Multiobjective, preference-based search in acyclic OR-graphs

We consider the problem of determining a most preferred path from a start node to a goal node set in an acyclic OR-graph, given a multiattribute preference function, a multiobjective reward structure, and heuristic information about this reward structure. We present an algorithm which is shown to terminate with a most preferred path, given an admissible heuristic set. The algorithm illustrates how Artificial Intelligence techniques can be productively employed to solve multiobjective problems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30207/1/0000597.pd

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells

Abstract Introduction Previous studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells. Methods MUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells. Results Immunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis. Conclusions Our observations suggest that after an initial loss of MUC4 levels during the transition of normal breast tissue to primary tumor, the re-establishment of elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by promoting the acquisition of cellular properties associated with malignancy

Peat Bog Wildfire Smoke Exposure in Rural North Carolina Is Associated with Cardiopulmonary Emergency Department Visits Assessed through Syndromic Surveillance

Background: In June 2008, burning peat deposits produced haze and air pollution far in excess of National Ambient Air Quality Standards, encroaching on rural communities of eastern North Carolina. Although the association of mortality and morbidity with exposure to urban air pollution is well established, the health effects associated with exposure to wildfire emissions are less well understood. Objective: We investigated the effects of exposure on cardiorespiratory outcomes in the population affected by the fire. Methods: We performed a population-based study using emergency department (ED) visits reported through the syndromic surveillance program NC DETECT (North Carolina Disease Event Tracking and Epidemiologic Collection Tool). We used aerosol optical depth measured by a satellite to determine a high-exposure window and distinguish counties most impacted by the dense smoke plume from surrounding referent counties. Poisson log-linear regression with a 5-day distributed lag was used to estimate changes in the cumulative relative risk (RR). Results: In the exposed counties, significant increases in cumulative RR for asthma [1.65 (95% confidence interval, 1.25–2.1)], chronic obstructive pulmonary disease [1.73 (1.06–2.83)], and pneumonia and acute bronchitis [1.59 (1.07–2.34)] were observed. ED visits associated with cardiopulmonary symptoms [1.23 (1.06–1.43)] and heart failure [1.37 (1.01–1.85)] were also significantly increased. Conclusions: Satellite data and syndromic surveillance were combined to assess the health impacts of wildfire smoke in rural counties with sparse air-quality monitoring. This is the first study to demonstrate both respiratory and cardiac effects after brief exposure to peat wildfire smoke

Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells

In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in vivo exposure of a living person. The goal of the present study was to compare the dose and effect of O3 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled O3 (18O3, 0.3 ppm, 2 h) while exercising intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1 h post exposure for in vivo data whereas in vitro data were obtained from primary cultures of human bronchial epithelial cells exposed to 0.25–1.0 ppm 18O3 for 2 h. The O3 dose to the cells was defined as the level of 18O incorporation and the O3 effect as the fold increase in expression of inflammatory marker genes (IL-8 and COX-2). Dose and effect in cells removed from in vivo exposed subjects were lower than in cells exposed to the same 18O3 concentration in vitro suggesting upper airway O3 scrubbing in vivo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher O3 dose than cells in the bronchus. We conclude that the methods used herein show promise for replicating and comparing the in vivo dose and effect of O3 in an in vitro system

Mammal collections of the Western Hemisphere: A survey and directory of collections

As a periodic assessment of the mammal collection resource, the Systematic Collections Committee (SCC) of the American Society of Mammalogists undertakes decadal surveys of the collections held in the Western Hemisphere. The SCC surveyed 429 collections and compiled a directory of 395 active collections containing 5,275,155 catalogued specimens. Over the past decade, 43 collections have been lost or transferred and 38 new or unsurveyed collections were added. Growth in number of total specimens, expansion of genomic resource collections, and substantial gains in digitization and web accessibility were documented, as well as slight shifts in proportional representation of taxonomic groups owing to increasingly balanced geographic representation of collections relative to previous surveys. While we find the overall health of Western Hemisphere collections to be adequate in some areas, gaps in spatial and temporal coverage and clear threats to long-term growth and vitality of these resources have also been identified. Major expansion of the collective mammal collection resource along with a recommitment to appropriate levels of funding will be required to meet the challenges ahead for mammalogists and other users, and to ensure samples are broad and varied enough that unanticipated future needs can be powerfully addressed. © 2018 The Author(s)

Isolation of microvillar microfilaments and associated transmembrane complex from ascites tumor cell microvilli

The association of microvillar microfilaments with the microvillar membrane actin-containing transmembrane complex of MAT-C1 13762 ascites tumor cell microvilli has been investigated by differential centrifugation, gel electrophoresis and electron microscopy of detergent extracts of the isolated microvilli. Several methods have been used to reduce breakdown and solubilization of the microfilament core actin during the detergent extractions for preparation of microvillar core microfilaments. Gel electrophoresis of differential centrifugation fractions demonstrated that over 70% of the total microvillus actin could be pelleted with microfilament cores at 10 000 g under extraction conditions which reduce filament breakdown. Transmission electron microscopy (TEM) of all of the core preparations showed arrays of microfilaments and small microfilament bundles. The major protein components of the microfilament cores, observed by sodium dodecyl sulfate (SDS) electrophoresis, were actin and α-actinin. Among the less prominent polypeptide components was a 58 000 Dalton polypeptide (58 K), previously identified as a member of the MAT-C1 transmembrane complex. This three-component complex contains, in addition to 58 K, actin associated directly and stably with a cell surface glycoprotein (Carraway, CAC, Jung, G & Carraway, K L, Proc. natl acad. sci. US 80 (1983) 430). [12] Evidence that the apparent association of complex with the microfilament core was not due simply to co-sedimentation was provided by myosin affinity precipitation. These results provide further evidence that the transmembrane complex is a site for the interaction of microfilaments with the microvillar plasma membrane