Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application

Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily. It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs, heavy metal anions, toxicants, and conjugates of glutathione, glucuronide and sulfate. With the advance of sequence technology, many MRP1/ABCC1 polymorphisms have been identified. Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility. In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms. In this review, we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, toxicity, disease susceptibility and severity, prognosis prediction, and methods to select and predict functional polymorphisms

Sequencing geographical data for efficient query processing on air in mobile computing.

Three cost models are derived to measure Data Broadcast Wait (DBW), Data Access Time in the multiplexing scheme (ATDataMul) where both data and indices are broadcast in the same channel, and Data Access Time in the separate channel scheme (ATDataSep) where data and indices are broadcast in two separate channels. Hypergraph representations are used to represent the spatial relationships of both point data and graph data. The broadcast data placement problem is then converted to the graph layout problem. A framework for classifying ordering heuristics for different types of geographical data is presented. A low-polynomial cost approximation graph layout method is used to solve the DBW minimization problem. Based on the proven monotonic relationship between ATData Sep and DBW, the same approximation method is also used for AT DataSep optimization. A novel method is developed to optimize ATDataMul. Experiments using both synthetic and real data are conducted to evaluate the performance of the ordering heuristics and optimization methods. The results show that R-Tree traversal ordering heuristic in conjunction with the optimization methods is effective for sequencing point data for spatial range query processing, while graph partition tree traversal ordering heuristic in conjunction with the optimization methods is suitable for sequencing graph data for network path query processing over air.Geographical data broadcasting is suitable for many large scale dissemination-based applications due to its independence of number of users, and thus it can serve as an important part of intelligent information infrastructures for modern cities. In broadcast systems, query response time is greatly affected by the order in which data items are being broadcast. However, existing broadcast ordering techniques are not suitable for geographical data because of the multi-dimension and rich semantics of geographical data. This research develops cost models and methods for placing geographical data items in a broadcast channel based on their spatial semantics to reduce response time and energy consumption for processing spatial queries on point data and graph data

Enzyme-linked immunospot assay response to recombinant CFP-10/ESAT-6 fusion protein among patients with spinal tuberculosis: implications for diagnosis and monitoring of surgical therapy

SummaryObjectiveThis study aimed to assess the performance of a laboratory-developed recombinant CFP-10/ESAT-6 fusion protein (rCFP-10/ESAT-6)-based enzyme-linked immunospot (ELISPOT) assay for the diagnosis of spinal tuberculosis (TB) in China, and to evaluate the value of the ELISPOT assay for monitoring the efficacy of surgical treatment.MethodsIn the first part of the study, a total of 78 participants were consecutively recruited for ELISPOT using rCFP-10/ESAT-6 as a stimulus. The cutoff value for ELISPOT positivity was based on the results of receiver operating characteristic curve analysis. In the second part, this approach was evaluated in a prospective study including 102 patients with suspected spinal TB. Data on clinical characteristics of the patients and conventional laboratory results were collected, and blood samples were obtained for ELISPOT using rCFP-10/ESAT-6 as a stimulus.ResultsAmong the 102 patients with suspected spinal TB, 11 were excluded from the study. Twenty-three patients (25.2%) had culture-confirmed TB and 29 (31.9%) patients had probable TB. Among the spinal TB patients, the ELISPOT had a sensitivity of 82.7%, compared to a sensitivity of 61.5% for the purified protein derivative (PPD) skin test. The specificity was 87.2% for ELISPOT and 46.2% for the PPD skin test among 39 subjects with non-TB disease. The number of spot-forming cells and/or the positive rate of the ELISPOT assay were associated with aging, emaciation, and paravertebral abscess. The number of subjects with responses to rCFP-10/ESAT-6 slightly decreased after surgical treatment in spinal TB patients.ConclusionsA laboratory-developed rCFP-10/ESAT-6 ELISPOT assay is a useful adjunct to current tests for the diagnosis of spinal TB