314 research outputs found

    Particle Size Distribution in Aluminum Manufacturing Facilities.

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    As part of exposure assessment for an ongoing epidemiologic study of heart disease and fine particle exposures in aluminum industry, area particle samples were collected in production facilities to assess instrument reliability and particle size distribution at different process areas. Personal modular impactors (PMI) and Minimicro-orifice uniform deposition impactors (MiniMOUDI) were used. The coefficient of variation (CV) of co-located samples was used to evaluate the reproducibility of the samplers. PM2.5 measured by PMI was compared to PM2.5 calculated from MiniMOUDI data. Mass median aerodynamic diameter (MMAD) and concentrations of sub-micrometer (PM1.0) and quasi-ultrafine (PM0.56) particles were evaluated to characterize particle size distribution. Most of CVs were less than 30%. The slope of the linear regression of PMI_PM2.5 versus MiniMOUDI_PM2.5 was 1.03 mg/m3 per mg/m3 (± 0.05), with correlation coefficient of 0.97 (± 0.01). Particle size distribution varied substantively in smelters, whereas it was less variable in fabrication units with significantly smaller MMADs (arithmetic mean of MMADs: 2.59 μm in smelters vs. 1.31 μm in fabrication units, p = 0.001). Although the total particle concentration was more than two times higher in the smelters than in the fabrication units, the fraction of PM10 which was PM1.0 or PM0.56 was significantly lower in the smelters than in the fabrication units (p < 0.001). Consequently, the concentrations of sub-micrometer and quasi-ultrafine particles were similar in these two types of facilities. It would appear, studies evaluating ultrafine particle exposure in aluminum industry should focus on not only the smelters, but also the fabrication facilities

    Ischemic Heart Disease Incidence in Relation to Fine versus Total Particulate Matter Exposure in a U.S. Aluminum Industry Cohort.

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    Ischemic heart disease (IHD) has been linked to exposures to airborne particles with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient environment and in occupational settings. Routine industrial exposure monitoring, however, has traditionally focused on total particulate matter (TPM). To assess potential benefits of PM2.5 monitoring, we compared the exposure-response relationships between both PM2.5 and TPM and incidence of IHD in a cohort of active aluminum industry workers. To account for the presence of time varying confounding by health status we applied marginal structural Cox models in a cohort followed with medical claims data for IHD incidence from 1998 to 2012. Analyses were stratified by work process into smelters (n = 6,579) and fabrication (n = 7,432). Binary exposure was defined by the 10th-percentile cut-off from the respective TPM and PM2.5 exposure distributions for each work process. Hazard Ratios (HR) comparing always exposed above the exposure cut-off to always exposed below the cut-off were higher for PM2.5, with HRs of 1.70 (95% confidence interval (CI): 1.11-2.60) and 1.48 (95% CI: 1.02-2.13) in smelters and fabrication, respectively. For TPM, the HRs were 1.25 (95% CI: 0.89-1.77) and 1.25 (95% CI: 0.88-1.77) for smelters and fabrication respectively. Although TPM and PM2.5 were highly correlated in this work environment, results indicate that, consistent with biologic plausibility, PM2.5 is a stronger predictor of IHD risk than TPM. Cardiovascular risk management in the aluminum industry, and other similar work environments, could be better guided by exposure surveillance programs monitoring PM2.5

    Paternal Smoking and Risk of Childhood Acute Lymphoblastic Leukemia: Systematic Review and Meta-Analysis

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    Objective. To investigate the association between paternal smoking and childhood acute lymphoblastic leukemia (ALL). Method. We identified 18 published epidemiologic studies that reported data on both paternal smoking and childhood ALL risk. We performed a meta-analysis and analyzed dose-response relationships on ALL risk for smoking during preconception, during pregnancy, after birth, and ever smoking. Results. The summary odds ratio (OR) of childhood ALL associated with paternal smoking was 1.11 (95% Confidence Interval (CI): 1.05–1.18, I2 = 18%) during any time period, 1.25 (95% CI: 1.08–1.46, I2 = 53%) preconception; 1.24 (95% CI: 1.07–1.43, I2 = 54%) during pregnancy, and 1.24 (95% CI: 0.96–1.60, I2 = 64%) after birth, with a dose-response relationship between childhood ALL and paternal smoking preconception or after birth. Conclusion. The evidence supports a positive association between childhood ALL and paternal ever smoking and at each exposure time period examined. Future epidemiologic studies should assess paternal smoking during well-defined exposure windows and should include biomarkers to assess smoking exposure and toxicological mechanisms

