Genetic aspects of the effects of methylmercury in mice: The incidence of cleft palate and concentrations of adenosine 3′:5′ cyclic monophosphate in tongue and palatal shelf

Concentrations of adenosine 3′:5′ cyclic monophosphate (cAMP) were measured in the tongues and palates of 14.5-day-old fetuses from control and methylmercury-treated mothers of four inbred lines of mice which represent the four possible combinations of two H-2 alleles and two residual genetic backgrounds. The incidence of cleft palate in fetuses from control and methylmercury-treated mothers was also examined. The H-2 alleles significantly affected the degree of reduction of cAMP concentration in palates seen in fetuses from mothers treated with methylmercury. Neither the H-2 allele nor the residual genetic background played a role in the effect of methylmercury on cAMP concentrations in fetal tongues. The magnitude of increase in the incidence of cleft palate with methylmercury treatment was approximately the same for all lines. Thus, methylmercury-induced cleft palate may not be mediated by the reduction of cAMP. Finally, fetuses with cleft lip had increased palatal cAMP levels, whether or not they were from control or methylmercury treated mothers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38148/1/1420230315_ftp.pd

An Analysis of the Legal, Social, and Political Issues Raised by Asbestos Litigation

This Special Project examines the most important issues of the asbestos problem and advocates a congressional solution (1) to relieve the courts of the thousands of present and potential asbestos cases, (2) to protect future claimants\u27 rights to adequate compensation, and (3) to provide for equitable participation by all responsible parties, which, in addition to asbestos manufacturers,include the federal government, insurance companies, and the tobacco industry. The first six parts of the Special Project examine the various issues of asbestos litigation: theories of liability in products liability suits against asbestos manufacturers, causation,defenses, statutory limitations on actions, collateral estoppel, and punitive damages. The Special Project then discusses in parts VIII,IX, and X the methods used by asbestos manufacturers to attempt to spread their liability through asserting insurer liability, the exclusive remedy of workers\u27 compensation, and indemnity and contribution from the United States. Finally, the Special Project evaluates and analyzes recent developments in the asbestos litigation area, including proposals for federal legislative compensation programs and business alternatives available to asbestos manufacturers facing enormous asbestos-related liabilities... This Special Project critically has examined the most important issues concerning the asbestos problem. It has considered the complex legal, legislative, and social questions that society must confront in order to resolve this predicament. Only swift action by Congress in the form of a fair and comprehensive compensation scheme for victims of asbestos-related disabilities will initiate a solution to this difficult and pervasive problem

Endemic Human Coronaviruses in Hospitalized Adults with Community-Acquired Pneumonia: Results from the Louisville Pneumonia Study

Introduction: There are four endemic serotypes of human coronavirus (HCoV) that may cause community-acquired pneumonia (CAP) in humans. The clinical syndrome of CAP due to HCoVs is not well characterized. The objectives of this study were to evaluate incidence, epidemiology, and outcomes of CAP in adults due to HCoV and to compare them with CAP due to influenza. Methods: The Louisville Pneumonia Study (LPS) is a prospective observational study of hospitalized adult patients with CAP in the city of Louisville. Patients enrolled in the LPS in whom a respiratory viral panel polymerase chain reaction (PCR) was obtained were evaluated. Incidence, epidemiology, and outcomes were compared for patients with a positive PCR for HCoV versus patients with a positive PCR for influenza. Results: From 1,974 CAP patients with a PCR performed, HCoV was identified in 65 patients (3.3%), corresponding to the following serotypes: HCoV-229E in 12 patients, HCoV-OC43 in 38 patients, HCoV-NL63 in 6 patients and HCoV-HKU1 in 9 patients. No differences were observed in clinical presentation and early outcomes for patients with CAP due to HCoV compared to 244 patients with CAP due to influenza. One-year mortality after hospitalization was 32% for patients with CAP due to HCoV versus 13% for patients with CAP due to influenza. Conclusions: When compared to patients with CAP due to influenza, the clinical presentation of patients with CAP due to HCoV is similar, but these patients have significantly worse outcomes one year after hospitalization

Community-Acquired Pneumonia due to Endemic Human Coronaviruses compared to 2019 Novel Coronavirus: A Review

The human coronaviruses (HCoVs) are an important etiology of community-acquired respiratory tract infections. Community-acquired pneumonia (CAP) may be caused by serotypes of endemic HCoVs or highly pathogenic HCoVs. In this review we compared the clinical characteristic, management, outcomes, and infection control practices for patients with CAP due to endemic HCoVs versus patients with CAP due to 2019 novel coronavirus

Current Single Event Effects Compendium of Candidate Spacecraft Electronics for NASA

We present the results of single event effects (SEE) testing and analysis investigating the effects of radiation on electronics. This paper is a summary of test results

Composing first species counterpoint with a variable neighbourhood search algorithm

