Failing to Connect: Dialogue and Love in E.M. Forster\u27s \u3ci\u3eThe Life to Come\u3c/i\u3e

Upon being informed that a piece of his posthumously published homoerotic literature was being used as a device for reigniting a productive dialogue of love between the gay and the Evangelical Christian, E.M. Forster would assuredly bristle with skepticism and doubt, if not outright disgust. Readers and critics who have reserved an iconic position for Forster in the chronology of gay liberation literature would likely evince a similar knee-jerk reaction. Admittedly, the writer\u27s lifelong tendency to chafe uneasily against what he most often depicted as a doctrine of hypocrisy appears to be an obstacle which precludes utilizing his text The Life to Come as an instructional on breathing fresh air into the relationship between faith and homosexuality. In the face of this considerable set of roadblocks, however, one would be wise to recall the carefully optimistic desire to only connect, a hope posited in the author\u27s novel Howard\u27s End which has now become his defining credo. Forster\u27s bibliography is essentially a meatgrinder running interpersonal connection through its jaws, yet the author could never dismiss human communication\u27s foremost position in his ideology. It was the most direct avenue to love, an area of unlimited potential. The Life to Come, a messy tale on a constant downward spiral, fails to arrive at such a plateau. In fact, the narrative expends its last gasp of energy toppling the emotion. Reading the short story against a collection of theoretical voices highlighted by Terry Eagleton, Mikhail Bakhtin, and Madeline L\u27Engle, The Life to Come\u27s weeds of disintegration may be identified and uprooted. Consequently, praxis for Evangelical Christian action that both honors Forster\u27s reverence for human connection and addresses the present day conflict between faith and homosexuality may be planted

Influence of Menopausal Status on Lipids and Lipoproteins and Fat Mass Distribution: The Pioneer Project

Following menopause, fat redistribution and increased risk for dyslipidemia are common. The influence of menopause; however, on the associations between total and regional fat mass with lipids and lipoproteins remains unclear. PURPOSE: The purpose of this investigation was to determine the influence of menopausal status on associations between total and regional fat mass and lipids and lipoproteins. METHODS: Sedentary, non-smoking women (n=209) were grouped based on current menstrual status: premenopausal (n=143, mean±SD; age=42.7±7.7 yr, BMI=24.5±4.0 kg•m -2, WC=77.4±9.9 cm) or postmenopausal (n=66, mean±SD; age=52.9±5.3 yr, BMI= 24.9±4.2 kg•m -2, WC=78.8±9.9 cm). Fasting (12 hr) serum samples were analyzed for total cholesterol (TC), triglyceride (Tg), LDL-C, HDL-C, HDL2-C, and HDL3-C concentrations. Total (TF), abdominal (AF), hip (HF) and mid-thigh (MTF) fat mass were quantified by DXA. A MANCOVA was used to determine differences between groups for total and regional fat mass and lipids and lipoproteins controlling for HRT status. Stepwise multiple regression analysis was used to determine if menopausal status influenced the association of total and regional fat mass with lipids and lipoproteins. The criterion reference for statistical significance was set at a P \u3c 0.05. RESULTS: Postmenopausal women had significantly greater TC, HDL-C, LDL-C and HDL3-C concentrations than premenopausal women. No significant differences were observed between groups for total and regional fat mass. In premenopausal women, AF predicted TC, but no associations were observed in postmenopausal women. In premenopausal women, AF+HF and AF+TF were significant predictors of Tg and LDL-C, respectively. In contrast, only AF predicted Tg and LDL-C in postmenopausal women. AF+MTF best predicted HDL-C in premenopausal women; however, TF+MTF best predicted HDL-C in postmenopausal women. In premenopausal women, no associations were observed with HDL2-C or HDL3-C. TF and TF+MTF were best predictors of HDL2-C and HDL3-C, respectively in postmenopausal women. CONCLUSION: Menopausal status has an effect on lipid and lipoprotein-cholesterol concentrations, but not on total and regional fat mass. In addition, menopausal status had an influence on the associations of total and regional fat mass with lipids and lipoproteins

Skeletal Light-Scattering Accelerates Bleaching Response in Reef-Building Corals

Background At the forefront of ecosystems adversely affected by climate change, coral reefs are sensitive to anomalously high temperatures which disassociate (bleaching) photosynthetic symbionts (Symbiodinium) from coral hosts and cause increasingly frequent and severe mass mortality events. Susceptibility to bleaching and mortality is variable among corals, and is determined by unknown proportions of environmental history and the synergy of Symbiodinium- and coral-specific properties. Symbiodinium live within host tissues overlaying the coral skeleton, which increases light availability through multiple light-scattering, forming one of the most efficient biological collectors of solar radiation. Light-transport in the upper ~200 μm layer of corals skeletons (measured as ‘microscopic’ reduced-scattering coefficient, μ′S,m), has been identified as a determinant of excess light increase during bleaching and is therefore a potential determinant of the differential rate and severity of bleaching response among coral species. Results Here we experimentally demonstrate (in ten coral species) that, under thermal stress alone or combined thermal and light stress, low-μ′S,m corals bleach at higher rate and severity than high-μ′S,m corals and the Symbiodinium associated with low-μ′S,m corals experience twice the decrease in photochemical efficiency. We further modelled the light absorbed by Symbiodinium due to skeletal-scattering and show that the estimated skeleton-dependent light absorbed by Symbiodinium (per unit of photosynthetic pigment) and the temporal rate of increase in absorbed light during bleaching are several fold higher in low-μ′S,m corals. Conclusions While symbionts associated with low-μ′S,m corals receive less total light from the skeleton, they experience a higher rate of light increase once bleaching is initiated and absorbing bodies are lost; further precipitating the bleaching response. Because microscopic skeletal light-scattering is a robust predictor of light-dependent bleaching among the corals assessed here, this work establishes μ′S,m as one of the key determinants of differential bleaching response

Inference of patient-specific pathway activities from multi-dimensional cancer genomics data using PARADIGM

Motivation: High-throughput data is providing a comprehensive view of the molecular changes in cancer tissues. New technologies allow for the simultaneous genome-wide assay of the state of genome copy number variation, gene expression, DNA methylation and epigenetics of tumor samples and cancer cell lines

The UCSC cancer genomics browser: update 2011

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) comprises a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. The browser displays whole-genome views of genome-wide experimental measurements for multiple samples alongside their associated clinical information. Multiple data sets can be viewed simultaneously as coordinated ‘heatmap tracks’ to compare across studies or different data modalities. Users can order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways and user-contributed collections of genes. Integrated standard statistical tools provide dynamic quantitative analysis within all available data sets. The browser hosts a growing body of publicly available cancer genomics data from a variety of cancer types, including data generated from the Cancer Genome Atlas project. Multiple consortiums use the browser on confidential prepublication data enabled by private installations. Many new features have been added, including the hgMicroscope tumor image viewer, hgSignature for real-time genomic signature evaluation on any browser track, and ‘PARADIGM’ pathway tracks to display integrative pathway activities. The browser is integrated with the UCSC Genome Browser; thus inheriting and integrating the Genome Browser’s rich set of human biology and genetics data that enhances the interpretability of the cancer genomics data

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival