Improved Dynamical Constraints on the Masses of the Central Black Holes in Nearby Low-mass Early-type Galactic Nuclei And the First Black Hole Determination for NGC 205

We improve the dynamical black hole (BH) mass estimates in three nearby low-mass early-type galaxies--NGC 205, NGC 5102, and NGC 5206. We use new \hst/STIS spectroscopy to fit the star formation histories of the nuclei in these galaxies, and use these measurements to create local color--mass-to-light ratio (\ml) relations. We then create new mass models from \hst~imaging and combined with adaptive optics kinematics, we use Jeans dynamical models to constrain their BH masses. The masses of the central BHs in NGC 5102 and NGC 5206 are both below one million solar masses and are consistent with our previous estimates, $9.12_{-1.53}^{+1.84}\times10^5$\Msun~and $6.31_{-2.74}^{+1.06}\times10^5$\Msun~(3$\sigma$ errors), respectively. However, for NGC 205, the improved models suggest the presence of a BH for the first time, with a best-fit mass of $6.8_{-6.7}^{+95.6}\times10^3$\Msun~(3$\sigma$ errors). This is the least massive central BH mass in a galaxy detected using any method. We discuss the possible systematic errors of this measurement in detail. Using this BH mass, the existing upper limits of both X-ray, and radio emissions in the nucleus of NGC 205 suggest an accretion rate $\lesssim$$10^{-5}$ of the Eddington rate. We also discuss the color--\mleff~relations in our nuclei and find that the slopes of these vary significantly between nuclei. Nuclei with significant young stellar populations have steeper color--\mleff~relations than some previously published galaxy color--\mleff~relations.Comment: 31 pages, 19 figures, 6 tables, Accepted to Ap

Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2

<p>Abstract</p> <p>Background</p> <p>The gene <it>CHEK2 </it>encodes a checkpoint kinase playing a key role in the DNA damage pathway. Though <it>CHEK2 </it>has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. The detection of differential allelic expression (DAE) represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. We aimed to assess whether <it>CHEK2 </it>was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation in <it>BRCA1</it> or <it>BRCA2</it> had been identified.</p> <p>Methods</p> <p>We implemented an assay based on high-resolution melting (HRM) curve analysis and developed an analysis tool for DAE assessment.</p> <p>Results</p> <p>We observed allelic expression imbalance in 4 of the 41 LCLs examined. All four were carriers of the truncating mutation 1100delC. We confirmed previous findings that this mutation induces non-sense mediated mRNA decay. In our series, we ruled out the possibility of a functional sequence variant located in the promoter region or in a regulatory element of <it>CHEK2 </it>that would lead to DAE in the transcriptional regulatory milieu of freely proliferating LCLs.</p> <p>Conclusions</p> <p>Our results support that HRM is a sensitive and accurate method for DAE assessment. This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms.</p

PMm2: large photomultipliers and innovative electronics for the next-generation neutrino experiments

The next generation of proton decay and neutrino experiments, the post-SuperKamiokande detectors as those that will take place in megaton size water tanks, will require very large surfaces of photodetection and a large volume of data. Even with large hemispherical photomultiplier tubes, the expected number of channels should reach hundreds of thousands. A funded R&D program to implement a solution is presented here. The very large surface of photodetection is segmented in macro pixels made of 16 hemispherical (12 inches) photomultiplier tubes connected to an autonomous front-end which works on a triggerless data acquisition mode. The expected data transmission rate is 5 Mb/s per cable, which can be achieved with existing techniques. This architecture allows to reduce considerably the cost and facilitate the industrialization. This document presents the simulations and measurements which define the requirements for the photomultipliers and the electronics. A proto-type of front-end electronics was successfully tested with 16 photomultiplier tubes supplied by a single high voltage, validating the built-in gain adjustment and the calibration principle. The first tests and calculations on the photomultiplier glass led to the study of a new package optimized for a 10 bar pressure in order to sustain the high underwater pressure.Comment: 1 pdf file, 4 pages, 4 figures, NDIP08, submitted to Nucl. Instr. and Meth. Phys. Res.

Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men.

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.93, 95% CI = 0.76-1.13, P = 0.46) or aggressive (aggregate OR = 1.14, 95% CI = 0.92-1.41, P = 0.22) prostate cancer risk. CHIP was weakly associated with genetic risk of overall prostate cancer, measured using a polygenic risk score (OR = 1.05 per unit increase, 95% CI = 1.01-1.10, P = 0.01). CHIP was not significantly associated with carrying pathogenic/likely pathogenic/deleterious variants in DNA repair genes, which have previously been found to be associated with aggressive prostate cancer. While findings from this study suggest that CHIP is likely not a risk factor for prostate cancer, it will be important to investigate other types of CH in association with prostate cancer risk

Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy

Introduction: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, postsurgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous lymph node transplantation has the potential to reduce or prevent edema development. In this report, we examine the potential of lymphangiogenic therapy to restore lymphatic function and reduce postsurgical lymphedema. Methods: Lymphangiogenic growth factors (vascular endothelial growth factor C (VEGF-C)) and angiopoietin-2 (ANG-2) were loaded into a gel-based drug delivery system (HAMC; a blend of hyaluronan and methylcellulose). Drug release rates and lymphangiogenic signaling in target endothelial cells were assessed in vitro and vascular permeability biocompatibility tests were examined in vivo. Following, the removal of a single popliteal lymph node, HAMC with the growth factors was injected into the excision site. Six weeks later, lymphatic functionality was assessed by injecting 125Iodine radiolabeled bovine serum albumin (125I-BSA) into prenodal vessels and measuring its recovery in plasma. Circumferential leg measurements were plotted over time and areas under the curves used to quantify edema formation. Results: The growth factors were released over a two-week period in vitro by diffusion from HAMC, with 50% being released in the first 24 hr. The system induced lymphangiogenic signaling in target endothelial cells, while inducing only a minimal inflammatory response in sheep. Removal of the node significantly reduced lymphatic functionality (nodectomy 1.9 ± 0.9, HAMC alone 1.7 ± 0.8) compared with intact groups (3.2 ± 0.7). In contrast, there was no significant difference between the growth factor treatment group (2.3 ± 0.73) and the intact group indicating improved function with the molecular factors. An increase in the number of regenerated lymphatic vessels at treatment sites was observed with fluoroscopy. Groups receiving HAMC plus growth factors displayed significantly reduced edema (107.4 ± 51.3) compared with nontreated groups (nodectomy 219.8 ± 118.7 and HAMC alone 162.6 ± 141). Conclusions: Growth factor therapy has the potential to increase lymphatic function and reduce edema magnitude in an animal model of lymphedema. The application of this concept to lymphedema patients warrants further examination