In this article, a variable neighbourhood search (VNS) algorithm is developed that can generate musical fragments consisting of a melody for the cantus firmus and the first species counterpoint. The objective function of the algorithm is based on a quantification of existing rules for counterpoint. The VNS algorithm developed in this article is a local search algorithm that starts from a randomly generated melody and improves it by changing one or two notes at a time. A thorough parametric analysis of the VNS reveals the significance of the algorithm's parameters on the quality of the composed fragment, as well as their optimal settings. A comparison of the VNS algorithm with a developed genetic algorithm shows that the VNS is more efficient. The VNS algorithm has been implemented in a user-friendly software environment for composition, called Optimuse. Optimuse allows a user to specify a number of characteristics such as length, key and mode. Based on this information, Optimuse 'composes' both cantus firmus and first species counterpoint. Alternatively, the user may specify a cantus firmus, and let Optimuse compose the accompanying first species counterpoint. © 2012 Taylor & Francis

Bringing 'place' back in: regional clusters, project governance, and new product outcomes

We examine new product outcomes in the context of regional clusters. Based on past research on marketing relationships, clusters, and social networks, we propose that the overall configuration of a cluster helps promote particular governance practices among its members. These practices have distinct value-creating properties, and when they are brought to bear on a specific new product development project within a cluster, they promote performance outcomes like product novelty and speed to market. Ultimately, these performance effects are reinforced by the configuration of the cluster itself. In general, we propose that new product outcomes follow from complex interactions between a cluster's macro-level configuration and its micro-level governance processes. More broadly, our framework points to the importance of geographical variables and to the role of “place” in marketing decision-making

Neutrophil Extracellular Trap (NET)-Mediated Killing of Pseudomonas aeruginosa: Evidence of Acquired Resistance within the CF Airway, Independent of CFTR

The inability of neutrophils to eradicate Pseudomonas aeruginosa within the cystic fibrosis (CF) airway eventually results in chronic infection by the bacteria in nearly 80 percent of patients. Phagocytic killing of P. aeruginosa by CF neutrophils is impaired due to decreased cystic fibrosis transmembrane conductance regulator (CFTR) function and virulence factors acquired by the bacteria. Recently, neutrophil extracellular traps (NETs), extracellular structures composed of neutrophil chromatin complexed with granule contents, were identified as an alternative mechanism of pathogen killing. The hypothesis that NET-mediated killing of P. aeruginosa is impaired in the context of the CF airway was tested. P. aeruginosa induced NET formation by neutrophils from healthy donors in a bacterial density dependent fashion. When maintained in suspension through continuous rotation, P. aeruginosa became physically associated with NETs. Under these conditions, NETs were the predominant mechanism of killing, across a wide range of bacterial densities. Peripheral blood neutrophils isolated from CF patients demonstrated no impairment in NET formation or function against P. aeruginosa. However, isogenic clinical isolates of P. aeruginosa obtained from CF patients early and later in the course of infection demonstrated an acquired capacity to withstand NET-mediated killing in 8 of 9 isolates tested. This resistance correlated with development of the mucoid phenotype, but was not a direct result of the excess alginate production that is characteristic of mucoidy. Together, these results demonstrate that neutrophils can kill P. aeruginosa via NETs, and in vitro this response is most effective under non-stationary conditions with a low ratio of bacteria to neutrophils. NET-mediated killing is independent of CFTR function or bacterial opsonization. Failure of this response in the context of the CF airway may occur, in part, due to an acquired resistance against NET-mediated killing by CF strains of P. aeruginosa

Fast and Not-so-Furious: Case Study of the Fast and Faint Type IIb SN 2021bxu

We present photometric and spectroscopic observations and analysis of SN~2021bxu (ATLAS21dov), a low-luminosity, fast-evolving Type IIb supernova (SN). SN~2021bxu is unique, showing a large initial decline in brightness followed by a short plateau phase. With $M_r = -15.93 \pm 0.16\, \mathrm{mag}$ during the plateau, it is at the lower end of the luminosity distribution of stripped-envelope supernovae (SE-SNe) and shows a distinct $\sim$10 day plateau not caused by H- or He-recombination. SN~2021bxu shows line velocities which are at least $\sim1500\,\mathrm{km\,s^{-1}}$ slower than typical SE-SNe. It is photometrically and spectroscopically similar to Type IIb SNe during the photospheric phases of evolution, with similarities to Ca-rich IIb SNe. We find that the bolometric light curve is best described by a composite model of shock interaction between the ejecta and an envelope of extended material, combined with a typical SN~IIb powered by the radioactive decay of $^{56}$Ni. The best-fit parameters for SN~2021bxu include a $^{56}$Ni mass of $M_{\mathrm{Ni}} = 0.029^{+0.004}_{-0.005}\,\mathrm{M_{\odot}}$, an ejecta mass of $M_{\mathrm{ej}} = 0.57^{+0.04}_{-0.03}\,\mathrm{M_{\odot}}$, and an ejecta kinetic energy of $K_{\mathrm{ej}} = 9.3^{+0.7}_{-0.6} \times 10^{49}\, \mathrm{erg}$. From the fits to the properties of the extended material of Ca-rich IIb SNe we find a trend of decreasing envelope radius with increasing envelope mass. SN~2021bxu has $M_{\mathrm{Ni}}$ on the low end compared to SE-SNe and Ca-rich SNe in the literature, demonstrating that SN~2021bxu-like events are rare explosions in extreme areas of parameter space. The progenitor of SN~2021bxu is likely a low mass He star with an extended envelope.Comment: 18 pages, 15 figures, submitted to MNRA

Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature