905 resultados para Supply and distribution
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Thesis (Ph.D.)--University of Washington, 2016-06
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Thesis (Ph.D.)--University of Washington, 2016-06
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This study investigated the relative contribution of ion-trapping, microsomal binding, and distribution of unbound drug as determinants in the hepatic retention of basic drugs in the isolated perfused rat liver. The ionophore monensin was used to abolish the vesicular proton gradient and thus allow an estimation of ion-trapping by acidic hepatic vesicles of cationic drugs. In vitro microsomal studies were used to independently estimate microsomal binding and metabolism. Hepatic vesicular ion-trapping, intrinsic elimination clearance, permeability-surface area product, and intracellular binding were derived using a physiologically based pharmacokinetic model. Modeling showed that the ion-trapping was significantly lower after monensin treatment for atenolol and propranolol, but not for antipyrine. However, no changes induced by monensin treatment were observed in intrinsic clearance, permeability, or binding for the three model drugs. Monensin did not affect binding or metabolic activity in vitro for the drugs. The observed ion-trapping was similar to theoretical values estimated using the pHs and fractional volumes of the acidic vesicles and the pK(a) values of drugs. Lipophilicity and pK(a) determined hepatic drug retention: a drug with low pK(a) and low lipophilicity (e.g., antipyrine) distributes as unbound drug, a drug with high pK(a) and low lipophilicity (e.g., atenolol) by ion-trapping, and a drug with a high pK(a) and high lipophilicity (e.g., propranolol) is retained by ion-trapping and intracellular binding. In conclusion, monensin inhibits the ion-trapping of high pK(a) basic drugs, leading to a reduction in hepatic retention but with no effect on hepatic drug extraction.
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Background: In early 2001, Australia experienced a sudden, dramatic and;sustained decrease in heroin availability that was accompanied by sharp increases in price and decreases in street level purity-the so-called heroin shortage. These unprecedented changes occurred in a context of widespread treatment availability, which made it possible for the first time to examine the impact of a sharp reduction in heroin supply in New South Wales (NSW) on entry to and adherence with treatment for heroin dependence. Given the evidence of drug substitution by some users. the current paper also examines the effects of the shortage on entry to treatment for other forms of drug dependence. Methods: Interrupted time-series analysis of the number of persons entering opioid pharmacotherapy and other treatment modalities in NSW for heroin dependence and for the treatment for other types of drug dependence. Findings: The heroin shortage was associated with a reduction in the number of younger persons entering opioid pharmacotherapy. There was a dramatic decrease in the number of persons entering heroin withdrawal or assessment only treatment episodes. There appear to have been small improvements in adherence to and retention in heroin treatment after the reduction in heroin supply. Relatively small increases were observed in numbers being treated for cocaine dependence. Conclusions: In the context of good treatment provision, a reduction in heroin supply appeared to produce modest improvements in intermediate outcomes. Supply and demand reduction measures, when both are implemented successfully, may be complementary. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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Orientational fluorophores have been a useful tool in physical chemistry, biochemistry, and more recently structural biology due to the polarized nature of the light they emit and that fact that energy can be transferred between them. We present a practical scheme in which measurements of the intensity of emitted fluorescence can be used to determine limits on the mean and distribution of orientation of the absorption transition moment of membrane-bound. uorophores. We demonstrate how information about the orientation of. uorophores can be used to calculate the orientation factor k(2) required for use in FRET spectroscopy. We illustrate the method using images of AlexaFluor probes bound to MscL mechanosensitive transmembrane channel proteins in spherical liposomes.
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Predicting future need for water resources has traditionally been, at best, a crude mixture of art and science. This has prevented the evaluation of water need from being carried out in either a consistent or comprehensive manner. This inconsistent and somewhat arbitrary approach to water resources planning led to well publicised premature developments in the 1970's and 1980's but privatisation of the Water Industry, including creation of the Office of Water Services and the National Rivers Authority in 1989, turned the tide of resource planning to the point where funding of schemes and their justification by the Regulators could no longer be assumed. Furthermore, considerable areas of uncertainty were beginning to enter the debate and complicate the assessment It was also no longer appropriate to consider that contingencies would continue to lie solely on the demand side of the equation. An inability to calculate the balance between supply and demand may mean an inability to meet standards of service or, arguably worse, an excessive provision of water resources and excessive costs to customers. United Kingdom Water Industry Research limited (UKWlR) Headroom project in 1998 provided a simple methodology for the calculation of planning margins. This methodology, although well received, was not, however, accepted by the Regulators as a tool sufficient to promote resource development. This thesis begins by considering the history of water resource planning in the UK, moving on to discuss events following privatisation of the water industry post·1985. The mid section of the research forms the bulk of original work and provides a scoping exercise which reveals a catalogue of uncertainties prevalent within the supply-demand balance. Each of these uncertainties is considered in terms of materiality, scope, and whether it can be quantified within a risk analysis package. Many of the areas of uncertainty identified would merit further research. A workable, yet robust, methodology for evaluating the balance between water resources and water demands by using a spreadsheet based risk analysis package is presented. The technique involves statistical sampling and simulation such that samples are taken from input distributions on both the supply and demand side of the equation and the imbalance between supply and demand is calculated in the form of an output distribution. The percentiles of the output distribution represent different standards of service to the customer. The model allows dependencies between distributions to be considered, for improved uncertainties to be assessed and for the impact of uncertain solutions to any imbalance to be calculated directly. The method is considered a Significant leap forward in the field of water resource planning.
