue algae Agmenellun (= Merismopedia).

Expansió accelerada de l’univers i teories de gravetat modificada a grans escales

Estudi realitzat a partir d’una estada al Physics Department de la New York University, United States, Estats Units, entre 2006 i 2008. Una de les observacions de més impacte en la cosmologia moderna ha estat la determinació empírica que l’Univers es troba actualment en una fase d’Expansió Accelerada (EA). Aquest fenòmen implica que o bé l’Univers està dominat per un nou sector de matèria/energia, o bé la Relativitat General deixa de tenir validesa a escales cosmològiques. La primera possibilitat comprèn els models d’Energia Fosca (EF), i el seu principal problema és que l’EF ha de tenir propietats tan especials que es fan difícils de justificar teòricament. La segona possibilitat requereix la construcció de teories consistents de Gravetat Modificada a Grans Distàncies (GMGD), que són una generalització dels models de gravetat massiva. L’interès fenomenològic per aquestes teories també va resorgir amb l’aparició dels primers exemples de models de GMGD, com ara el model de Dvali, Gabadadze i Porrati (DGP), que consisteix en un tipus de brana en una dimensió extra. Malauradament, però, aquest model no permet explicar de forma consistent l’EA de l’Univers. Un dels objectius d’aquest projecte ha estat establir la viabilitat interna i fenomenològica dels models de GMGD. Des del punt de vista fenomenològic, ens hem centrat en la questió més important a la pràctica: trobar signatures observacionals que permetin distingir els models de GMGD dels d’EF. A nivell més teòric, també hem investigat el significat de les inestabilitats del model DGP.L’altre gran objectiu que ens vam proposar va ser la construcció de noves teories de GMGD. En la segona part d’aquest projecte, hem elaborat i mostrat la consistència del model “DGP en Cascada”, que generalitza el model DGP a més dimensions extra, i representa el segon model consistent i invariant-Lorentz a l’espai pla conegut. L’existència d’altres models de GMGD més enllà de DGP és de gran interès atès que podria permetre obtenir l’EA de l’Univers de forma purament geomètrica.

Estudi de la degradació anaeròbia de tres contaminants emergents: àcid clofíbric, carbamazepina i ibuprofè

En el present estudi s’ha fet un seguiment baromètric de la producció de biogàs de tres compostos farmacèutics mitjançant tests de degradació anaeròbia. El llot del digestor anaerobi de l’estació depuradora d’aigües residuals (EDAR) de Granollers s’ha emprat com a inòcul. En un primer experiment, s’ha fet l’estudi de l’etapa metanogènica, amb metanol com a substrat i les concentracions de 5, 10 i 20 mg·L-1 d’àcid clofíbric (CLOFI, regulador lípid), ibuprofè (IBU, anti-inflamatori) i carbamazepina (CARBA, antiepilèptic/analgèsic). En un segon experiment, s’ha estudiat l’etapa acetogènica, amb àcid propiònic com a substrat i amb concentracions de 20 i 100 mg·L-1 dels mateixos fàrmacs. Per una banda, en el primer experiment, no s’ha observat degradació dels fàrmacs i cap d’ells presenta toxicitat pel llot anaerobi. CARBA i IBU s’adsorbeixen majoritàriament a la fase sòlida. Per altra banda, en l’etapa acetogènica ni CARBA ni IBU s’han degradat i tampoc presenten toxicitat en cap de les concentracions provades. Com en el cas anterior, la majoria d’aquests fàrmacs queda adsorbit en el llot. En canvi, CLOFI es degrada en 100 mg·L-1 de concentració donant com a producte intermedi un metabòlit.

Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

L'aprenentatge basat en problemes (PBL) en la regulació del metabolisme. Desenvolupament del portal per a l'intercanvi d'experiències en PBL en ciències biomèdiques

L’aprenentatge basat en problemes està en fase experimental en tot el món i és objecte d’anàlisi i reflexió en moltes reunions internacionals. Tanmateix, no hi ha massa feina feta en aquesta direcció en el nostre camp més proper. Hem elaborat problemes per l’aprenentatge de la Regulació del Metabolisme i els hem incorporat a un porta virtual (http://www.ub.edu/GID-BBM). La finalitat d’aquesta estratègia és que mitjançant l’aprenentatge basat en problemes reals o simulacions de problemes reals s’aconsegueixi motivar l’alumnat a treballar de forma continuada durant tot el curs. La millora dels resultats acadèmics haurà de ser la conseqüència lògica d’aquest treball. La finalitat última del projecte que hem desenvolupat és preparar l’alumnat per la seva futura activitat professional a on serà molt important i valorat la seva capacitat de resposta davant de diferents problemes

How multiple repetitions influence the processing of self-, famous and unknown names and faces: an ERP study.

Because we live in an extremely complex social environment, people require the ability to memorize hundreds or thousands of social stimuli. The aim of this study was to investigate the effect of multiple repetitions on the processing of names and faces varying in terms of pre-experimental familiarity. We measured both behavioral and electrophysiological responses to self-, famous and unknown names and faces in three phases of the experiment (in every phase, each type of stimuli was repeated a pre-determined number of times). We found that the negative brain potential in posterior scalp sites observed approximately 170 ms after the stimulus onset (N170) was insensitive to pre-experimental familiarity but showed slight enhancement with each repetition. The negative wave in the inferior-temporal regions observed at approximately 250 ms (N250) was affected by both pre-experimental (famous>unknown) and intra-experimental familiarity (the more repetitions, the larger N250). In addition, N170 and N250 for names were larger in the left inferior-temporal region, whereas right-hemispheric or bilateral patterns of activity for faces were observed. The subsequent presentations of famous and unknown names and faces were also associated with higher amplitudes of the positive waveform in the central-parietal sites analyzed in the 320-900 ms time-window (P300). In contrast, P300 remained unchanged after the subsequent presentations of self-name and self-face. Moreover, the P300 for unknown faces grew more quickly than for unknown names. The latter suggests that the process of learning faces is more effective than learning names, possibly because faces carry more semantic information.

Expression and function of beta1 integrins on human eosinophils

Eosinophils preferentially accumulate at sites of chronic allergic diseases such as bronchial asthma. The mechanisms by which selective eosinophil migration occurs are not fully understood. However, interactions of cell-surface adhesion molecules on the eosinophil with molecular counterligands on endothelial and epithelial cells, and on extracellular matrix proteins, are likely to be critical during the recruitment process. One possible mechanism for selective eosinophil recruitment involves the alpha4beta 1 (VLA-4) integrin which is not expressed on neutrophils. Correlations have been found between infiltration of eosinophils and endothelial expression of VCAM-1, the ligand for VLA-4, in the lungs of asthmatic individuals as well as in late phase reactions in the lungs, nose and skin. Epithelial and endothelial cells respond to the Th2-type cytokines IL-4 and IL-13 with selective de novo expression of VCAM-1, consistent with the possible role of VCAM-1/VLA-4 interactions in eosinophil influx during allergic inflammation. Both beta 1 and beta 2 integrins on eosinophils exist in a state of partial activation. For example, eosinophils can be maximally activated for adhesion to VCAM-1 or fibronectin after exposure to beta 1 integrin-activating antibodies or divalent cations, conditions that do not necessarily affect the total cell surface expression of beta 1 integrins. In contrast, cytokines like IL-5 prevent beta 1 integrin activation while promoting beta 2 integrin function. Furthermore, ligation of integrins can regulate the effector functions of the cell. For example, eosinophil adhesion via beta 1 and/or beta 2 integrins has been shown to alter a variety of functional responses including degranulation and apoptosis. Thus, integrins appear to be important in mediating eosinophil migration and activation in allergic inflammation. Strategies that interfere with these processes may prove to be useful for treatment of allergic diseases.

Physiology and transcriptome of the polycyclic aromatic hydrocarbon-degrading Sphingomonas sp. LH128 after long-term starvation.

The survival, physiology and gene expression profile of the phenanthrene-degrading Sphingomonas sp. LH128 was examined after an extended period of complete nutrient starvation and compared with a non-starved population that had been harvested in exponential phase. After 6 months of starvation in an isotonic solution, only 5 % of the initial population formed culturable cells. Microscopic observation of GFP fluorescent cells, however, suggested that a larger fraction of cells (up to 80 %) were still alive and apparently had entered a viable but non-culturable (VBNC) state. The strain displayed several cellular and genetic adaptive strategies to survive long-term starvation. Flow cytometry, microscopic observation and fatty acid methyl ester (FAME) analysis showed a reduction in cell size, a change in cell shape and an increase in the degree of membrane fatty acid saturation. Transcriptome analysis showed decreased expression of genes involved in ribosomal protein biosynthesis, chromosomal replication, cell division and aromatic catabolism, increased expression of genes involved in regulation of gene expression and efflux systems, genetic translocations, and degradation of rRNA and fatty acids. Those phenotypic and transcriptomic changes were not observed after 4 h of starvation. Despite the starvation situation, the polycyclic aromatic hydrocarbon (PAH) catabolic activity was immediate upon exposure to phenanthrene. We conclude that a large fraction of cells maintain viability after an extended period of starvation apparently due to tuning the expression of a wide variety of cellular processes. Due to these survival attributes, bacteria of the genus Sphingomonas, like strain LH128, could be considered as suitable targets for use in remediation of nutrient-poor PAH-contaminated environments.

