Constant regulation for stable CD8 T-cell functional avidity and its possible implications for cancer immunotherapy.

The functional avidity (FA) of cytotoxic CD8 T cells impacts strongly on their functional capabilities and correlates with protection from infection and cancer. FA depends on TCR affinity, downstream signaling strength, and TCR affinity-independent parameters of the immune synapse, such as costimulatory and inhibitory receptors. The functional impact of coreceptors on FA remains to be fully elucidated. Despite its importance, FA is infrequently assessed and incompletely understood. There is currently no consensus as to whether FA can be enhanced by optimized vaccine dose or boosting schedule. Recent findings suggest that FA is remarkably stable in vivo, possibly due to continued signaling modulation of critical receptors in the immune synapse. In this review, we provide an overview of the current knowledge and hypothesize that in vivo, codominant T cells constantly "equalize" their FA for similar function. We present a new model of constant FA regulation, and discuss practical implications for T-cell-based cancer immunotherapy

[multi’vocal]: reflections on engaging everyday people in the development of a collective non-binary synthesized voice

The growing field of Human-Computer Interaction (HCI) takes a step out from conventional screenbased interactions, creating new scenarios, in which voice synthesis and voice recognition become important elements. Such voices are commonly created through concatenative or parametric synthesis methods, which access large voice corpora, pre-recorded by a single professional voice actor. These designed voices arguably propagate representations of gender binary identities. In this paper we present our project, [multi’vocal], which aims to challenge the current gender binary representations in synthesized voices. More specifically we explore if it is possible to create a non-binary synthesized voice through engaging everyday people of diverse backgrounds in giving voice to a collective synthesized voice of all genders, ages and accents

MAGE-A protein and MAGE-A10 gene expressions in liver metastasis in patients with stomach cancer

Tumour samples from 71 patients with stomach cancer, 41 patients with liver metastasis (group A) and 15 patients each in stages II–IV (group B) and stage I (group C) without liver metastasis were analysed. MAGE-A protein expression was evaluated by immunohistochemistry using a 6C1 monoclonal antibody and MAGE-A10 mRNA expression was detected by highly sensitive in situ hybridisation using a cRNA probe. Expressions of MAGE-A protein and MAGE-A10 mRNA in group A were detected in 65.9 and 80.5%, respectively. Both protein and gene showed significantly higher expression in group A than those in groups B (6.7, 26.7%) and C (0, 0%) (P=0.0003, P=<0.0001, respectively). MAGE-A10 mRNA expression in liver metastasis was found in eight (88.9%) out of nine patients. The concordant rate between MAGE-A family protein expression and MAGE-A10 mRNA expression in the primary sites was 81.7% (P<0.0001). MAGE-A10 gene expression was associated with reduced survival duration. The results of this study suggest that MAGE-A10 is a possible target in active immunotherapy for advanced stomach cancer

Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Laboratory assays are needed for early stage non-small lung cancer (NSCLC) that can link molecular and clinical heterogeneity to predict relapse after surgical resection. We technically validated two miRNA assays for prediction of relapse in NSCLC. Total RNA from seventy-five formalin-fixed and paraffin-embedded (FFPE) specimens was extracted, labeled and hybridized to Affymetrix miRNA arrays using different RNA input amounts, ATP-mix dilutions, array lots and RNA extraction- and labeling methods in a total of 166 hybridizations. Two combinations of RNA extraction- and labeling methods (assays I and II) were applied to a cohort of 68 early stage NSCLC patients.</p> <p>Results</p> <p>RNA input amount and RNA extraction- and labeling methods affected signal intensity and the number of detected probes and probe sets, and caused large variation, whereas different ATP-mix dilutions and array lots did not. Leave-one-out accuracies for prediction of relapse were 63% and 73% for the two assays. Prognosticator calls ("no recurrence" or "recurrence") were consistent, independent on RNA amount, ATP-mix dilution, array lots and RNA extraction method. The calls were not robust to changes in labeling method.</p> <p>Conclusions</p> <p>In this study, we demonstrate that some analytical conditions such as RNA extraction- and labeling methods are important for the variation in assay performance whereas others are not. Thus, careful optimization that address all analytical steps and variables can improve the accuracy of prediction and facilitate the introduction of microRNA arrays in the clinic for prediction of relapse in stage I non-small cell lung cancer (NSCLC).</p

Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine whether EBV seropositive patients with lung cancer have an altered virus-specific CTL response, as compared to age-matched healthy controls and whether any variation in this response could be attributed to senescence.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells from lung cancer patients, age-matched and younger healthy individuals were used to measure EBV-specific CTLs after in vitro amplification with the GLCTLVAML and RYSIFFDYM peptides followed by HLA-multimer staining.</p> <p>Results</p> <p>Lung cancer patients and aged-matched controls had significantly lesser EBV-specific CTL than younger healthy individuals. Multimer positive populations from either group did not differ with respect to the percentage of multimer positive CTLs and the intensity of multimer binding.</p> <p>Conclusions</p> <p>This study provides evidence that patients with lung cancer exhibit an EBV-specific CTL response equivalent to that of age-matched healthy counterparts. These data warrant the examination of whether young individuals have a more robust anti-tumor response, as is the case with the anti-EBV response.</p