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The changing business environment has sharpened the focus on the need for robust approaches to supply chain management (SCM) and the improvement of supply chain capability and performance. This is particularly the case in Ireland, which has the natural disadvantage of a location peripheral to significant markets and sources of raw materials which results in relatively high transport and distribution costs. Therefore, in order to gain insights into current levels of diffusion of SCM, a survey was conducted among 776 firms in the Republic of Ireland. The empirical results suggest that there is a need for more widespread adoption of SCM among Irish firms. This is particularly the case in relation to the four main elements of SCM excellence reported in this paper. The design of supply chain solutions is a highly skilled, knowledge-intensive and complex activity, reflected in a shift from 'box moving' to the design and implementation of customised supply chain solutions. Education and training needs to be addressed by stimulating the development of industry-relevant logistics and SCM resources and skills.
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This paper discusses demand and supply chain management and examines how artificial intelligence techniques and RFID technology can enhance the responsiveness of the logistics workflow. This proposed system is expected to have a significant impact on the performance of logistics networks by virtue of its capabilities to adapt unexpected supply and demand changes in the volatile marketplace with the unique feature of responsiveness with the advanced technology, Radio Frequency Identification (RFID). Recent studies have found that RFID and artificial intelligence techniques drive the development of total solution in logistics industry. Apart from tracking the movement of the goods, RFID is able to play an important role to reflect the inventory level of various distribution areas. In today’s globalized industrial environment, the physical logistics operations and the associated flow of information are the essential elements for companies to realize an efficient logistics workflow scenario. Basically, a flexible logistics workflow, which is characterized by its fast responsiveness in dealing with customer requirements through the integration of various value chain activities, is fundamental to leverage business performance of enterprises. The significance of this research is the demonstration of the synergy of using a combination of advanced technologies to form an integrated system that helps achieve lean and agile logistics workflow.
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In recent years, offshoring and outsourcing have transformed fundamentally nationally based auto sectors into global networks of design, production and distribution across the global value chains coordinated by the major automotive Original Equipment Manufacturers (OEMs). As manufacturing activities tended to be shifted to low-labour cost locations in Asia, Africa and Latin America, high-end design, R&D, product development have stayed anchored mostly to high-cost and high knowledge-intensive home economy locations (perhaps with the except of some design and styling activities which are often located in major end markets around the world. However, very recently the weaknesses of and risks inherent in such global value chains (GVCs) have been exposed, triggering attempts to rethink their nature and also raising possibilities to reshore some manufacturing activities to home countries. A combination of a more competitive exchange rate (despite the very recent appreciation of sterling), increased transport costs, rising wages in key areas of China, and a greater awareness of supply chain resilience have all contributed to a perceived change in some business fundamentals. The potential for some supply chain relocalisation also links in with the servitisation of manufacturing including the auto sector and shift to a hybrid model where manufacturing and services are increasingly intertwined. However, there are limits as to how far this can go and these raise some important questions and issues over the possible role for industrial policy.
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Vendor-managed inventory (VMI) is a widely used collaborative inventory management policy in which manufacturers manages the inventory of retailers and takes responsibility for making decisions related to the timing and extent of inventory replenishment. VMI partnerships help organisations to reduce demand variability, inventory holding and distribution costs. This study provides empirical evidence that significant economic benefits can be achieved with the use of a genetic algorithm (GA)-based decision support system (DSS) in a VMI supply chain. A two-stage serial supply chain in which retailers and their supplier are operating VMI in an uncertain demand environment is studied. Performance was measured in terms of cost, profit, stockouts and service levels. The results generated from GA-based model were compared to traditional alternatives. The study found that the GA-based approach outperformed traditional methods and its use can be economically justified in small- and medium-sized enterprises (SMEs).
