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This paper considers a dynamic pricing problem over a finite horizon where demand for a product is a time‐varying linear function of price. It is assumed that at the start of the horizon there is a fixed amount of the product available. The decision problem is to determine the optimal price at each time period in order to maximize the total revenue generated from the sale of the product. In order to obtain structural results we formulate the decision problem as an optimal control problem and solve it using Pontryagin's principle. For those problems which are not easily solvable when formulated as an optimal control problem, we present a simple convergent algorithm based on Pontryagin's principle that involves solving a sequence of very small quadratic programming (QP) problems. We also consider the case where the initial inventory of the product is a decision variable. We then analyse the two‐product version of the problem where the linear demand functions are defined in the sense of Bertrand and we again solve the problem using Pontryagin's principle. A special case of the optimal control problem is solved by transforming it into a linear complementarity problem. For the two‐product problem we again present a simple algorithm that involves solving a sequence of small QP problems and also consider the case where the initial inventory levels are decision variables. Copyright © 2006 John Wiley & Sons, Ltd.  相似文献   
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The popular and scientific understanding of acquired immunodeficiency syndrome (AIDS) in the United States has been shaped by successive historical constructions or paradigms of disease. In the first paradigm, AIDS was conceived of as a "gay plague," by analogy with the sudden, devastating epidemics of the past. In the second, AIDS was normalized as a chronic disease to be managed medically over the long term. By examining and extending critiques of both paradigms, it is possible to discern the emergence of an alternative paradigm of AIDS as a collective chronic infectious disease and persistent pandemic. Each of these constructions of AIDS incorporates distinct views of the etiology, prevention, pathology, and treatment of disease; each tacitly promotes different conceptions of the proper allocation of individual and social responsibility for AIDS. This paper focuses on individualistic vs collective, and biomedical vs social and historical, understandings of disease. It analyzes the use of individualism as methodology and as ideology, criticizes some basic assumptions of the biomedical model, and discusses alternative strategies for scientific research, health policy, and disease prevention.  相似文献   
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This paper provides a characterization of the phonological system of a family of specifically language-impaired (SLI) individuals. Morphological and syntactic data from these same subjects have previously been presented in Gopnik and Crago (1991) and Guilfoyle (1991). Data were collected from eight subjects, all family members, ranging from 7 to 46 years of age. Language samples were obtained at two sessions, 17 months apart, and analysed according to a revised version of the phonological assessment procedures outlined in Ingram (1981, 1989). Results indicated that these SLI subjects acquired the phonological inventory of English following the normal developmental sequence, but at an extremely delayed rate. In contrast, these subjects never achieved adult competency in reproducing the complex syllable patterns of English, as evidenced by the fact that consonants in syllable-final position and clusters were particularly susceptible to deletion or substitution errors. It is argued that these data are consistent with a linguistically based account of this impairment, which is manifested in the phonological component by the inability to construct learned, language-specific rules.  相似文献   
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PURPOSE: To determine the toxicity, maximal tolerated dose, and clinical and immunologic response to autologous dendritic cells pulsed with melanoma-associated antigen gp100-derived G280-9V peptide. PATIENTS AND METHODS: Twelve HLA-A*0201(+) patients with advanced melanoma were administered dendritic cells pulsed with G280-9V peptide. Cohorts of three patients were administered 5 x 10(6), 15 x 10(6), and 50 x 10(6) cells i.v. every 3 weeks for six doses according to a dose escalation scheme. Three additional patients were treated at the highest dose. No additional cytokines or therapies were coadministered. The immunogenicity of G280-9V-pulsed dendritic cells was measured by IFN-gamma ELISPOT assay, tetramer assay, and (51)Cr release assay comparing prevaccination to postvaccination blood samples. Response to treatment was assessed by Response Evaluation Criteria in Solid Tumors. RESULTS: CD8(+) immunity to the native G280 was observed in 8 (67%) patients as measured by ELISPOT and in 12 (100%) patients as measured by tetramer assay. Of the 9 patients tested, 9 (100%) had measurable high-avidity CTL activity as defined by lysis of allogeneic melanoma lines, which coexpress HLA-A*0201 and gp100. The median follow-up of the entire cohort is 43.8 months. Two (17%) partial responses were observed and 3 (25%) patients had stable disease. The median survival of the treated population was 37.6 months. At this time, three patients are alive, including one patient who continues to respond without additional treatment. CONCLUSION: The high rate of immunization as measured by three independent assays and the occurrence of clinical regression support continued investigation of G280-9V peptide as a candidate epitope in melanoma vaccine formulations.  相似文献   
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From the plasma membrane of Thermus thermophilus HB8 we have partially purified a detergent-solubilized complex of cytochromes a and c1 that actively catalyzes the transfer of electrons from ascorbate via a redox dye to oxygen. The complex is composed of two types of polypeptides, with molecular weights of approximately 55,000 and 33,000. Quantitative analysis revealed the presence of heme a, heme c, and copper in a ratio of 2:1:2, with the heme a being present at 10 +/- 1.3 nmol/mg of protein. The heme c was shown to be associated with the molecular weight 33,000 peptide and is suggested to be of the c1 type. The optical and electron paramagnetic resonance properties of this complex were found to be similar to those of eukaryotic cytochrome oxidase, suggesting the following arrangement of chromophores: a magnetically isolated cytochrome c1 and an oxygen-reducing functional unit consisting of two heme a groups and two copper ions associated with one or more larger peptides.  相似文献   
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Consensus-recommendations for sirolimus in liver transplantation   总被引:2,自引:0,他引:2  
Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.  相似文献   
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