Influence of microclimate and geomorphological factors on alpine vegetation in the Western Swiss Alps

Among the numerous environmental factors affecting plant communities in alpine ecosystems, the influence of geomorphic processes and landforms has been minimally investigated. Subjected to persistent climate warming, it is vital to understand how these factors affect vegetation properties. Here, we studied 72 vegetation plots across three sites located in the Western Swiss Alps, characterized by high geomorphological variability and plant diversity. For each plot, vascular plant species were inventoried and ground surface temperature, soil moisture, topographic variables, earth surface processes (ESPs) and landform morphodynamics were assessed. The relationships between plant communities and environmental variables were analysed using non-metric multidimensional scaling (NMDS) and multivariate regression techniques (generalized linear model, GLM, and generalized additive model, GAM). Landform morphodynamics, growing degree days (sum of degree days above 5°C) and mean ground surface temperature were the most important explanatory variables of plant community composition. Furthermore, the regression models for species cover and species richness were significantly improved by adding a morphodynamics variable. This study provides complementary support that landform morphodynamics is a key factor, combined with growing degree days, to explain alpine plant distribution and community composition

A collaborative artefact reconstruction environment

A novel collaborative artefact reconstruction environment design is presented that is informed by experimental task observation and participatory design. The motivation for the design was to enable collaborative human and computer effort in the reconstruction of fragmented cuneiform tablets: millennia-old clay tablets used for written communication in early human civilisation. Thousands of joining cuneiform tablet fragments are distributed within and between worldwide collections. The reconstruction of the tablets poses a complex 3D jigsaw puzzle with no physically tractable solution. In reconstruction experiments, participants collaborated synchronously and asynchronously on virtual and physical reconstruction tasks. Results are presented that demonstrate the difficulties experienced by human reconstructors in virtual tasks compared to physical tasks. Unlike computer counterparts, humans have difficulty identifying joins in virtual environments but, unlike computers, humans are averse to making incorrect joins. A successful reconstruction environment would marry the opposing strengths and weaknesses of humans and computers, and provide tools to support the communications and interactions of successful physical performance, in the virtual setting. The paper presents a taxonomy of the communications and interactions observed in successful physical and synchronous collaborative reconstruction tasks. Tools for the support of these communications and interactions were successfully incorporated in the “i3D” virtual environment design presented

Physicochemical Characterization of Passive Films and Corrosion Layers by Differential Admittance and Photocurrent Spectroscopy

Two different electrochemical techniques, differential admittance and photocurrent spectroscopy, for the characterization of electronic and solid state properties of passive films and corrosion layers are described and critically evaluated. In order to get information on the electronic properties of passive film and corrosion layers as well as the necessary information to locate the characteristic energy levels of the passive film/electrolyte junction like: flat band potential (Ufb), conduction band edge (EC) or valence band edge (EV), a wide use of Mott-Schottky plots is usually reported in corrosion science and passivity studies. It has been shown, in several papers, that the use of simple M-S theory to get information on the electronic properties and energy levels location at the film/electrolyte interface can be seriously misleading and/or conflicting with the physical basis underlying the M-S theory. A critical appraisal of this approach to the study of very thin and thick anodic passive film grown on base-metals (Cr, Ni, Fe, SS etc..) or on valve metals (Ta, Nb, W etc..) is reported in this work, together with possible alternative approach to overcome some of the mentioned inconsistencies. At this aim the theory of amorphous semiconductor Schottky barrier, introduced several years ago in the study of passive film/electrolyte junction, is reviewed by taking into account some of the more recent results obtained by the present authors. Future developments of the theory appears necessary to get more exact quantitative information on the electronic properties of passive films, specially in the case of very thin film like those formed on base metals and their alloys. The second technique described in this chapter, devoted to the physico-chemical characterization of passive film and corrosion layers, is a more recent technique based on the analysis of the photo-electrochemical answer of passive film/electrolyte junction under illumination with photons having suitable energy. Such a technique usually referred to as Photocurrent Spectroscopy (PCS) has been developed on the basis of the large research effort carried out by several groups in the 1970’s and aimed to investigate the possible conversion of solar energy by means of electrochemical cells. In this work the fundamentals of semiconductor/electrolyte junctions under illumination will be highlighted both for crystalline and amorphous materials. The role of amorphous nature and film thickness on the photo-electrochemical answer of passive film/solution interface is reviewed as well the use of PCS for quantitative analysis of the film composition based on a semi-empirical correlation between optical band gap and difference of electronegativity of film constituents previously suggested by the present authors. In this frame the results of PCS studies on valve metal oxides and valve metal mixed oxides will be discussed in order to show the validity of the proposed method. The results of PCS studies aimed to get information on passive film composition and carried out by different authors on base metals (Fe, Cr, Ni) and their alloys, including stainless steel, will be also compared with compositional analysis carried out by well-established surface analysis techniques