Paint it Black -- A Combinatorial Yawp

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Signal transduction and activator of transcription-3 (STAT3) in patients with colorectal cancer: associations with the phenotypic features of the tumour and host

Purpose: In patients with colorectal cancer (CRC), a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL-6/JAK/STAT3 pathway. The present study examines the relationship between tumour total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses and survival in patients undergoing resection of stage I-III CRC. Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumour cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density and Klintrup-Mäkinen grade) and systemic inflammatory responses and cancer-specific survival were examined. Results: 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r=0.363, P<0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r=0.130, P=0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P=0.012), CD8+ (P=0.003) and FOXP3+ T-lymphocytes (P=0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P=0.004). The combination of nuclear STAT3/pSTAT3 stratified five-year survival from 81% to 62% (P=0.012), however was not associated with survival independent of venous invasion, tumour perforation or tumour budding. Conclusion In patients undergoing CRC resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Up-regulation of tumour STAT3 may be an important mechanism whereby the tumour deregulates local and systemic inflammatory responses

Interstitial chemotherapy with biodegradable BCNU (Gliadel®) wafers in the treatment of malignant gliomas

Malignant gliomas represent the majority of primary brain tumors, and the prognosis of the patients afflicted with these tumors has been historically dismal, with almost uniform progressive neurologic impairment and rapid death. Even with multimodal treatment using surgery, focal radiation, and chemotherapy, no major strides were made until recently. The development of interstitial BCNU wafers (carmustine wafers, Gliadel®) has led to promising results in the treatment of a selected patients with malignant gliomas, as well as with other intracranial malignancies.BCNU is one of the first systemic chemotherapies which had obtained United States Food and Drug Administration (FDA) approval for the treatment of brain tumors. However, systemic use has been hampered by the modest prolongation of survival and by the prolonged myelosuppression and potentially fatal pulmonary toxicity. The development of interstitial therapies with BCNU represented a great step forward, allowing direct delivery to the tumor bed, with virtually no systemic toxicities. Clinical studies of BCNU wafers have showed good efficacy in both newly diagnosed and recurrent gliomas, as well as a possible therapeutic role in other primary or secondary intracranial malignancies. New studies are currently underway trying to improve the efficacy of the BCNU wafers (Gliadel®) by combining them with different systemic chemotherapies. An overview of the current knowledge ranging from the preclinical developments, to the efficacy and safety seen in the clinical trials and in clinical practice following the drug approval to the future avenues of research is therefore timely

Friends-Based Protective Strategies and Unwanted Sexual Experiences: A Daily Diary Examination of First Year College Women

Risk for unwanted sexual experiences can emerge in social contexts—the same contexts that early college women navigate with their friends. Though friends naturally engage in prevention strategies, less is known about how capable guardianship influences risk. Using multilevel structural equation modeling, the present study examined guardianship at the person and situation levels. First-year college women (N = 132) completed eight weekends of daily surveys. We examined whether guardianship (e.g., more friends present, greater proportion of female friends, no intoxicated friends) would reduce unwanted sexual experience risk and if this relation was mediated by friends-based strategy use. An alternative model was also tested with the same predictors, but with unwanted sexual experiences as the mediator and friends-based strategy use as the outcome. Over half (58%) of extended weekend nights with friends involved drinking or using drugs. Friends-based strategies were used on 29% of nights. Across models, being with one or more intoxicated friends was associated with friends-based strategy use and an unwanted sexual experience, but only at the situation level. Parents, educators, and policy makers can encourage college women to draw on their social networks to enhance safety. Interventions could incorporate more universal strategies for responding to risk in social contexts

The Solar Neighborhood. XXXIV. A Search for Planets Orbiting Nearby M Dwarfs using Astrometry

Astrometric measurements are presented for seven nearby stars with previously detected planets: six M dwarfs (GJ 317, GJ 667C, GJ 581, GJ 849, GJ 876, and GJ 1214) and one K dwarf (BD $-$10 3166). Measurements are also presented for six additional nearby M dwarfs without known planets, but which are more favorable to astrometric detections of low mass companions, as well as three binary systems for which we provide astrometric orbit solutions. Observations have baselines of three to thirteen years, and were made as part of the RECONS long-term astrometry and photometry program at the CTIO/SMARTS 0.9m telescope. We provide trigonometric parallaxes and proper motions for all 16 systems, and perform an extensive analysis of the astrometric residuals to determine the minimum detectable companion mass for the 12 M dwarfs not having close stellar secondaries. For the six M dwarfs with known planets, we are not sensitive to planets, but can rule out the presence of all but the least massive brown dwarfs at periods of 2 - 12 years. For the six more astrometrically favorable M dwarfs, we conclude that none have brown dwarf companions, and are sensitive to companions with masses as low as 1 $M_{Jup}$ for periods longer than two years. In particular, we conclude that Proxima Centauri has no Jovian companions at orbital periods of 2 - 12 years. These results complement previously published M dwarf planet occurrence rates by providing astrometrically determined upper mass limits on potential super-Jupiter companions at orbits of two years and longer. As part of a continuing survey, these results are consistent with the paucity of super-Jupiter and brown dwarf companions we find among the over 250 red dwarfs within 25 pc observed longer than five years in our astrometric program.Comment: 18 pages, 5 figures, 4 tables, accepted for publication in A

