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Future Optimization (future + optimization)
Selected AbstractsNumerical simulation of DNA sample preconcentration in microdevice electrophoresisELECTROPHORESIS, Issue 6 2005Alok Srivastava Abstract A numerical model is presented for the accurate and efficient prediction of preconcentration and transport of DNA during sample introduction and injection in microcapillary electrophoresis. The model incorporates conservation laws for the different buffer ions, salt ions, and DNA sample, coupled through a Gaussian electric field to account for the field modifications that cause electromigration. The accuracy and efficiency required to capture the physics associated with such a complex transient problem are realized by the use of the finite element-flux corrected transport (FE-FCT) algorithm in two dimensions. The model has been employed for the prediction of DNA sample preconcentration and transport during electrophoresis in a double-T injector microdevice. To test its validity, the numerical results have been compared with the corresponding experimental data under similar conditions, and excellent agreement has been found. Finally, detailed results from a simulation of DNA sample preconcentration in electrophoretic microdevices are presented using as parameters the electric field strength and the other species concentrations. The effect of the Tris concentration on sample stacking is also investigated. These results demonstrate the great potential offered by the model for future optimization of such microchip devices with respect to significantly enhanced speed and resolution of sample separation. [source] Computerized physician order entry (CPOE) system: expectations and experiences of usersJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 4 2010Jasperien E. Van Doormaal PharmD Abstract Objectives, To explore physicians' and nurses' expectations before and experiences after the implementation of a computerized physician order entry (CPOE) system in order to give suggestions for future optimization of the system as well as the implementation process. Method, On four internal medicine wards of two Dutch hospitals, 18 physicians and 42 nurses were interviewed to measure expectations and experiences with the CPOE system. Using semi-structured questionnaires, expectations and experiences of physicians and nurses with the CPOE system were measured with statements on a 5-point Likert scale (1 = completely disagree, 5 = completely agree). The percentage respondents agreeing (score of 4 or 5) was calculated. Chi-squared tests were used to compare the expectations versus experiences of physicians and nurses and to assess the differences between physicians and nurses. Results, In general, both physicians and nurses were positive about CPOE before and after the implementation of this system. Physicians and nurses did not differ in their views towards CPOE except for the overview of patients' medication use that was not clear according to the nurses. Both professions were satisfied with the implementation process. CPOE could be improved especially with respect to technical aspects (including the medication overview) and decision support on drug,drug interactions. Conclusion, Overall we conclude that physicians and nurses are positive about CPOE and the process of its implementation and do accept these systems. However, these systems should be further improved to fit into clinical practice. [source] Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammationMEDICINAL RESEARCH REVIEWS, Issue 4 2002Ana Martinez Abstract Glycogen synthase kinase 3 (GSK-3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. Two forms of the enzyme, GSK-3, and GSK-3,, have been previously identified. Small molecules inhibitors of GSK-3 may, therefore, have several therapeutic uses, including the treatment of neurodegenerative diseases, diabetes type II, bipolar disorders, stroke, cancer, and chronic inflammatory disease. As there is lot of recent literature dealing with the involvement of GSK-3 in the molecular pathways of different diseases, this review is mainly focused on the new GSK-3 inhibitors discovered or specifically developed for this enzyme, their chemical structure, synthesis, and structure,activity relationships, with the aim to provide some clues for the future optimization of these promising drugs. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 4, 373,384, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10011 [source] In vitro characterization of HCN channel kinetics and frequency dependence in myocytes predicts biological pacemaker functionalityTHE JOURNAL OF PHYSIOLOGY, Issue 7 2009Xin Zhao The pacemaker current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, contributes to the initiation and regulation of cardiac rhythm. Previous experiments creating HCN-based biological pacemakers in vivo found that an engineered HCN2/HCN1 chimeric channel (HCN212) resulted in significantly faster rates than HCN2, interrupted by 1,5 s pauses. To elucidate the mechanisms underlying the differences in HCN212 and HCN2 in vivo functionality as biological pacemakers, we studied newborn rat ventricular myocytes over-expressing either HCN2 or HCN212 channels. The HCN2- and HCN212-over-expressing myocytes manifest similar voltage dependence, current density and sensitivity to saturating cAMP concentrations, but HCN212 has faster activation/deactivation kinetics. Compared with HCN2, myocytes expressing HCN212 exhibit a faster spontaneous rate and greater incidence of irregular rhythms (i.e. periods of rapid spontaneous rate followed by pauses). To explore these rhythm differences further, we imposed consecutive pacing and found that activation kinetics of the two channels are slower at faster pacing frequencies. As a result, time-dependent HCN current flowing during diastole decreases for both constructs during a train of stimuli at a rapid frequency, with the effect more pronounced for HCN2. In addition, the slower deactivation kinetics of HCN2 contributes to more pronounced instantaneous current at a slower frequency. As a result of the frequency dependence of both instantaneous and time-dependent current, HCN2 exhibits more robust negative feedback than HCN212, contributing to the maintenance of a stable pacing rhythm. These results illustrate the benefit of screening HCN constructs in spontaneously active myocyte cultures and may provide the basis for future optimization of HCN-based biological pacemakers. [source] | ||||||||||