Dry law and homicides: evidence from the São Paulo metropolitan area

Over the last 15 years, several Latin American cities have adopted dry laws, which restrain the sale of alcohol in bars and restaurants during specific hours of the week. Bogotá, in 1991, was the first. Several more have followed suit, or are likely to do so in the near future. Policy makers and the general press have argued that these measures reduce crime. In this paper, we use a particular feature of the adoption of laws in the São Paulo Metropolitan Area (SPMA) to estimate the effect of dry laws on the ultimate form of violent crime: murder. Between March 2001 and August 2004, 16 out of the 39 municipalities of the SPMA have adopted, at different dates, dry laws. By comparing the dynamics of homicide between adopting and non-adopting cities, we estimate that dry laws reduce homicides by at least 10%, with an even higher effect in high crime cities. Results are robust to inclusion of a large set of controls, to propensity score matching, to outliers, and to correction possible spillover effects from adopting to non-adopting cities.Dry Law, Alcohol, Crime, Difference-in-Difference

Results from the Supernova Photometric Classification Challenge

We report results from the Supernova Photometric Classification Challenge (SNPCC), a publicly released mix of simulated supernovae (SNe), with types (Ia, Ibc, and II) selected in proportion to their expected rate. The simulation was realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point-spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). A spectroscopically confirmed subset was provided for training. We challenged scientists to run their classification algorithms and report a type and photo-z for each SN. Participants from 10 groups contributed 13 entries for the sample that included a host-galaxy photo-z for each SN, and 9 entries for the sample that had no redshift information. Several different classification strategies resulted in similar performance, and for all entries the performance was significantly better for the training subset than for the unconfirmed sample. For the spectroscopically unconfirmed subset, the entry with the highest average figure of merit for classifying SNe~Ia has an efficiency of 0.96 and an SN~Ia purity of 0.79. As a public resource for the future development of photometric SN classification and photo-z estimators, we have released updated simulations with improvements based on our experience from the SNPCC, added samples corresponding to the Large Synoptic Survey Telescope (LSST) and the SDSS, and provided the answer keys so that developers can evaluate their own analysis.Comment: accepted by PAS

Stringent Limits on the Polarized Submillimeter Emission from Protoplanetary Disks

We present arcsecond-resolution Submillimeter Array (SMA) polarimetric observations of the 880 um continuum emission from the protoplanetary disks around two nearby stars, HD 163296 and TW Hydrae. Although previous observations and theoretical work have suggested that a 2-3% polarization fraction should be common for the millimeter continuum emission from such disks, we detect no polarized continuum emission above a 3-sigma upper limit of 7 mJy in each arcsecond-scale beam, or <1% in integrated continuum emission. We compare the SMA upper limits with the predictions from the exploratory Cho & Lazarian (2007) model of polarized emission from T Tauri disks threaded by toroidal magnetic fields, and rule out their fiducial model at the ~10-sigma level. We explore some potential causes for this discrepancy, focusing on model parameters that describe the shape, magnetic field alignment, and size distribution of grains in the disk. We also investigate related effects like the magnetic field strength and geometry, scattering off of large grains, and the efficiency of grain alignment, including recent advances in grain alignment theory, which are not considered in the fiducial model. We discuss the impact each parameter would have on the data and determine that the suppression of polarized emission plausibly arises from rounding of large grains, reduced efficiency of grain alignment with the magnetic field, and/or some degree of magnetic field tangling (perhaps due to turbulence). A poloidal magnetic field geometry could also reduce the polarization signal, particularly for a face-on viewing geometry like the TW Hya disk. The data provided here offer the most stringent limits to date on the polarized millimeter-wavelength emission from disks around young stars.Comment: 15 pages, 6 figures, accepted for publication in Ap

Discovery of a small molecule ligand of FRS2 that inhibits invasion and tumor growth

Purpose: Aberrant activation of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases drives oncogenic signaling through its proximal adaptor protein FRS2. Precise disruption of this disease-causing signal transmission in metastatic cancers could stall tumor growth and progression. The purpose of this study was to identify a small molecule ligand of FRS2 to interrupt oncogenic signal transmission from activated FGFRs. Methods: We used pharmacophore-based computational screening to identify potential small molecule ligands of the PTB domain of FRS2, which couples FRS2 to FGFRs. We confirmed PTB domain binding of molecules identified with biophysical binding assays and validated compound activity in cell-based functional assays in vitro and in an ovarian cancer model in vivo. We used thermal proteome profiling to identify potential off-targets of the lead compound. Results: We describe a small molecule ligand of the PTB domain of FRS2 that prevents FRS2 activation and interrupts FGFR signaling. This PTB-domain ligand displays on-target activity in cells and stalls FGFR-dependent matrix invasion in various cancer models. The small molecule ligand is detectable in the serum of mice at the effective concentration for prolonged time and reduces growth of the ovarian cancer model in vivo. Using thermal proteome profiling, we furthermore identified potential off-targets of the lead compound that will guide further compound refinement and drug development. Conclusions: Our results illustrate a phenotype-guided drug discovery strategy that identified a novel mechanism to repress FGFR-driven invasiveness and growth in human cancers. The here identified bioactive leads targeting FGF signaling and cell dissemination provide a novel structural basis for further development as a tumor agnostic strategy to repress FGFR- and FRS2-driven tumors. Keywords: Bioactive small molecule compound; Cell invasion; FGFR; FRS2; Protein–protein interaction interference; Thermal proteome profilin

Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors

Trost E, Al-Dilaimi A, Papavasiliou P, et al. Comparative analysis of two complete Corynebacterium ulcerans genomes and detection of candidate virulence factors. BMC Genomics. 2011;12(1): 383.ABSTRACT: Corynebacterium ulcerans has been detected as a commensal in domestic and wild animals that may serve as reservoirs for zoonotic infections. During the last decade, the frequency and severity of human infections associated with C. ulcerans appear to be increasing in various countries. As the knowledge of genes contributing to the virulence of this bacterium was very limited, the complete genome sequences of two C. ulcerans strains detected in the metropolitan area of Rio de Janeiro were determined and characterized by comparative genomics: C. ulcerans 809 was initially isolated from an elderly woman with fatal pulmonary infection and C. ulcerans BR-AD22 was recovered from a nasal sample of an asymptomatic dog. The circular chromosome of C. ulcerans 809 has a total size of 2,502,095 bp and encodes 2,182 predicted proteins, whereas the genome of C. ulcerans BR-AD22 is 104,279 bp larger and comprises 2,338 protein-coding regions. The minor difference in size of the two genomes is mainly caused by additional prophage-like elements in the C. ulcerans BR-AD22 chromosome. Both genomes show a highly similar order of orthologous coding regions; and both strains share a common set of 2,076 genes, demonstrating their very close relationship. A screening for prominent virulence factors revealed the presence of phospholipase D (Pld), neuraminidase H (NanH), endoglycosidase E (EndoE), and subunits of adhesive pili of the SpaDEF type that are encoded in both C. ulcerans genomes. The rbp gene coding for a putative ribosome-binding protein with striking structural similarity to Shiga-like toxins was additionally detected in the genome of the human isolate C. ulcerans 809. The molecular data deduced from the complete genome sequences provides considerable knowledge of virulence factors in C. ulcerans that is increasingly recognized as an emerging pathogen. This bacterium is apparently equipped with a broad and varying set of virulence factors, including a novel type of a ribosome-binding protein. Whether the respective protein contributes to the severity of human infections (and a fatal outcome) remains to be elucidated by genetic experiments with defined bacterial mutants and host model systems

Weak Gravitational Lensing by Large-Scale Structure

Weak gravitational lensing provides a unique method to map directly the distribution of dark matter in the universe and to measure cosmological parameters. This cosmic-shear technique is based on the measurement of the weak distortions that lensing induces in the shape of background galaxies as photons travel through large-scale structures. This technique is now widely used to measure the mass distribution of galaxy clusters and has recently been detected in random regions of the sky. In this review, we present the theory and observational status of cosmic shear. We describe the principles of weak lensing and the predictions for the shear statistics in favored cosmological models. Next, we review the current measurements of cosmic shear and show how they constrain cosmological parameters. We then describe the prospects offered by upcoming and future cosmic-shear surveys as well as the technical challenges that have to be met for the promises of cosmic shear to be fully realized.Comment: 25 latex pages, including 10 figures and 2 tables. to appear in Annual Reviews of Astronomy and Astrophysics 2003, vol. 4

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

Childhood brain tumors: A review of strategies to translate CNS drug delivery to clinical trials

Brain tumors account for over 20% of childhood cancers and are the biggest cancer killer in children and young adults. Several initiatives over the past 40 years have tried to identify more effective drug treatments, but with very limited success. This is largely due to the bloodâ brain barrier, which restricts the entry of many drugs into the brain. In this review, we describe the main techniques that are being developed to enhance brain tumor drug delivery and explore the preclinical brain tumor models that are essential for translational development of these techniques. We also identify existing approved drugs that, if coupled with an efficient delivery method, could have potential as brain tumor treatments. Bringing this information together is part of a funded initiative to highlight drug delivery as a research strategy to overcome the current challenges for children diagnosed with brain tumors

Interpolation in variable exponent spaces

In this paper we study both real and complex interpolation in the recently introduced scales of variable exponent Besov and Triebel–Lizorkin spaces. We also take advantage of some interpolation results to study a trace property and some pseudodifferential operators acting in the variable index Besov scale