Radical Surgery in the Treatment of Localized Carcinoma of the Prostate

New methods of early detection combined with recent advances in surgical techniques have resulted in more patients undergoing radical surgery for treatment of localized carcinoma of the prostate. Over 350 radical prostatectomies have been performed by our group since January 1987. We review the role of radical prostatectomy in the treatment of prostate cancer and our experience with 100 patients undergoing radical retropubic prostatectomy since the advent of nerve-sparing techniques to preserve potency

VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions

Background: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age-and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). Methods: Chat-ChR2-EYFP (VAChTHyp) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1G93A), and Chat-IRES-Cre and tdTomato transgenic mice were used in this study. NMJs, muscle fibers, and a-motor neurons\u27 somata and their axons were examined using a light microscope. Transcripts for select genes in muscles and spinal cords were assessed using real-time quantitative PCR. Motor function tests were carried out using an inverted wire mesh and a rotarod. Electrophysiological recordings were collected to examine miniature endplate potentials (MEPP) in muscles. Results: We show that VAChT is elevated in the spinal cord and at NMJs of VAChTHyp mice. We also show that the amplitude of MEPPs is significantly higher in VAChTHyp muscles, indicating that more ACh is loaded into synaptic vesicles and released into the synaptic cleft at NMJs of VAChTHyp mice compared to control mice. While the development of NMJs was not affected in VAChTHyp mice, NMJs prematurely acquired age-related structural alterations in adult VAChTHyp mice. These structural changes at NMJs were accompanied by motor deficits in VAChTHyp mice. However, cellular features of muscle fibers and levels of molecules with critical functions at the NMJ and in muscle fibers were largely unchanged in VAChTHyp mice. In the SOD1G93A mouse model for ALS, increasing synaptic ACh accelerated degeneration of NMJs caused motor deficits and resulted in premature death specifically in male mice. Conclusions: The data presented in this manuscript demonstrate that increasing levels of ACh at the synaptic cleft promote degeneration of adult NMJs, contributing to age-and disease-related motor deficits. We thus propose that maintaining normal cholinergic signaling in muscles will slow degeneration of NMJs and attenuate loss of motor function caused by aging and neuromuscular diseases

TOI-150: A transiting hot Jupiter in the TESS southern CVZ

We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J}$,$R_{p}=1.38\pm0.04\ R_{J}$) orbiting a middle-aged star ($\log g=4.152^{+0.030}_{-0.043}$) in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone ($\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ

Kepler-730: A hot Jupiter system with a close-in, transiting, Earth-sized planet

Kepler-730 is a planetary system hosting a statistically validated hot Jupiter in a 6.49-day orbit and an additional transiting candidate in a 2.85-day orbit. We use spectroscopic radial velocities from the APOGEE-2N instrument, Robo-AO contrast curves, and Gaia distance estimates to statistically validate the planetary nature of the additional Earth-sized candidate. We perform astrophysical false positive probability calculations for the candidate using the available Kepler data and bolster the statistical validation by using radial velocity data to exclude a family of possible binary star solutions. Using a radius estimate for the primary star derived from stellar models, we compute radii of $1.100^{+0.047}_{-0.050}\ R_{Jup}$ and $0.140\pm0.012\ R_{Jup}$ ($1.57\pm0.13\ R_{\oplus}$) for Kepler-730b and Kepler-730c, respectively. Kepler-730 is only the second compact system hosting a hot Jupiter with an inner, transiting planet.Comment: 13 pages, 2 figures, 3 tables, published in ApJ

Characterization of low-mass companions to Kepler\textit{Kepler} objects of interest observed with APOGEE-N

We report the characterization of 28 low-mass ($0.02\mathrm{~M_\odot}\le\mathrm{~M_{2}}\le0.25\mathrm{~M_\odot}$) companions to $\textit{Kepler}$ objects of interest (KOIs), eight of which were previously designated confirmed planets. These objects were detected as transiting companions to Sun-like stars (G and F dwarfs) by the $\textit{Kepler}$ mission and are confirmed as single-lined spectroscopic binaries in the current work using the northern multiplexed Apache Point Observatory Galactic Evolution Experiment near-infrared spectrograph (APOGEE-N) as part of the third and fourth Sloan Digital Sky Surveys. We have observed hundreds of KOIs using APOGEE-N and collected a total of 43,175 spectra with a median of 19 visits and a median baseline of $\sim1.9$ years per target. We jointly model the $\textit{Kepler}$ photometry and APOGEE-N radial velocities to derive fundamental parameters for this subset of 28 transiting companions. The radii for most of these low-mass companions are over-inflated (by $\sim10\%$) when compared to theoretical models. Tidally locked M dwarfs on short period orbits show the largest amount of inflation, but inflation is also evident for companions that are well separated from the host star. We demonstrate that APOGEE-N data provides reliable radial velocities when compared to precise high-resolution spectrographs that enable detailed characterization of individual systems and the inference of orbital elements for faint ($H>12$) KOIs. The data from the entire APOGEE-KOI program is public and presents an opportunity to characterize an extensive subset of the binary population observed by $\textit{Kepler}$.Comment: 98 pages (include 56 for the figure sets), 10 tables, 7 figures, 2 figure sets, accepted for publication in ApJ

Kepler-503b: An Object at the Hydrogen Burning Mass Limit Orbiting a Subgiant Star

Using spectroscopic radial velocities with the APOGEE instrument and Gaia distance estimates, we demonstrate that Kepler-503b, currently considered a validated Kepler planet, is in fact a brown-dwarf/low-mass star in a nearly circular 7.2-day orbit around a subgiant star. Using a mass estimate for the primary star derived from stellar models, we derive a companion mass and radius of $0.075\pm0.003 \ M_{\odot}$ ($78.6\pm3.1 \ M_{Jup}$) and $0.099^{+0.006}_{-0.004}\ R_{\odot}$ ($0.96^{+0.06}_{-0.04}\ R_{Jup}$), respectively. Assuming the system is coeval, the evolutionary state of the primary indicates the age is $\sim6.7$ Gyr. Kepler-503b sits right at the hydrogen burning mass limit, straddling the boundary between brown dwarfs and very low-mass stars. More precise radial velocities and secondary eclipse spectroscopy with James Webb Space Telescope will provide improved measurements of the physical parameters and age of this important system to better constrain and understand the physics of these objects and their spectra. This system emphasizes the value of radial velocity observations to distinguish a genuine planet from astrophysical false positives, and is the first result from the SDSS-IV monitoring of Kepler planet candidates with the multi-object APOGEE instrument.Comment: Accepted for publication in ApJL, 12 pages, 3 figures, 2 table

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

The When and Why: Student Entrepreneurial Aspirations

Although connections between university enterprise courses and entrepreneurial activity have been examined, less work has investigated the intended timing of future entrepreneurial activities. Using data from a survey of U.K. business students, it is found that those intending to enter entrepreneurship right away place less emphasis on avoiding stress and responsibility, seeing themselves as natural leaders. They were also more confident of succeeding, but not because of superior knowledge. A greater emphasis on entrepreneurial activities in all institutional environments, including the corporate, may help balance the need to harness enthusiasm while it lasts with the need to acquire relevant experience

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development. Statement of significance PDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors