Political Repression in the Developing World: Does the Military Play a Role?

Also PCMA Working Paper #25.http://deepblue.lib.umich.edu/bitstream/2027.42/51201/1/434.pd

Identification of Listeria monocytogenes Determinants Required for Biofilm Formation

Listeria monocytogenes is a Gram-positive, food-borne pathogen of humans and animals. L. monocytogenes is considered to be a potential public health risk by the U.S. Food and Drug Administration (FDA), as this bacterium can easily contaminate ready-to-eat (RTE) foods and cause an invasive, life-threatening disease (listeriosis). Bacteria can adhere and grow on multiple surfaces and persist within biofilms in food processing plants, providing resistance to sanitizers and other antimicrobial agents. While whole genome sequencing has led to the identification of biofilm synthesis gene clusters in many bacterial species, bioinformatics has not identified the biofilm synthesis genes within the L. monocytogenes genome. To identify genes necessary for L. monocytogenes biofilm formation, we performed a transposon mutagenesis library screen using a recently constructed Himar1 mariner transposon. Approximately 10,000 transposon mutants within L. monocytogenes strain 10403S were screened for biofilm formation in 96-well polyvinyl chloride (PVC) microtiter plates with 70 Himar1 insertion mutants identified that produced significantly less biofilms. DNA sequencing of the transposon insertion sites within the isolated mutants revealed transposon insertions within 38 distinct genetic loci. The identification of mutants bearing insertions within several flagellar motility genes previously known to be required for the initial stages of biofilm formation validated the ability of the mutagenesis screen to identify L. monocytogenes biofilm-defective mutants. Two newly identified genetic loci, dltABCD and phoPR, were selected for deletion analysis and both ΔdltABCD and ΔphoPR bacterial strains displayed biofilm formation defects in the PVC microtiter plate assay, confirming these loci contribute to biofilm formation by L. monocytogenes

Initial trail results of a magnetic biosensor for the rapid detection of Porcine Reproductive and Respiratory Virus (PRRSV) infection

© 2019 The resonant coil magnetometer quantifies paramagnetic particles (PMPs) and has been used to develop magneto-immunoassays in a range of formats. The advantage of magneto-immunoassays is that they are relatively inexpensive, portable, easy to perform and give results in under 5 min. Porcine Reproductive and Respiratory Virus (PRRSV) is an infection of domesticated pigs producing large economic losses in the swine industry current diagnosis is performed using commercially available ELISA kits. Here we describe the development of a competitive magneto-immunoassay (MIA) and pilot study with porcine serum samples. The data show that this technology has the potential for use as a rapid and portable in field system for the detection of antibodies in porcine serum to PRRSV. A range of assay parameters and magnetometer settings were optimised, including the concentration of antibody conjugated PMPs used in the assay and movement of an external magnet to pull particles to a sensor surface. PRRSV positive control serum demonstrated competition with antibody conjugated PMPs with a dose dependent relationship. The magneto-immunoassay developed showed good agreement with the PRRS IDEXX X3 ELISA. The PRRSV magneto-immunoassay demonstrated a sensitivity of 73% and specificity of 100%. The results suggest that a rapid assay using the magnetometer technology detects specific anti-PRRSV antibody in pig serum. The magneto-immunoassay is suitable for use as a rapid ‘on-site’ method for the serological detection of PRRSV infection

Longitudinal Assessment of Cortical Excitability in Children and Adolescents With Mild Traumatic Brain Injury and Persistent Post-concussive Symptoms