Regulation of horizontal gene transfer of the catabolic island ICEclc

ICEclc is a mobile genetic element found in two copies on the chromosome of the bacterium Pseudomonas knackmussii B13. ICEclc harbors genes encoding metabolic pathways for the degradation of chlorocatechols (CLC) and 2-aminophenol (2AP). At low frequencies, ICEclc excises from the chromosome, closes into a circular DNA molecule which can transfer to another bacterium via conjugation. Once in the recipient cell, ICEclc can reintegrate into the chromosome by site-specific recombination. This thesis aimed at identifying the regulatory network underlying the decisions for ICEclc horizontal transfer (HGT). The first chapter is an introduction on integrative and conjugative elements (ICEs) more in general, of which ICEclc is one example. In particular I emphasized the current knowledge of regulation and conjugation machineries of the different classes of ICE. In the second chapter, I describe a transcriptional analysis using microarrays and other experiments to understand expression of ICEclc in exponential and stationary phase. By overlaying transcriptomic profiles with Northern hybridizations and RT- PCR data, we established a transcription map for the entire core region of ICEclc, a region assumed to encode the ICE conjugation process. We also demonstrated how transcription of the ICEclc core is maximal in stationary phase, which correlates to expression of reporter genes fused to key ICEclc promoters. In the third chapter, I present a transcriptome analysis of ICEclc in a variety of different host species, in order to explore whether there are species-specific differences. In the fourth chapter, I focus on the role of a curious ICEclc-encoded TetR-type transcriptional repressor. We find that this gene, which we name mfsR, not only controls its own expression but that of a set of genes for a putative multi-drug efflux pump (mfsABC) as well. By using a combination of biochemical and molecular biology techniques, I could show that MfsR specifically binds to operator boxes in two ICEclc promoters (PmfsR and PmfsA), inhibiting the transcription of both the mfsR and mfsABC-orf38184 operons. Although we could not detect a clear phenotype of an mfsABC deletion, we discuss the implications of pump gene reorganizations in ICEclc and close relatives. In the fifth chapter, we find that mfsR not only controls its own expression and that of the mfsABC operon, but is also indirectly controlling ICEclc transfer. Using gene deletions, microarrays, transfer assays and microscopy-based reporter fusions, we demonstrate that mfsR actually controls a small operon of three regulatory genes. The last gene of this mfsR operon, orf17162, encodes a LysR-type activator that when deleted strongly impairs ICEclc transfer. Interestingly, deletion of mfsR leads to transfer competence in almost all cells, thereby overruling the bistability process in the wild-type. In the final sixth chapter, I discuss the relevance of the present thesis and the resulting perspectives for future studies.

Optimization of spatial resolution for peripheral magnetic resonance angiography.

RATIONALE AND OBJECTIVES: To determine optimum spatial resolution when imaging peripheral arteries with magnetic resonance angiography (MRA). MATERIALS AND METHODS: Eight vessel diameters ranging from 1.0 to 8.0 mm were simulated in a vascular phantom. A total of 40 three-dimensional flash MRA sequences were acquired with incremental variations of fields of view, matrix size, and slice thickness. The accurately known eight diameters were combined pairwise to generate 22 "exact" degrees of stenosis ranging from 42% to 87%. Then, the diameters were measured in the MRA images by three independent observers and with quantitative angiography (QA) software and used to compute the degrees of stenosis corresponding to the 22 "exact" ones. The accuracy and reproducibility of vessel diameter measurements and stenosis calculations were assessed for vessel size ranging from 6 to 8 mm (iliac artery), 4 to 5 mm (femoro-popliteal arteries), and 1 to 3 mm (infrapopliteal arteries). Maximum pixel dimension and slice thickness to obtain a mean error in stenosis evaluation of less than 10% were determined by linear regression analysis. RESULTS: Mean errors on stenosis quantification were 8.8% +/- 6.3% for 6- to 8-mm vessels, 15.5% +/- 8.2% for 4- to 5-mm vessels, and 18.9% +/- 7.5% for 1- to 3-mm vessels. Mean errors on stenosis calculation were 12.3% +/- 8.2% for observers and 11.4% +/- 15.1% for QA software (P = .0342). To evaluate stenosis with a mean error of less than 10%, maximum pixel surface, the pixel size in the phase direction, and the slice thickness should be less than 1.56 mm2, 1.34 mm, 1.70 mm, respectively (voxel size 2.65 mm3) for 6- to 8-mm vessels; 1.31 mm2, 1.10 mm, 1.34 mm (voxel size 1.76 mm3), for 4- to 5-mm vessels; and 1.17 mm2, 0.90 mm, 0.9 mm (voxel size 1.05 mm3) for 1- to 3-mm vessels. CONCLUSION: Higher spatial resolution than currently used should be selected for imaging peripheral vessels.

