Functional Blockade of E-Selectin in Tumor-Associated Vessels Enhances Anti-Tumor Effect of Doxorubicin in Breast Cancer

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both tumor infiltrating T-lymphocytes and tumor associated-macrophages were skewed towards TH2 in DOX-treated residual breast tumors; however, ESTA suppressed these changes. This study suggests that DOX treatment instigates de novo intratumoral infiltration of immune cells through E-selectin, and functional blockade of E-selectin may reduce residual tumor burden as well as metastasis through suppression of TH2 shift

An Automated Image-Based Method for Rapid Analysis of Chlamydia Infection as a Tool for Screening Antichlamydial Agents

This is the published version. Copyright American Society for MicrobiologyA major limitation in the identification of novel antichlamydial compounds is the paucity of effective methods for large-scale compound screening. The immunofluorescence assay is the preferred approach for accurate quantification of the intracellular growth of Chlamydia. In this study, an immunofluorescence image-based method (termed image-based automated chlamydial identification and enumeration [iBAChIE]) was customized for fully automated quantification of Chlamydia infection using the freely available open-source image analysis software program CellProfiler and the complementary data exploration software program CellProfiler Analyst. The method yielded enumeration of different species and strains of Chlamydia highly comparably to the conventional manual methods while drastically reducing the analysis time. The inhibitory capability of established antichlamydial activity was also evaluated. Overall, these data support that iBAChIE is a highly effective tool for automated quantification of Chlamydia infection and assessment of antichlamydial activities of molecules. Furthermore, iBAChIE is expected to be amenable to high-throughput screening studies for inhibitory compounds and fluorescently labeled molecules to study host-pathogen interactions

Population-based study of ischemic stroke risk after trauma in children and young adults.

OBJECTIVE:To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort. METHODS:We electronically identified trauma patients (<50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression. RESULTS:From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation). CONCLUSIONS:Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected

The ACS Virgo Cluster Survey III. Chandra and HST Observations of Low-Mass X-Ray Binaries and Globular Clusters in M87

The ACIS instrument on board the Chandra X-ray Observatory has been used to carry out the first systematic study of low-mass X-ray binaries (LMXBs) in M87. We identify 174 X-ray point-sources, of which ~150 are likely LMXBs. This LMXB catalog is combined with deep F475W and F850LP images taken with ACS on HST to examine the connection between LMXBs and globular clusters in M87. Of the 1688 globular clusters in our catalog, f_X = 3.6 +- 0.5% contain a LMXB and we find that the metal-rich clusters are 3 +- 1 times more likely to harbor a LMXB than their metal-poor counterparts. In agreement with previous findings for other galaxies, we find that brighter, more metal-rich clusters are more likely to contain a LMXB. For the first time, however, we are able to demonstrate that the probability, p_X, that a given cluster will contain a LMXB depends sensitively on the dynamical properties of the host cluster. Specifically, we use the HST images to measure the half-light radius, concentration index and central density, \rho_0, for each globular, and define a parameter, \Gamma, which is related to the tidal capture and binary-neutron star exchange rate. Our preferred form for p_X is then p_X \propto \Gamma \rho_0^{-0.42\pm0.11} (Z/Z_{\odot})^{0.33\pm0.1}. We argue that if the form of p_X is determined by dynamical processes, then the observed metallicity dependence is a consequence of an increased number of neutron stars per unit mass in metal-rich globular clusters. Finally, we find no compelling evidence for a break in the luminosity distribution of resolved X-ray point sources. Instead, the LMXB luminosity function is well described by a power law with an upper cutoff at L_X ~ 10^39 erg/s. (abridged)Comment: 23 pages, 21 figures. Accepted for publication in ApJ. Also available at http://www.physics.rutgers.edu/~pcote/acs/publications.htm

The technologies of isolation: apocalypse and self in Kurosawa Kiyoshi's Kairo

In this investigation of the Japanese film Kairo, I contemplate how the horrors present in the film relate to the issue of self, by examining a number of interlocking motifs. These include thematic foci on disease and technology which are more intimately and inwardly focused that the film's conclusion first appears to suggest. The true horror here, I argue, is ontological: centred on the self and its divorcing from the exterior world, especially founded in an increased use of and reliance on communicative technologies. I contend that these concerns are manifested in Kairo by presenting the spread of technology as disease-like, infecting the city and the individuals who are isolated and imprisoned by their urban environment. Finally, I investigate the meanings of the apocalypse, expounding how it may be read as hopeful for the future rather than indicative of failure or doom

Sources and characteristics of summertime organic aerosol in the Colorado Front Range: perspective from measurements and WRF-Chem modeling

