Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.

Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.

Reading Ng Kim Chew: Malaysian-Chineseness and memory in contemporary Malaysian Chinese literature in taiwan

The idea of Chineseness as a geographic, cultural-specific and ethnically-charged concept, and the pivotal role assumed by memory linger throughout the writings of most authors hailing from Chinese community in Southeast Asia. Among these communities, being the Malaysian Chinese the more prolific in terms of number of writers and pieces of literature produced, this paper deals specifically with it. Its focus is put on the literature produced by Malaysian Chinese authors residing in Taiwan, which topic constitutes an important part of the first chapter, and on one of its main representatives, Ng Kim Chew, to whom chapter two and three are fully dedicated. A literary analysis of one of his short stories, Huo yu tu, will allow the reader to have a first-hand experience, through excerpts from the original text, of the importance of Chineseness and memory in the literary production of Ng and of many authors sharing with him similar life and literary experiences. I started this research from the assumption that these authors make large use of their own memories and memories from their own community in their writing as a way to re-tie themselves to the Chineseness they left in their places of origin. However in the case of Ng Kim Chew, the analysis of his works led be to theorizing that the identity he is imbued with, if there is one, is not Chinese, nor Malaysian, but purely and distinctively Malaysian-Chinese. This paper can also serve as an introduction for the general public to the field of Sinophone literature from Southeast Asia and to promote wider and innovative paths of research within the realm of Chinese studies that go beyond China proper.

Analyzing the effects of transient faults into applications

As computer chips implementation technologies evolve to obtain more performance, those computer chips are using smaller components, with bigger density of transistors and working with lower power voltages. All these factors turn the computer chips less robust and increase the probability of a transient fault. Transient faults may occur once and never more happen the same way in a computer system lifetime. There are distinct consequences when a transient fault occurs: the operating system might abort the execution if the change produced by the fault is detected by bad behavior of the application, but the biggest risk is that the fault produces an undetected data corruption that modifies the application final result without warnings (for example a bit flip in some crucial data). With the objective of researching transient faults in computer system’s processor registers and memory we have developed an extension of HP’s and AMD joint full system simulation environment, named COTSon. This extension allows the injection of faults that change a single bit in processor registers and memory of the simulated computer. The developed fault injection system makes it possible to: evaluate the effects of single bit flip transient faults in an application, analyze an application robustness against single bit flip transient faults and validate fault detection mechanism and strategies.

Heterogeneous dynamics, aggregation and the persistence of economic shocks

It has been recently emphasized that, if individuals have heterogeneous dynamics, estimates of shock persistence based on aggregate data are significatively higher than those derived from its disaggregate counterpart. However, a careful examination of the implications of this statement on the various tools routinely employed to measure persistence is missing in the literature. This paper formally examines this issue. We consider a disaggregate linear model with heterogeneous dynamics and compare the values of several measures of persistence across aggregation levels. Interestingly, we show that the average persistence of aggregate shocks, as measured by the impulse response function (IRF) of the aggregate model or by the average of the individual IRFs, is identical on all horizons. This result remains true even in situations where the units are (short-memory) stationary but the aggregate process is long-memory or even nonstationary. In contrast, other popular persistence measures, such as the sum of the autoregressive coefficients or the largest autoregressive root, tend to be higher the higher the aggregation level. We argue, however, that this should be seen more as an undesirable property of these measures than as evidence of different average persistence across aggregation levels. The results are illustrated in an application using U.S. inflation data.

Tocant totes les tecles: Vicenç Sabater, un obrer de la música

Treball de recerca realitzat per un alumne d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit cientí­fic del Jovent l'any 2009. El treball tracta sobre la petita memòria històrica en la faceta de l'oci de la nostra societat , el ball i la música concretament, centrat en la memòria de l'avi de l'autor, músic, arranjador i compositor. Es tracta doncs, d'una investigació sobre la música de ball a Barcelona i a Catalunya, i en general també a Europa, atès que gràcies a les vivències d'en Vicenç Sabater (l'avi), es relata com era la seva feina i el seu ofici, el de músic. La recerca està ordenada cronològicament, començant pel seu naixement (1930), la formació i les primeres actuacions, passant per tota la seva vida personal, però sobretot professional, i conclou amb un epíleg sense el qual el treball de recerca no tindria sentit, ja que aquest explica com el Vicenç no s'ha jubilat mai, perquè sempre ha estat treballant amb la música, i perquè sempre que el seu físic li permeti, ell s'hi seguirà dedicant. El treball inclou un apartat destacat de la llarga etapa (30 anys) de Sabater amb el grup musical 'Rudy Ventura y su conjunto'. Molta d'aquesta informació s'obté a través d'entrevistes a dos dels cinc integrants del grup: el mateix Jaume Ventura, i en Joan Antoni Calvet, cantant i bateria, respectivament. Apartat que, dissortadament, s'ha convertit en el meu involuntari i modest homenatge a Jaume ('Rudy') Ventura , recentment traspassat.