Phenotypic and molecular characterization of proliferating and differentiated GnRH-expressing GnV-3 cells.

GnRH neurons provide the primary driving force upon the neuroendocrine reproductive axis. Here we used GnV-3 cells, a model of conditionally immortalized GnRH-expressing neurons, to perform an analysis of cell cycle and compare the gene expression profile of proliferating cells with differentiated cells. In the proliferation medium, 45 ± 1.5% of GnV-3 cells are in S-phase by FACS analysis. In the differentiation medium, only 9 ± 0.9% of them are in S-phase, and they acquire the characteristic bipolar shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells in the differentiated state exhibit electrophysiological properties characteristic of neurons. Transcriptomic analysis identified up-regulation of 1931 genes and down-regulation of 1270 genes in cells grown in the differentiation medium compared to cells in the proliferation medium. Subsequent gene ontology study indicated that genes over-expressed in proliferating GnV-3 cells were mainly involved in cell cycle regulations, whereas genes over-expressed in differentiated cells were mainly involved in processes of differentiation, neurogenesis and neuronal morphogenesis. Taken together, these data demonstrate the occurrence of morphological and physiological changes in GnV-3 cells between the proliferating and the differentiated state. Moreover, the genes differentially regulated between these two different states are providing novel pathways potentially important for a better understanding of the physiology of mature GnRH neurons.

TFC de base de dades relacionals

El projecte consisteix en crear un disseny de base de dades segons els requeriments del client, en aquest cas la comunitat Europea, que emmagatzemi les dades de la futura aplicació que gestionarà les votacions ciutadanes. A més del disseny de la base de dades, el projecte haurà d'incorporar una sèrie de processos que consultin dades que podran ser demanades pel programari que faci la interacció amb els usuaris. Programari que no està inclòs en aquesta fase del pla de la Comunitat Europea.

Aganirsen Antisense Oligonucleotide Eye Drops Inhibit Keratitis-Induced Corneal Neovascularization and Reduce Need for Transplantation: The I-CAN Study.

OBJECTIVE: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. DESIGN: Multicenter, double-masked, randomized, placebo-controlled phase III study. PARTICIPANTS: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. MAIN OUTCOME MEASURES: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. RESULTS: Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. CONCLUSIONS: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.

Esquema criptogràfic per exàmens electrònics segurs

Si tota la formació es fa a distància, per què els exàmens en aquest tipus d'ensenyament no ho són? Probablement hi hauran diverses visions a l'hora de respondre aquesta pregunta. En tot cas, per poc que pensem en la realització d'exàmens a distància ens sorgeixen un seguit de qüestions per resoldre: com podem assegurar l'autenticitat i integritat de les dades? Com podem estar segurs que la persona que fa l'examen és qui diu ser? En aquest projecte de final de carrera s'ha dissenyat, implementat i provat un sistema que, mitjançant criptografia de clau pública, garanteix la correcció en totes les fases d'un procés d'examen electrònic. Entenem que aquest és un pas previ a la realització d'exàmens a distància.

Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.

PURPOSE: Ipilimumab is a monoclonal antibody that blocks the immune-inhibitory interaction between CTL antigen 4 (CTLA-4) and its ligands on T cells. Clinical trials in cancer patients with ipilimumab have shown promising antitumor activity, particularly in patients with advanced melanoma. Often, tumor regressions in these patients are correlated with immune-related side effects such as dermatitis, enterocolitis, and hypophysitis. Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known. EXPERIMENTAL DESIGN: We enrolled patients with advanced melanoma in a phase II study with ipilimumab. One of these patients experienced a complete remission of his tumor. The specificity and functional properties of CD8-positive T cells in his peripheral blood, in regressing tumor tissue, and at the site of an immune-mediated skin rash were investigated. RESULTS: Regressing tumor tissue was infiltrated with CD8-positive T cells, a high proportion of which were specific for Melan-A. The skin rash was similarly infiltrated with Melan-A-specific CD8-positive T cells, and a dramatic (>30-fold) increase in Melan-A-specific CD8-positive T cells was apparent in peripheral blood. These cells had an effector phenotype and lysed Melan-A-expressing tumor cells. CONCLUSIONS: Our results show that Melan-A may be a major target for both the autoimmune and antitumor reactions in patients treated with anti-CTLA-4, and describe for the first time the antigen specificity of CD8-positive T cells that mediate tumor rejection in a patient undergoing treatment with an anti-CTLA-4 antibody. These findings may allow a better integration of ipilimumab into other forms of immunotherapy.