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In this study, I determined the identity, taxonomic placement, and distribution of digenetic trematodes parasitizing the snails Pomacea paludosa and Planorbella duryi at Pa-hay-okee, Everglades National Park. I also characterized temporal and geographic variation in the probability of parasite infection for these snails based on two years of sampling. Although studies indicate that digenean parasites may have important effects both on individual species and the structure of communities, there have been no studies of digenean parasitism on snails within the Everglades ecosystem. For example, the endangered Everglade Snail Kite, a specialist that feeds almost exclusively on Pomacea paludosa, and is known to be a definitive host of digenean parasites, may suffer direct and indirect effects from consumption of parasitized apple snails. Therefore, information on the diversity and abundance of parasites harbored in snail populations in the Everglades should be of considerable interest for management and conservation of wildlife. Juvenile digeneans (cercariae) representing 20 species were isolated from these two snails, representing a quadrupling of the number of species known. Species were characterized based on morphological, morphometric, and sequence data (18S rDNA, COI, and ITS). Species richness of shed cercariae from P. duryi was greater than P. paludosa, with 13 and 7 species respectively. These species represented 14 families. P. paludosa and P. duryi had no digenean species in common. Probability of digenean infection was higher for P. duryi than P. paludosa and adults showed a greater risk of infection than juveniles for both of these snails. Planorbella duryi showed variation in probability of infection between sampling sites and hydrological seasons. The number of unique combinations of multi-species infections was greatest among P. duryi individuals, while the overall percentage of multi-species infections was greatest in P. paludosa. Analyses of six frequently-observed multiple infections from P. duryi suggest the presence of negative interactions, positive interactions, and neutral associations between larval digeneans. These results should contribute to an understanding of the factors controlling the abundance and distribution of key species in the Everglades ecosystem and may in particular help in the management and recovery planning for the Everglade Snail Kite.
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Lake Okeechobee, Florida, located in the middle of the larger Kissimmee River-Lake Okeechobee-Everglades ecosystem in South Florida, serves a variety of ecosystem and water management functions including fish and wildlife habitat, flood control, water supply, and source water for environmental restoration. As a result, the ecological status of Lake Okeechobee plays a significant role in defining the overall success of the greater Everglades ecosystem restoration initiative. One of the major ecological indicators of Lake Okeechobee condition focuses on the near-shore and littoral zone regions as characterized by the distribution and abundance of submerged aquatic vegetation (SAV) and giant bulrush (Scirpus californicus(C.A. Mey.) Steud.). The objective of this study is to present a stoplight restoration report card communication system, common to all 11 indicators noted in this special journal issue, as a means to convey the status of SAV and bulrush in Lake Okeechobee. The report card could be used by managers, policy makers, scientists and the public to effectively evaluate and distill information about the ecological status in South Florida. Our assessment of the areal distribution of SAV in Lake Okeechobee is based on a combination of empirical SAV monitoring and output from a SAV habitat suitability model. Bulrush status in the lake is related to a suitability index linked to adult survival and seedling establishment metrics. Overall, presentation of these performance metrics in a stoplight format enables an evaluation of how the status of two major components of Lake Okeechobee relates to the South Florida restoration program, and how the status of the lake influences restoration efforts in South Florida.
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The composition and distribution of diatom algae inhabiting estuaries and coasts of the subtropical Americas are poorly documented, especially relative to the central role diatoms play in coastal food webs and to their potential utility as sentinels of environmental change in these threatened ecosystems. Here, we document the distribution of diatoms among the diverse habitat types and long environmental gradients represented by the shallow topographic relief of the South Florida, USA, coastline. A total of 592 species were encountered from 38 freshwater, mangrove, and marine locations in the Everglades wetland and Florida Bay during two seasonal collections, with the highest diversity occurring at sites of high salinity and low water column organic carbon concentration (WTOC). Freshwater, mangrove, and estuarine assemblages were compositionally distinct, but seasonal differences were only detected in mangrove and estuarine sites where solute concentration differed greatly between wet and dry seasons. Epiphytic, planktonic, and sediment assemblages were compositionally similar, implying a high degree of mixing along the shallow, tidal, and storm-prone coast. The relationships between diatom taxa and salinity, water total phosphorus (WTP), water total nitrogen (WTN), and WTOC concentrations were determined and incorporated into weighted averaging partial least squares regression models. Salinity was the most influential variable, resulting in a highly predictive model (r apparent 2 = 0.97, r jackknife 2 = 0.95) that can be used in the future to infer changes in coastal freshwater delivery or sea-level rise in South Florida and compositionally similar environments. Models predicting WTN (r apparent 2 = 0.75, r jackknife 2 = 0.46), WTP (r apparent 2 = 0.75, r jackknife 2 = 0.49), and WTOC (r apparent 2 = 0.79, r jackknife 2 = 0.57) were also strong, suggesting that diatoms can provide reliable inferences of changes in solute delivery to the coastal ecosystem.
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The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.
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Automatic load transfer (ALT) on the 11 kV network is the process by which circuit breakers on the network are switched to form open points in order to feed load from different primary substations. Some of the potential benefits that may be gained from dynamically using ALT include maximising utilisation of existing assets, voltage regulation and reduced losses. One of the key issues, that has yet to be properly addressed in published research, is how to validate that the modelled benefits really exist. On an 11 kV distribution network where the load is continually changing and the load on each distribution substation is unlikely to be monitored - reduction in losses from moving the normally open point is particularly difficult to prove. This study proposes a method to overcome this problem and uses measured primary feeder data from two parts of the Western Power Distribution 11 kV Network under different configurations. The process of choosing the different configurations is based on a heuristic modelling method of locating minimum voltages to help reduce losses.