Halipegus dubius Klein, 1905 (Trematoda, Hemiuridae): a redescription, with notes on the working of the ovarian complex

A redescription of Halipegus dubius Klein, 1905, of Brazilian frogs Leptodactylus pentadactylus and L. ocellatus, is presented. The parasite was found exclusively in the buccal cavity, in number varying from 1 (in most instances) to 3, and exceptionally 25 (one instance). Morphological data were based on 40 whole-mounted specimens and 4 serially sectioned ones. Larval development takes place in planorbid snails (Biomphalaria glabrata and B. tenagophila) and in an undetermined species of cyclops. Working of the ovarian complex was followed by microscopical observation of life specimens. Constrating with the similarity of the four American species of Halipegus currently recognized as valid, they can be easily separated by the characters of their cercariae.

Aplicación para la gestión de un sistema de incidencias de un almacén robotizado

Aquest projecte té com objectiu fer un sistema d’incidències pel control d’un magatzem robotitzat i del cost que comporta la resolució d’aquestes. D’aquesta manera es pretén canviar un mètode de treball rudimentari, passant a un altre totalment estructurat que serveixi per millorar el actual. Per això s’ha creat una aplicació basada en la tecnologia JSF, què permet aconseguir els nostres objectius. L’aplicació inclou una base de dades feta en PostGres SQL on es guardarà tota la informació que s’utilitza en la nostra aplicació. En aquesta memòria s’ha volgut explicar quins han estat els diferents passos que es van donar per poder assolir tots els nostres objectius. En la primera part realitzem una introducció a la situació del problema que es vol solucionar i descriurem els objectius que en hem marcat. Seguidament s’analitzen els requeriments i es detalla com s’implementen les diferents parts de l’aplicació. Per acabar parlem sobre el procés de testing realitzat que ens assegura el correcte funcionament del programa. Resumint, el objectiu principal d’aquest projecte consisteix en crear una eina que a la vegada que facilita la feina dels treballadors del magatzem, serveixi per al control de tot el sistema de treball als directius de l’empresa.

Effects of anxiety on visuospatial pattern discrimination and decision-making processes: what can we learn from brain dynamics ?

Detection and discrimination of visuospatial input involve at least extracting, selecting and encoding relevant information and decision-making processes allowing selecting a response. These two operations are altered, respectively, by attentional mechanisms that change discrimination capacities, and by beliefs concerning the likelihood of uncertain events. Information processing is tuned by the attentional level that acts like a filter on perception, while decision-making processes are weighed by subjective probability of risk. In addition, it has been shown that anxiety could affect the detection of unexpected events through the modification of the level of arousal. Consequently, purpose of this study concerns whether and how decision-making and brain dynamics are affected by anxiety. To investigate these questions, the performance of women with either a high (12) or a low (12) STAI-T (State-Trait Anxiety Inventory, Spielberger, 1983) was examined in a decision-making visuospatial task where subjects have to recognize a target visual pattern from non-target patterns. The target pattern was a schematic image of furniture arranged in such a way as to give the impression of a living room. Non-target patterns were created by either the compression or the dilatation of the distances between objects. Target and non-target patterns were always presented in the same configuration. Preliminary behavioral results show no group difference in reaction time. In addition, visuo-spatial abilities were analyzed trough the signal detection theory for quantifying perceptual decisions in the presence of uncertainty (Green and Swets, 1966). This theory treats detection of a stimulus as a decision-making process determined by the nature of the stimulus and cognitive factors. Astonishingly, no difference in d' (corresponding to the distance between means of the distributions) and c (corresponds to the likelihood ratio) indexes was observed. Comparison of Event-related potentials (ERP) reveals that brain dynamics differ according to anxiety. It shows differences in component latencies, particularly a delay in anxious subjects over posterior electrode sites. However, these differences are compensated during later components by shorter latencies in anxious subjects compared to non-anxious one. These inverted effects seem indicate that the absence of difference in reaction time rely on a compensation of attentional level that tunes cortical activation in anxious subjects, but they have to hammer away to maintain performance.

Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor.

Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma. Their in vivo expansion is often observed with advanced disease. In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen. Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma. Interestingly, this population is oligoclonal and displays a clear memory phenotype. However, a detailed study of these cells indicated that they are unlikely to be directly specific for melanoma, so that their in vivo expansion may have been driven by an exogenous antigen. Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen. Finally, we discuss potential perspectives regarding the role of such cells in heterologous immunity, by influencing the balance between protective immunity and pathology, e.g. in the case of melanoma development.

Memory in contracts: the experience of the EBRD (1991-2003)

The objective of this paper is to identify the role of memory as a screening device in repeated contracts with asymmetric information in financial intermediation. We use an original dataset from the European Bank for Reconstruction and Development. We propose a simple empirical method to capture the role of memory using the client's reputation. Our results unambiguously isolate the dominant effect of memory on the bank's lending decisions over market factors in the case of established clients.

A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: The European experience.

BACKGROUND: The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated rejection detailed in the 2004 grading system. METHODS: The hematoxylin-eosin-stained sections of 20 sets of endomyocardial biopsies were pre-selected and graded by two pathologists (A.A. and M.B.) and digitized using a telepathology digital pathology system (Aperio ImageScope System; for details refer to http://aperio.com/). Their diagnoses were considered the index diagnoses, which covered all grades of acute cellular rejection (ACR), early ischemic lesions, Quilty lesions, late ischemic lesions and (in the 2005 system) antibody-mediated rejection (AMR). Eighteen pathologists from 16 heart transplant centers in 7 European countries participated in the study. Inter-observer reproducibility was assessed using Fleiss's kappa and Krippendorff's alpha statistics. RESULTS: The combined kappa value of all grades diagnosed by all 18 pathologists was 0.31 for the 1990 grading system and 0.39 for the 2005 grading system, with alpha statistics at 0.57 and 0.55, respectively. Kappa values by grade for 1990/2005, respectively, were: 0 = 0.52/0.51; 1A/1R = 0.24/0.36; 1B = 0.15; 2 = 0.13; 3A/2R = 0.29/0.29; 3B/3R = 0.13/0.23; and 4 = 0.18. For the 2 cases of AMR, 6 of 18 pathologists correctly suspected AMR on the hematoxylin-eosin slides, whereas, in each of 17 of the 18 AMR-negative cases a small percentage of pathologists (range 5% to 33%) overinterpreted the findings as suggestive for AMR. CONCLUSIONS: Reproducibility studies of cardiac biopsies by pathologists in different centers at the international level were feasible using digitized slides rather than conventional histology glass slides. There was a small improvement in interobserver agreement between pathologists of different European centers when moving from the 1990 ISHLT classification to the "new" 2005 ISHLT classification. Morphologic suspicion of AMR in the 2004 system on hematoxylin-eosin-stained slides only was poor, highlighting the need for better standardization of morphologic criteria for AMR. Ongoing educational programs are needed to ensure standardization of diagnosis of both acute cellular and antibody-mediated rejection.

Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group.

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.

Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation.

Ag-experienced or memory T cells have increased reactivity to recall Ag, and can be distinguished from naive T cells by altered expression of surface markers such as CD44. Memory T cells have a high turnover rate, and CD8(+) memory T cells proliferate upon viral infection, in the presence of IFN-alphabeta and/or IL-15. In this study, we extend these findings by showing that activated NKT cells and superantigen-activated T cells induce extensive bystander proliferation of both CD8(+) and CD4(+) memory T cells. Moreover, proliferation of memory T cells can be induced by an IFN-alphabeta-independent, but IFN-gamma- or IL-12-dependent pathway. In these conditions of bystander activation, proliferating memory (CD44(high)) T cells do not derive from activation of naive (CD44(low)) T cells, but rather from bona fide memory CD44(high) T cells. Together, these data demonstrate that distinct pathways can induce bystander proliferation of memory T cells.