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This paper describes a general numerical method for the determination of rate constants that characterize the binding of a ligand L simultaneously and competitively to two different receptor molecules, R1 and R2. The experimental data consist of changes in the concentration of one receptor (e.g., R1) monitored over time. An example problem is represented by hirudin (L) binding to thrombin (R1) and to a chemical mutant of thrombin (R2). The published experimental data [Wedemeyer et al. (1997) Anal. Biochem. 248, 130-140], previously analyzed by using an appropriate algebraic method, were reanalyzed here by numerical integration [Kuzmic (1996) Anal. Biochem. 237, 260-273]. This general numerical method offers the following advantages. (1) It provides an estimate for the lower limit on feasible values of association rate constants. (2) It is many orders of magnitude more accurate. (3) It is easily extensible to more complicated reaction mechanisms. (4) It uses a simpler formalism and it is thus more accessible to nonmathematicians. (5) A suitable computer program for the analysis of competitive binding kinetics can be obtained via the Internet (http://www.biokin.com).  相似文献   
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Paech  B. Dorr  J. Koehler  M. 《Software, IEEE》2005,22(1):40-47
In complex, multiproject environments, communication is the key to successful requirements engineering. An information model helps with this problem by capturing stakeholders documents and responsibilities during RE. The information model effectively and practically ensures that stakeholders of dependent projects are mutually aware of critical communication needs. The author present the information model developed at Nokia Smart Traffic Products and shows how they defined it in a two-day workshop.  相似文献   
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Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.  相似文献   
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OBJECTIVE: To assess the results of laparoscopic splenectomy as a treatment for immune thrombocytopenic purpura (ITP). MATERIAL AND METHODS: We conducted a retrospective study of all patients who underwent laparoscopic splenectomy for ITP at our institution between August 1992 and May 1997. RESULTS: Of 27 patients who underwent attempted laparoscopic splenectomy for ITP at our institution during the study period, 26 had completion of the procedure without conversion to an open splenectomy. The median postoperative hospital stay was 1.5 days, and no postoperative deaths occurred. In one patient, pancreatitis developed postoperatively. In four patients, splenectomy failed--two initially and two subsequently--and reinstitution of medical therapy was necessary. The other patients have remained free of medication, and 19 patients have platelet counts greater than 100 x 10(9)/L. The 3-year actuarial success rate was 81.5%. Response to corticosteroid therapy preoperatively may be an indicator of success of splenectomy. CONCLUSION: Laparoscopic splenectomy is safe and allows prompt recovery. Long-term response rates are similar to those achieved with open splenectomy.  相似文献   
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A set of 20 2-cyanoaziridine-1-carboxamides was synthesized from 2-cyanoaziridine and appropriate isocyanates. These compounds were active against a variety of solid and hematological tumor cells in culture, including strains resistant to doxorubicin and mitoxantrone. Their potencies in these assays correlated with the lipophilicity of substituents. The N-phenyl derivative was more potent and equally effective to imexon, a cyclized 2-cyanoaziridine-1-carboxamide of clinical interest, against cloned fresh human tumors.  相似文献   
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OBJECTIVES: This study assessed the influence of public policies on the immunization status of 2-year old children in the United States. METHODS: Up-to-dateness for the primary immunization series was assessed in a national sample of 8100 children from the 1988 National Maternal and Infant Health Survey and its 1991 Longitudinal Follow-Up. RESULTS: Documented immunization rates of this sample were 33% for poor children and 44% for others. More widespread Medicated coverage was associated with greater likelihood of up-to-dateness among poor children. Up-to-dateness was more likely for poor children with public rather than private sources of routine pediatric care, but all children living in states where most immunizations were delivered in the public sector were less likely to be up to date. Poor children in state with partial vaccine replacement programs were less likely to be up to date than those in free-market purchase states. CONCLUSIONS: While state policies can enhance immunization delivery for poor children, heavy reliance on public sector immunization does not ensure timely receipt of vaccines. Public- and private-sector collaboration is necessary to protect children from vaccine-preventable diseases.  相似文献   
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PURPOSE: Arteriography is the diagnostic test of choice before lower extremity revascularization, because it is a means of pinpointing stenotic or occluded arteries and defining optimal sites for the origin and termination of bypass grafts. We evaluated whether a duplex ultrasound scan, used as an alternative to arteriography, could be used as a means of accurately predicting the proximal and distal anastomotic sites in patients requiring peripheral bypass grafts and, therefore, replace standard preoperative arteriography. METHODS: Forty-one patients who required infrainguinal bypass grafts underwent preoperative duplex arterial mapping (DAM). Based on these studies, an observer blinded to the operation performed predicted what operation the patient required and the best site for the proximal and distal anastomoses. These predictions were compared with the actual anastomotic sites chosen by the surgeon. RESULTS: Whether a femoropopliteal or an infrapopliteal bypass graft was required was predicted correctly by means of DAM in 37 patients (90%). In addition, both anastomotic sites in 18 of 20 patients (90%) who had femoropopliteal bypass grafts and 5 of 21 patients (24%) who had infrapopliteal procedures were correctly predicted by means of DAM. CONCLUSION: DAM is a reliable means of predicting whether patients will require femoropopliteal or infrapopliteal bypass grafts, and, when a patient requires a femoropopliteal bypass graft, the actual location of both anastomoses can also be accurately predicted. Therefore, DAM appears able to replace conventional preoperative arteriography in most patients found to require femoropopliteal reconstruction. Patients who are predicted by means of DAM to require crural or pedal bypass grafts should still undergo preoperative contrast studies to confirm these results and to more precisely locate the anastomotic sites.  相似文献   
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