Selenium hyperaccumulation offers protection from cell disruptor herbivores

<p>Abstract</p> <p>Background</p> <p>Hyperaccumulation, the rare capacity of certain plant species to accumulate toxic trace elements to levels several orders of magnitude higher than other species growing on the same site, is thought to be an elemental defense mechanism against herbivores and pathogens. Previous research has shown that selenium (Se) hyperaccumulation protects plants from a variety of herbivores and pathogens. Selenium hyperaccumulating plants sequester Se in discrete locations in the leaf periphery, making them potentially more susceptible to some herbivore feeding modes than others. In this study we investigate the protective function of Se in the Se hyperaccumulators <it>Stanleya pinnata </it>and <it>Astragalus bisulcatus </it>against two cell disrupting herbivores, the western flower thrips (<it>Frankliniella occidentalis</it>) and the two-spotted spider mite (<it>Tetranychus urticae</it>).</p> <p>Results</p> <p><it>Astragalus bisulcatus </it>and <it>S. pinnata </it>with high Se concentrations (greater than 650 mg Se kg^-1) were less subject to thrips herbivory than plants with low Se levels (less than 150 mg Se kg^-1). Furthermore, in plants containing elevated Se levels, leaves with higher concentrations of Se suffered less herbivory than leaves with less Se. Spider mites also preferred to feed on low-Se <it>A. bisulcatus </it>and <it>S. pinnata </it>plants rather than high-Se plants. Spider mite populations on <it>A. bisulcatus </it>decreased after plants were given a higher concentration of Se. Interestingly, spider mites could colonize <it>A. bisulcatus </it>plants containing up to 200 mg Se kg^-1dry weight, concentrations which are toxic to many other herbivores. Selenium distribution and speciation studies using micro-focused X-ray fluorescence (μXRF) mapping and Se K-edge X-ray absorption spectroscopy revealed that the spider mites accumulated primarily methylselenocysteine, the relatively non-toxic form of Se that is also the predominant form of Se in hyperaccumulators.</p> <p>Conclusions</p> <p>This is the first reported study investigating the protective effect of hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.</p

The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer

Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A cohort of 150 patients with stage I‐III CRC were utilised to assess tumour cell expression of MCT‐1, MCT‐2, LDH‐1 and LDH‐5 by immunohistochemistry. Expression levels were dichotomised and associations with tumour factors, the tumour microenvironment and survival analysed. Nuclear LDH‐5 associates with poor prognosis (HR 1.68 95% CI 0.99–2.84, p = 0.050) and trends toward increased tumour stroma percentage (TSP, p = 0.125). Cytoplasmic MCT‐2 also trends toward increased TSP (p = 0.081). When combined into a single score; nuclear LDH‐5 + TSP significantly associated with decreased survival independent of stage (HR 2.61 95% CI 1.27–5.35, p = 0.009), increased tumour budding (p = 0.002) and decreased stromal T‐lymphocytes (p = 0.014). Similarly, cytoplasmic MCT‐2 + TSP significantly associated with decreased survival (HR 2.32 95% CI 1.31–4.11, p = 0.003), decreased necrosis (p = 0.039), and increased tumour budding (p = 0.004). The present study reports that the combination of TSP and nuclear LDH‐5 was significantly associated with survival, increased tumour budding, and decreased stromal T‐lymphocytes. This supports the hypothesis that increased stromal invasion promotes tumour progression via modulation of tumour metabolism. Moreover, MCT‐2 and LDH‐5 may provide promising therapeutic targets for patients with stromal‐rich CRC

Gemini Planet Imager Observational Calibrations VI: Photometric and Spectroscopic Calibration for the Integral Field Spectrograph

The Gemini Planet Imager (GPI) is a new facility instrument for the Gemini Observatory designed to provide direct detection and characterization of planets and debris disks around stars in the solar neighborhood. In addition to its extreme adaptive optics and corona graphic systems which give access to high angular resolution and high-contrast imaging capabilities, GPI contains an integral field spectrograph providing low resolution spectroscopy across five bands between 0.95 and 2.5 $\mu$m. This paper describes the sequence of processing steps required for the spectro-photometric calibration of GPI science data, and the necessary calibration files. Based on calibration observations of the white dwarf HD 8049B we estimate that the systematic error in spectra extracted from GPI observations is less than 5%. The flux ratio of the occulted star and fiducial satellite spots within coronagraphic GPI observations, required to estimate the magnitude difference between a target and any resolved companions, was measured in the $H$-band to be $\Delta m = 9.23\pm0.06$ in laboratory measurements and $\Delta m = 9.39\pm 0.11$ using on-sky observations. Laboratory measurements for the $Y$, $J$, $K1$ and $K2$ filters are also presented. The total throughput of GPI, Gemini South and the atmosphere of the Earth was also measured in each photometric passband, with a typical throughput in $H$-band of 18% in the non-coronagraphic mode, with some variation observed over the six-month period for which observations were available. We also report ongoing development and improvement of the data cube extraction algorithm.Comment: 15 pages, 6 figures. Proceedings of the SPIE, 9147-30