    The COPI Complex Functions in Nuclear Envelope Breakdown and Is Recruited by the Nucleoporin Nup153

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    AbstractNuclear envelope breakdown is a critical step in the cell cycle of higher eukaryotes. Although integral membrane proteins associated with the nuclear membrane have been observed to disperse into the endoplasmic reticulum at mitosis, the mechanisms involved in this reorganization remain to be fully elucidated. Here, using Xenopus extracts, we report a role for the COPI coatomer complex in nuclear envelope breakdown, implicating vesiculation as an important step. We have found that a nuclear pore protein, Nup153, plays a critical role in directing COPI to the nuclear membrane at mitosis and that this event provides feedback to other aspects of nuclear disassembly. These results provide insight into how key steps in nuclear division are orchestrated

    Copulation defective mutants of C. elegans

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    To identify genes involved in male copulatory behavior, we carried out an F2 clonal screen in a him-5 mutant background. We identified 20 mutations that affect male mating behavior without causing gross defects in morphology. ​ Male mating in C. elegans comprises at least five steps (Liu and Sternberg, 1995). (l) The male responds to the hermaphrodite by backing his tail along the length of the hermaphrodite, (2) he turns over or under her body before reaching the head or tail, (3) he locates the vulva with his tail, at which point he stops backing, (4) he inserts his spicules into the vulva, and (5) he transfers sperm. To study the genetic basis for male mating behavior, we are isolating and characterizing Copulation Defective (Cod) mutations. We screened for mutant strains defective in this behavior using the screen described by Hodgkin (1983). him-5(e1490) worms are mutagenized with ethyl methane sulfonate (EMS); 20 P0 L4 hermaphrodites are picked singly to Petri plates; ten F1 worms are picked per mutagenized P0; and ten F2 L4 hermaphrodites are singled per P0 and their male progeny tested for mating efficiency via a qualitative mating test (six males crossed with six unc-52(e444) hermaphrodites, which are paralyzed at adulthood (Brenner, 1974). Mutants with phenotypes that are likely to reduce mating efficiency in a non-specific manner (such as those causing an Unc, Dpy, or Lon phenotype) were discarded. Those strains that appear morphologically normal under the dissecting microscope yet fail to mate or mate at a very low efficiency (1-5% cross progeny compared to wild type) were screened under Nomarski optics for defects in male reproductive structures. We screened over 3000 haploid genomes, and picked over 100 strains with reproduction defects. Nineteen strains were successfully backcrossed, which represents about 25% of the total strains attempted. This result suggests that most strains harbor two or more mutations that contribute to the mating-deficiency defect. Preliminary analysis of behavior suggests that every major step in the wild-type mating pathway has at least one corresponding Cod mutation blocking the behavior, with several mutations blocking at the spicule insertion step. The screen also yielded morphological mutants, whose phenotypes include crumpled spicules, abnormal rays, and a gonad migration defect; some of these will be described elsewhere (Chamberlin & Sternberg; micropublication in preparation)

    Restaurant and Bar Owners’ Exposure to Secondhand Smoke and Attitudes Regarding Smoking Bans in Five Chinese Cities

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    Despite the great progress made towards smoke-free environments, only 9% of countries worldwide mandate smoke-free restaurants and bars. Smoking was generally not regulated in restaurants and bars in China before 2008. This study was designed to examine the public attitudes towards banning smoking in these places in China. A convenience sample of 814 restaurants and bars was selected in five Chinese cities and all owners of these venues were interviewed in person by questionnaire in 2007. Eighty six percent of current nonsmoking subjects had at least one-day exposure to secondhand smoke (SHS) at work in the past week. Only 51% of subjects knew SHS could cause heart disease. Only 17% and 11% of subjects supported prohibiting smoking completely in restaurants and in bars, respectively, while their support for restricting smoking to designated areas was much higher. Fifty three percent of subjects were willing to prohibit or restrict smoking in their own venues. Of those unwilling to do so, 82% thought smoking bans would reduce revenue, and 63% thought indoor air quality depended on ventilation rather than smoking bans. These results showed that there was support for smoking bans among restaurant or bar owners in China despite some knowledge gaps. To facilitate smoking bans in restaurants and bars, it is important to promote health education on specific hazards of SHS, provide country-specific evidence on smoking bans and hospitality revenues, and disseminate information that restricting smoking and ventilation alone cannot eliminate SHS hazards

