Cross-correlation between the soft X-ray background and SZ Sky

While both X-ray emission and Sunyaev-Zel'dovich (SZ) temperature fluctuations are generated by the warm-hot gas in dark matter halos, the two observables have different dependence on the underlying physical properties, including the gas distribution. A cross-correlation between the soft X-ray background (SXRB) and the SZ sky may allow an additional probe on the distribution of warm-hot gas at intermediate angular scales and redshifts complementing studies involving clustering within SXRB and SZ separately. Using a halo approach, we investigate this cross-correlation analytically. The two contributions are correlated mildly with a correlation coefficient of $\sim0.3$, and this relatively low correlation presents a significant challenge for its detection. The correlation, at small angular scales, is affected by the presence of radiative cooling or preheating and provides a probe on the thermal history of the hot gas in dark halos. While the correlation remains undetectable with CMB data from the WMAP satellite and X-ray background data from existing catalogs, upcoming observations with CMB missions such as Planck, for the SZ side, and an improved X-ray map of the large scale structure, such as the one planned with DUET mission, may provide a first opportunity for a reliable detection of this cross-correlation.Comment: 8 pages, 6 figures, accepted for publication in A&

Prolyl Isomerase Pin1 is Highly Expressed in Her2-Positive Breast Cancer and Regulates erbB2 Protein Stability

Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed postphosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods: Immunohistochemistry for Her2 and Pin1 were performed on two hundred twentythree human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results: Sixty-four samples (28.7%) stained positive for Her2 (IHC 3+), and 54% (122/223) of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5%) were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL. Conclusion: Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells

Cetuximab as Second-Line Therapy in Patients with Metastatic Esophageal Adenocarcinoma: A Phase II Southwest Oncology Group Study (S0415)

IntroductionEsophageal adenocarcinomas commonly express the epidermal growth factor receptor. This trial assessed the 6-month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as second-line therapy.MethodsThis was a multicenter, open-label phase II study of single-agent cetuximab for metastatic esophageal adenocarcinoma patients who failed one prior chemotherapy regimen. Adequate organ function and Zubrod performance status of 0 to 2 were required. Patients received cetuximab 400 mg/m2 intravenously (IV) on week 1 and 250 mg/m2 IV weekly thereafter. The primary objective was to determine 6-month overall survival. Secondary end points included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies.ResultsSixty-three patients were registered, with eight ineligible or never treated. Fifty-five eligible patients (49 men, 6 women; median age = 61.2 years [range, 30.7–88.5]) were enrolled. Twenty patients survived more than 6 months for a 6-month overall survival rate of 36% (95% confidence interval [CI]: 24–50%). The median overall survival was 4.0 months (95% CI: 3.2–5.9). Median progression-free survival was 1.8 months (95% CI: 1.7–1.9). One partial response and two unconfirmed partial responses were observed. Two patients experienced grade 4 fatigue. There was one treatment-related death due to pneumonitis. Germline polymorphisms of epidermal growth factor receptor, epidermal growth factor, interleukin (IL)-8, cyclooxygenase (COX)-2, vascular epidermal growth factor receptor (VEGF), CCND1, neuropilin 1 (NRP1), and K-ras mutational status were not associated with response or survival.ConclusionsThe 6-month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer

Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself

Probing O-H Bonding Through Proton Detected 1H-17O Double Resonance Solid-State NMR Spectroscopy

The ubiquity of oxygen in organic, inorganic, and biological systems has stimulated the application and development of 17O solid-state NMR spectroscopy as a probe of molecular structure and dynamics. Unfortunately, 17O solid-state NMR experiments are often hindered by the combination of broad NMR signals and low sensitivity. Here, it is demonstrated that fast MAS and proton detection with the D-RINEPT pulse sequence can be generally applied to enhance the sensitivity and resolution of 17O solid-state NMR experiments. Complete 2D 17O→1H D-RINEPT correlation NMR spectra were typically obtained in fewer than 10 hours from less than 10 milligrams of material, with low to moderate 17O enrichment (less than 20%). 2D 1H-17O correlation solid-state NMR spectra allow overlapping oxygen sites to be resolved on the basis of proton chemical shifts or by varying the mixing time used for 1H-17O magnetization transfer. In addition, J-resolved or separated local field (SLF) blocks can be incorporated into the D-RINEPT pulse sequence to allow direct measurement of one-bond 1H-17O scalar coupling constants (1JOH) or 1H-17O dipolar couplings (DOH), respectively; the latter of which can be used to infer 1H-17O bond lengths. 1JOH and DOH calculated from planewave density functional theory (DFT) show very good agreement with experimental values. Therefore, the 2D 1H-17O correlation experiments, 1H-17O scalar and dipolar couplings, and planewave DFT calculations provide a method to precisely determine proton positions relative to oxygen atoms. This capability opens new opportunities to probe interactions between oxygen and hydrogen in a variety of chemical systems

Generalized McKay quivers of rank three

For each finite subgroup G of SL(n, C), we introduce the generalized Cartan matrix C_{G} in view of McKay correspondence from the fusion rule of its natural representation. Using group theory, we show that the generalized Cartan matrices have similar favorable properties such as positive semi-definiteness as in the classical case of affine Cartan matrices (the case of SL(2,C)). The complete McKay quivers for SL(3,C) are explicitly described and classified based on representation theory

Constraining Intra-cluster Gas Models with AMiBA13

Clusters of galaxies have been used extensively to determine cosmological parameters. A major difficulty in making best use of Sunyaev-Zel'dovich (SZ) and X-ray observations of clusters for cosmology is that using X-ray observations it is difficult to measure the temperature distribution and therefore determine the density distribution in individual clusters of galaxies out to the virial radius. Observations with the new generation of SZ instruments are a promising alternative approach. We use clusters of galaxies drawn from high-resolution adaptive mesh refinement (AMR) cosmological simulations to study how well we should be able to constrain the large-scale distribution of the intra-cluster gas (ICG) in individual massive relaxed clusters using AMiBA in its configuration with 13 1.2-m diameter dishes (AMiBA13) along with X-ray observations. We show that non-isothermal beta models provide a good description of the ICG in our simulated relaxed clusters. We use simulated X-ray observations to estimate the quality of constraints on the distribution of gas density, and simulated SZ visibilities (AMiBA13 observations) for constraints on the large-scale temperature distribution of the ICG. We find that AMiBA13 visibilities should constrain the scale radius of the temperature distribution to about 50% accuracy. We conclude that the upgraded AMiBA, AMiBA13, should be a powerful instrument to constrain the large-scale distribution of the ICG.Comment: Accepted for publication in The Astrophysical Journal, 12 pages, 9 figure

Combining Semi-analytic Models with Simulations of Galaxy Clusters: the Need for Heating from Active Galactic Nuclei

We present hydrodynamical N-body simulations of clusters of galaxies with feedback taken from semi-analytic models of galaxy formation. The advantage of this technique is that the source of feedback in our simulations is a population of galaxies that closely resembles that found in the real universe. We demonstrate that, to achieve the high entropy levels found in clusters, active galactic nuclei must inject a large fraction of their energy into the intergalactic/intracluster media throughout the growth period of the central black hole. These simulations reinforce the argument of Bower et al., who arrived at the same conclusion on the basis of purely semi-analytic reasoning.Comment: 25 pages and 10 colour figures. Accepted by Ap