Summary Autophagy is a conserved catabolic process that plays a housekeeping role in eliminating protein aggregates and organelles and is activated during nutrient deprivation to generate metabolites and energy. Autophagy plays a significant role in tumorigenesis, although opposing context-dependent functions of autophagy in cancer have complicated efforts to target autophagy for therapeutic purposes. We demonstrate that autophagy inhibition reduces tumor cell migration and invasion in vitro and attenuates metastasis in vivo. Numerous abnormally large focal adhesions (FAs) accumulate in autophagy-deficient tumor cells, reflecting a role for autophagy in FA disassembly through targeted degradation of paxillin. We demonstrate that paxillin interacts with processed LC3 through a conserved LIR motif in the amino terminal end of paxillin and that this interaction is regulated by oncogenic SRC activity. Together, these data establish a function for autophagy in FA turnover, tumor cell motility and metastasis.
The performance of the 1.5-mm pulsed Doppler lidar, operated by the U.K. Universities Facility for Atmospheric Measurement (UFAM) over a 51-day continuous and unattended field deployment in southern England, is described and analyzed with a view to demonstrating the capabilities of the system for remote measurements of aerosols and velocities in the boundary layer. A statistical assessment of the vertical pointing mode in terms of the availability and errors in the data versus range is presented. Examples of lidar data are compared to theoretical predictions, radiosondes, the UFAM radar wind profiler, and an ultrasonic anemometer.
Abstract. In April-July 2008, intensive measurements were made of atmospheric composition and chemistry in Sabah, Malaysia, as part of the "Oxidant and particle photochemical processes above a South-East Asian tropical rainforCorrespondence to: C. N. Hewitt (n.hewitt@lancaster.ac.uk) est" (OP3) project. Fluxes and concentrations of trace gases and particles were made from and above the rainforest canopy at the Bukit Atur Global Atmosphere Watch station and at the nearby Sabahmas oil palm plantation, using both ground-based and airborne measurements. Here, the measurement and modelling strategies used, the characteristics of the sites and an overview of data obtained are described. Composition measurements show that the rainforest Published by Copernicus Publications on behalf of the European Geosciences Union. 170 C. N. Hewitt et al.: The OP3 project: introduction, rationale, location characteristics and tools site was not significantly impacted by anthropogenic pollution, and this is confirmed by satellite retrievals of NO 2 and HCHO. The dominant modulators of atmospheric chemistry at the rainforest site were therefore emissions of BVOCs and soil emissions of reactive nitrogen oxides. At the observed BVOC:NO x volume mixing ratio (∼100 pptv/pptv), current chemical models suggest that daytime maximum OH concentrations should be ca. 10 5 radicals cm −3 , but observed OH concentrations were an order of magnitude greater than this. We confirm, therefore, previous measurements that suggest that an unexplained source of OH must exist above tropical rainforest and we continue to interrogate the data to find explanations for this.
SUMMARYThe industrial revolution led to a rapid development of urban areas. This has continued unremittingly over the last 200 years or so. In most urban areas the surface properties are heterogeneous, which has significant implications for energy budgets, water budgets and weather phenomena within the part of the earth's atmosphere that humans live. In this paper I discuss the structure of the planetary boundary layer, confining our analysis to the region above the rooftops (canopy layer) up to around the level where clouds form. It is in this part of the atmosphere that most of the weather impacting our lives occurs, and where the buildings of our cities impact the weather.In this review, observations of the structure of the urban atmospheric boundary layer are discussed. In particular the use of Doppler lidar provides measurements above the canopy layer. The impact of high-rise buildings is considered.Urban morphology impacts energy fluxes and airflow leading to phenomena such as the urban heat island and convective rainfall initiation. I discuss in situ surface-based remote sensing and satellite measurements of these effects. Measurements have been used with simple and complex numerical models to understand the complexity and balance of the interactions involved. Cities have been found to be sometimes up to 10 degC warmer than the surrounding rural areas, and to cause large increases in rainfall amounts. However, there are situations in which urban aerosol may suppress precipitation.Although much progress has been made in understanding these impacts, our knowledge remains incomplete. These limitations are identified. As city living becomes even more the norm for large numbers of people, it is imperative that we ensure that urban effects on the weather are included in development plans for the built environment of the future.
OBJECTIVES: A 1993 large water-borne outbreak of Salmonella typhimurium infections in Gideon, Mo, a city of 1100 with an unchlorinated community water supply, was investigated to determine the source of contamination and the effectiveness of an order to boil water. METHODS: A survey of household members in Gideon and the surrounding township produced information on diarrheal illness, water consumption, and compliance with the boil water order. RESULTS: More than 650 persons were ill; 15 were hospitalized, and 7 died. Persons consuming city water were more likely to be ill (relative risk [RR] = 9.1, 95% confidence interval [CI] = 2.9, 28.4), and the attack rate increased with increased water consumption. S. typhimurium was recovered from samples taken from a city fire hydrant and a water storage tower. Persons in 31% (30/ 98) of city households had drunk unboiled water after being informed about the boil water order, including 14 individuals who subsequently became ill. Reasons for noncompliance included "not remembering" (44%) and "disbelieving" (25%) the order. CONCLUSIONS: Communities with deteriorating water systems risk widespread illness unless water supplies are properly operated and maintained. Effective education to improve compliance during boil water orders is needed.
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