Music-reading expertise modulates the visual span for English letters but not Chinese characters.

Recent research has suggested that the visual span in stimulus identification can be enlarged through perceptual learning. Since both English and music reading involve left-to-right sequential symbol processing, music-reading experience may enhance symbol identification through perceptual learning particularly in the right visual field (RVF). In contrast, as Chinese can be read in all directions, and components of Chinese characters do not consistently form a left-right structure, this hypothesized RVF enhancement effect may be limited in Chinese character identification. To test these hypotheses, here we recruited musicians and nonmusicians who read Chinese as their first language (L1) and English as their second language (L2) to identify music notes, English letters, Chinese characters, and novel symbols (Tibetan letters) presented at different eccentricities and visual field locations on the screen while maintaining central fixation. We found that in English letter identification, significantly more musicians achieved above-chance performance in the center-RVF locations than nonmusicians. This effect was not observed in Chinese character or novel symbol identification. We also found that in music note identification, musicians outperformed nonmusicians in accuracy in the center-RVF condition, consistent with the RVF enhancement effect in the visual span observed in English-letter identification. These results suggest that the modulation of music-reading experience on the visual span for stimulus identification depends on the similarities in the perceptual processes involved

SIMP (Strongly Interacting Massive Particle) Search

We consider laboratory experiments that can detect stable, neutral strongly interacting massive particles (SIMPs). We explore the SIMP annihilation cross section from its minimum value (restricted by cosmological bounds) to the barn range, and vary the mass values from a GeV to a TeV. We also consider the prospects and problems of detecting such particles at the Tevatron.Comment: Latex. 7 pages, 1 eps figure. Proceedings to the 4th UCLA Symposium on Dark Matter DM2000, Marina del Rey, CA, USA, Feb. 23-25, 200

Experimental verification of electrostatic boundary conditions in gate-patterned quantum devices

In a model of a gate-patterned quantum device it is important to choose the correct electrostatic boundary conditions (BCs) in order to match experiment. In this study, we model gated-patterned devices in doped and undoped GaAs heterostructures for a variety of BCs. The best match is obtained for an unconstrained surface between the gates, with a dielectric region above it and a frozen layer of surface charge, together with a very deep back boundary. Experimentally, we find a 0.2V offset in pinch-off characteristics of one-dimensional channels in a doped heterostructure before and after etching off a ZnO overlayer, as predicted by the model. Also, we observe a clear quantised current driven by a surface acoustic wave through a lateral induced n-i-n junction in an undoped heterostructure. In the model, the ability to pump electrons in this type of device is highly sensitive to the back BC. Using the improved boundary conditions, it is straightforward to model quantum devices quite accurately using standard software

A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR

EGFR-specific T cell frequencies correlate with EGFR expression in head and neck squamous cell carcinoma

Background\ud In head and neck squamous cell carcinoma (HNSCC), expression levels of the epidermal growth factor receptor (EGFR) correlate with poor prognosis and decreased survival rates. As the mechanisms responsible for cellular immune response to EGFR in vivo remain unclear, the frequency and function of EGFR-specific cytotoxic T cells (CTL) was determined in HNSCC patients.\ud \ud Methods\ud The frequency of CTL specific for the HLA-A2.1-restricted EGFR-derived YLN peptide (YLNTVQPTCV) and KLF peptide (KLFGTSGQKT) was determined in 16 HLA-A2.1+ HNSCC patients and 16 healthy HLA-A2.1+ individuals (NC) by multicolor flow cytometry. Patients' results were correlated to EGFR expression obtained by immunohistochemistry in corresponding tumor sections. Proliferation and anti-tumor activity of peptide-specific CTL was demonstrated by in vitro stimulation with dendritic cells pulsed with the peptides.\ud \ud Results\ud Frequency of EGFR-specific CTL correlated significantly with EGFR expression in tumor sections (p = 0.02, r2 = 0.6). Patients with elevated EGFR scores (> 7) had a significantly higher frequency of EGFR-specific CTL than NC and patients with low EGFR scores (< 7). EGFR-specific CTL from cancer patients were expanded ex vivo and produced IFN-γ upon recognition of EGFR+ target cells.\ud \ud Conclusion\ud EGFR expressed on HNSCC cells induces a specific immune response in vivo. Strategies for expansion of EGFR-specific CTL may be important for future immunotherapy of HNSCC patients

Galectins as immunoregulators during infectious processes: from microbial invasion to the resolution of the disease

Recent evidence has implicated galectins, a family of evolutionarily conserved carbohydrate-binding proteins, as regulators of immune cell homeostasis and host-pathogen interactions. Galectins operate at different levels of innate and adaptive immune responses, by modulating cell survival and cell activation or by influencing the Th1/Th2 cytokine balance. Furthermore, galectins may contribute to host-pathogen recognition and may serve as receptors for specific interactions of pathogens with their insect vectors. Here we will explore the influence of galectins in immunological processes relevant to microbial infection and will summarize exciting recent work related to the specific interactions between galectins and their glycoconjugate ligands as critical determinants of pathogen recognition. Understanding the role of galectin-sugar interactions during the course of microbial infections might contribute to defining novel targets for disease prevention and immune intervention.Fil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Consumer perceptions of co-branding alliances: Organizational dissimilarity signals and brand fit

This study explores how consumers evaluate co-branding alliances between dissimilar partner firms. Customers are well aware that different firms are behind a co-branded product and observe the partner firms’ characteristics. Drawing on signaling theory, we assert that consumers use organizational characteristics as signals in their assessment of brand fit and for their purchasing decisions. Some organizational signals are beyond the control of the co-branding partners or at least they cannot alter them on short notice. We use a quasi-experimental design and test how co-branding partner dissimilarity affects brand fit perception. The results show that co-branding partner dissimilarity in terms of firm size, industry scope, and country-of-origin image negatively affects brand fit perception. Firm age dissimilarity does not exert significant influence. Because brand fit generally fosters a benevolent consumer attitude towards a co-branding alliance, the findings suggest that high partner dissimilarity may reduce overall co-branding alliance performance

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT

Proline-Rich Tyrosine Kinase 2 (Pyk2) Promotes Cell Motility of Hepatocellular Carcinoma through Induction of Epithelial to Mesenchymal Transition

Aims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun et al.published_or_final_versio