    On State Fusers Over Long-Haul Sensor Networks

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    Abstract-We consider a network of sensors wherein the state estimates are sent from sensors to a fusion center to generate a global state estimate. The underlying fusion algorithm affects the performance measure QCC (τ ) (with subscripts CC indicating the effects of the communications and computing quality) of the global state estimate computed within the allocated time τ . We present a probabilistic performance bound on QCC (τ ) as a function of the distributions of state estimates, communications parameters as well as the fusion algorithm. We present simulations of simplified scenarios to illustrate the qualitative effects of different fusers, and system-level simulations to complement the analytical results

    An improved method for undertaking limiting dilution assays for in vitro cloning of Plasmodium falciparum parasites

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    Abstract. Background: Obtaining single parasite clones is required for many techniques in malaria research. Cloning by limiting dilution using microscopy-based assessment for parasite growth is an arduous and labor-intensive process. An alternative method for the detection of parasite growth in limiting dilution assays is using a commercial ELISA histidine-rich protein II (HRP2) detection kit. Methods. Detection of parasite growth was undertaken using HRP2 ELISA and compared to thick film microscopy. An HRP2 protein standard was used to determine the detection threshold of the HRP2 ELISA assay, and a HRP2 release model was used to extrapolate the amount of parasite growth required for a positive result. Results: The HRP2 ELISA was more sensitive than microscopy for detecting parasite growth. The minimum level of HRP2 protein detection of the ELISA was 0.11ng/ml. Modeling of HRP2 release determined that 2,116 parasites are required to complete a full erythrocytic cycle to produce sufficient HRP2 to be detected by the ELISA. Under standard culture conditions this number of parasites is likely to be reached between 8 to 14 days of culture. Conclusions: This method provides an accurate and simple way for the detection of parasite growth in limiting dilution assays, reducing time and resources required in traditional methods. Furthermore the method uses spent culture media instead of the parasite-infected red blood cells, enabling culture to continue

    Imaging Trans-Cellular Neurexin-Neuroligin Interactions by Enzymatic Probe Ligation

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    Neurexin and neuroligin are transmembrane adhesion proteins that play an important role in organizing the neuronal synaptic cleft. Our lab previously reported a method for imaging the trans-synaptic binding of neurexin and neuroligin called BLINC (Biotin Labeling of INtercellular Contacts). In BLINC, biotin ligase (BirA) is fused to one protein while its 15-amino acid acceptor peptide substrate (AP) is fused to the binding partner. When the two fusion proteins interact across cellular junctions, BirA catalyzes the site-specific biotinylation of AP, which can be read out by staining with streptavidin-fluorophore conjugates. Here, we report that BLINC in neurons cannot be reproduced using the reporter constructs and labeling protocol previously described. We uncover the technical reasons for the lack of reproducibilty and then re-design the BLINC reporters and labeling protocol to achieve neurexin-neuroligin BLINC imaging in neuron cultures. In addition, we introduce a new method, based on lipoic acid ligase instead of biotin ligase, to image trans-cellular neurexin-neuroligin interactions in human embryonic kidney cells and in neuron cultures. This method, called ID-PRIME for Interaction-Dependent PRobe Incorporation Mediated by Enzymes, is more robust than BLINC due to higher surface expression of lipoic acid ligase fusion constructs, gives stronger and more localized labeling, and is more versatile than BLINC in terms of signal readout. ID-PRIME expands the toolkit of methods available to study trans-cellular protein-protein interactions in living systems.National Institutes of Health (U.S.) (DP1 OD003961
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