Introduction: Symptoms following a mild traumatic brain injury (mTBI) usually resolve quickly but may persist past 3 months in up to 15% of children. Mechanisms of mTBI recovery are poorly understood, but may involve alterations in cortical neurophysiology. Transcranial Magnetic Stimulation (TMS) can non-invasively investigate such mechanisms, but the time course of neurophysiological changes in mTBI are unknown.Objective/Hypothesis: To determine the relationship between persistent post-concussive symptoms (PPCS) and altered motor cortex neurophysiology over time.Methods: This was a prospective, longitudinal, controlled cohort study comparing children (8–18 years) with mTBI (symptomatic vs. asymptomatic) groups to controls. Cortical excitability was measured using TMS paradigms at 1 and 2 months post injury. The primary outcome was the cortical silent period (cSP). Secondary outcomes included short interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval cortical inhibition (LICI). Generalized linear mixed model analyses were used to evaluate the effect of group and time on neurophysiological parameters.Results: One hundred seven participants (median age 15.1, 57% female) including 78 (73%) with symptomatic PPCS and 29 with asymptomatic mTBI, were compared to 26 controls. Cortical inhibition (cSP and SICI) was reduced in the symptomatic group compared to asymptomatic group and tended to increase over time. Measures of cortical facilitation (SICF and ICF) were increased in the asymptomatic group and decreased over time. TMS was well tolerated with no serious adverse events.Conclusions: TMS-assessed cortical excitability is altered in children following mild TBI and is dependent on recovery trajectory. Our findings support delayed return to contact sports in children even where clinical symptoms have resolved

Metastatic Tumor Evolution and Organoid Modeling Implicate TGFBR2 as a Cancer Driver in Diffuse Gastric Cancer

Background: Gastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis. Results: Both the primary tumor and ovarian metastasis have common biallelic loss-of-function of both the CDH1 and TP53 tumor suppressors, indicating a common genetic origin. While the primary tumor exhibits amplification of the Fibroblast growth factor receptor 2 (FGFR2) gene, the metastasis notably lacks FGFR2 amplification but rather possesses unique biallelic alterations of Transforming growth factor-beta receptor 2 (TGFBR2), indicating the divergent in vivo evolution of a TGFBR2-mutant metastatic clonal population in this patient. As TGFBR2 mutations have not previously been functionally validated in gastric cancer, we modeled the metastatic potential of TGFBR2 loss in a murine three-dimensional primary gastric organoid culture. The Tgfbr2 shRNA knockdown within Cdh1-/-; Tp53-/- organoids generates invasion in vitro and robust metastatic tumorigenicity in vivo, confirming Tgfbr2 metastasis suppressor activity. Conclusions: We document the metastatic differentiation and genetic heterogeneity of diffuse gastric cancer and reveal the potential metastatic role of TGFBR2 loss-of-function. In support of this study, we apply a murine primary organoid culture method capable of recapitulating in vivo metastatic gastric cancer. Overall, we describe an integrated approach to identify and functionally validate putative cancer drivers involved in metastasi

The Spitzer Survey of Stellar Structure in Galaxies (S^4G)

The Spitzer Survey of Stellar Structure in Galaxies S^4G is an Exploration Science Legacy Program approved for the Spitzer post-cryogenic mission. It is a volume-, magnitude-, and size-limited (d < 40 Mpc, |b| > 30 degrees, m_(Bcorr) < 15.5, D25>1') survey of 2,331 galaxies using IRAC at 3.6 and 4.5 microns. Each galaxy is observed for 240 s and mapped to > 1.5 x D25. The final mosaicked images have a typical 1 sigma rms noise level of 0.0072 and 0.0093 MJy / sr at 3.6 and 4.5 microns, respectively. Our azimuthally-averaged surface brightness profile typically traces isophotes at mu_3.6 (AB) (1 sigma) ~ 27 mag arcsec^-2, equivalent to a stellar mass surface density of ~ 1 Msun pc^-2. S^4G thus provides an unprecedented data set for the study of the distribution of mass and stellar structures in the local Universe. This paper introduces the survey, the data analysis pipeline and measurements for a first set of galaxies, observed in both the cryogenic and warm mission phase of Spitzer. For every galaxy we tabulate the galaxy diameter, position angle, axial ratio, inclination at mu_3.6 (AB) = 25.5 and 26.5 mag arcsec^-2 (equivalent to ~ mu_B (AB) =27.2 and 28.2 mag arcsec^-2, respectively). These measurements will form the initial S^4G catalog of galaxy properties. We also measure the total magnitude and the azimuthally-averaged radial profiles of ellipticity, position angle, surface brightness and color. Finally, we deconstruct each galaxy using GALFIT into its main constituent stellar components: the bulge/spheroid, disk, bar, and nuclear point source, where necessary. Together these data products will provide a comprehensive and definitive catalog of stellar structures, mass and properties of galaxies in the nearby Universe.Comment: Accepted for Publication in PASP, 14 pages, 13 figure

CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women with Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial

Background Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated the clinical relevance of CYP2D6 polymorphisms. Methods We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the randomized, phase III double-blind Breast International Group (BIG) 1-98 trial between March 1998 and May 2003 and received tamoxifen and/or letrozole treatment. Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods. Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor, intermediate, and extensive metabolizers (PM, IM, and EM, respectively; n = 4393 patients). Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval (referred to as recurrence) and treatment-induced hot flushes according to randomized endocrine treatment and previous chemotherapy were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy (P = .35). PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype (PM or IM vs EM, HR of recurrence = 0.86, 95% CI = 0.60 to 1.24). CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes (P = .020). Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype (PM vs EM, HR of hot flushes = 1.24, 95% CI = 0.96 to 1.59; IM vs EM, HR of hot flushes = 1.23, 95% CI = 1.05 to 1.43). Conclusions CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes, contrary to the hypothesis. The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxife

Natural images from the birthplace of the human eye

Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about 5000 six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon. Images are available in the raw RGB format and in grayscale. Images are also available in units relevant to the physiology of human cone photoreceptors, where pixel values represent the expected number of photoisomerizations per second for cones sensitive to long (L), medium (M) and short (S) wavelengths. This database is distributed under a Creative Commons Attribution-Noncommercial Unported license to facilitate research in computer vision, psychophysics of perception, and visual neuroscience.Comment: Submitted to PLoS ON

Torus and AGN properties of nearby Seyfert galaxies: Results from fitting IR spectral energy distributions and spectroscopy

We used the CLUMPY torus models and a Bayesian approach to fit the infrared spectral energy distributions (SEDs) and ground-based high-angular resolution mid-infrared spectroscopy of 13 nearby Seyfert galaxies. This allowed us to put tight constraints on torus model parameters such as the viewing angle, the radial thickness of the torus Y, the angular size of the cloud distribution sigma_torus, and the average number of clouds along radial equatorial rays N_0. The viewing angle is not the only parameter controlling the classification of a galaxy into a type 1 or a type 2. In principle type 2s could be viewed at any viewing angle as long as there is one cloud along the line of sight. A more relevant quantity for clumpy media is the probability for an AGN photon to escape unabsorbed. In our sample, type 1s have relatively high escape probabilities, while in type 2s, as expected, tend to be low. Our fits also confirmed that the tori of Seyfert galaxies are compact with torus model radii in the range 1-6pc. The scaling of the models to the data also provided the AGN bolometric luminosities, which were found to be in good agreement with estimates from the literature. When we combined our sample of Seyfert galaxies with a sample of PG quasars from the literature to span a range of L_bol(AGN)~10^{43}-10^{47}erg/s, we found plausible evidence of the receding torus. That is, there is a tendency for the torus geometrical covering factor to be lower at high AGN luminosities than at low AGN luminosities. This is because at low AGN luminosities the tori appear to have wider angular sizes and more clouds along radial equatorial rays. We cannot, however rule out the possibility that this is due to contamination by extended dust structures not associated with the dusty torus at low AGN luminosities, since most of these in our sample are hosted in highly inclined galaxies. (Abridged)Comment: Accepted for publication in Ap