Abstract. The evolution of organic aerosols (OAs) and their precursors in the boundary layer (BL) of the Colorado Front Range during the Front Range Air Pollution and Photochemistry Éxperiment (FRAPPÉ, July–August 2014) was analyzed by in situ measurements and chemical transport modeling. Measurements indicated significant production of secondary OA (SOA), with enhancement ratio of OA with respect to carbon monoxide (CO) reaching 0.085±0.003 µg m−3 ppbv−1. At background mixing ratios of CO, up to  ∼  1.8 µg m−3 background OA was observed, suggesting significant non-combustion contribution to OA in the Front Range. The mean concentration of OA in plumes with a high influence of oil and natural gas (O&G) emissions was  ∼  40 % higher than in urban-influenced plumes. Positive matrix factorization (PMF) confirmed a dominant contribution of secondary, oxygenated OA (OOA) in the boundary layer instead of fresh, hydrocarbon-like OA (HOA). Combinations of primary OA (POA) volatility assumptions, aging of semi-volatile species, and different emission estimates from the O&G sector were used in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) simulation scenarios. The assumption of semi-volatile POA resulted in greater than a factor of 10 lower POA concentrations compared to PMF-resolved HOA. Including top-down modified O&G emissions resulted in substantially better agreements in modeled ethane, toluene, hydroxyl radical, and ozone compared to measurements in the high-O&G-influenced plumes. By including emissions from the O&G sector using the top-down approach, it was estimated that the O&G sector contributed to  <  5 % of total OA, but up to 38 % of anthropogenic SOA (aSOA) in the region. The best agreement between the measured and simulated median OA was achieved by limiting the extent of biogenic hydrocarbon aging and consequently biogenic SOA (bSOA) production. Despite a lower production of bSOA in this scenario, contribution of bSOA to total SOA remained high at 40–54 %. Future studies aiming at a better emissions characterization of POA and intermediate-volatility organic compounds (IVOCs) from the O&G sector are valuable

Chaotic Amplification of Neutrino Chemical Potentials by Neutrino Oscillations in Big Bang Nucleosynthesis

We investigate in detail the parameter space of active-sterile neutrino oscillations that amplifies neutrino chemical potentials at the epoch of Big Bang Nucleosynthesis. We calculate the magnitude of the amplification and show evidences of chaos in the amplification process. We also discuss the implications of the neutrino chemical potential amplification in the Big Bang Nucleosynthesis. It is shown that with a $\sim 1$ eV \nue, the amplification of its chemical potential by active-sterile neutrino oscillations can lower the effective number of neutrino species at Big Bang Nucleosynthesis to significantly below 3.Comment: Revtex 20 pages, 7 postscript figures. Also by ftp://astro.queensu.ca/pub/shi/ . Submitted to PR

Prostanoid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [644]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2α, PGH2, prostacyclin [PGI2] and thromboxane A2. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies

Spontaneous graft-induced dyskinesias are independent of 5-HT neurons and levodopa priming in a model of Parkinson's disease

Background The risk of graft-induced dyskinesias (GIDs) presents a major challenge in progressing cell transplantation as a therapy for Parkinson's disease. Current theories implicate the presence of grafted serotonin neurons, hotspots of dopamine release, neuroinflammation and established levodopa-induced dyskinesia. Objective To elucidate the mechanisms of GIDs. Methods Neonatally desensitized, dopamine denervated rats received intrastriatal grafts of human embryonic stem cells (hESCs) differentiated into either ventral midbrain dopaminergic progenitor (vmDA) (n = 15) or ventral forebrain cells (n = 14). Results Of the eight rats with surviving grafts, two vmDA rats developed chronic spontaneous GIDs, which were observed at 30 weeks post-transplantation. GIDs were inhibited by D2-like receptor antagonists and not affected by 5-HT1A/1B/5-HT6 agonists/antagonists. Grafts in GID rats showed more microglial activation and lacked serotonin neurons. Conclusions These findings argue against current thinking that rats do not develop spontaneous GID and that serotonin neurons are causative, rather indicating that GID can be induced in rats by hESC-derived dopamine grafts and, critically, can occur independently of both previous levodopa exposure and grafted serotonin neurons

Does wage rank affect employees' well-being?

How do workers make wage comparisons? Both an experimental study and an analysis of 16,000 British employees are reported. Satisfaction and well-being levels are shown to depend on more than simple relative pay. They depend upon the ordinal rank of an individual's wage within a comparison group. “Rank” itself thus seems to matter to human beings. Moreover, consistent with psychological theory, quits in a workplace are correlated with pay distribution skewness