Development of a software tool for reliability estimation

This thesis presents Version 2.0 of Software Tool for Reliability Estimation (STORE 2.0). It expands on the work done by Parekh [1] by revising the algorithm for tie-set and cut-set calculation, by including fault tree reliability analysis, by analyzing state dependent system, and by integrating component and system reliability analysis.;This thesis also presents an approach to the simplification of complex systems by collapsing series and parallel components into a sub-system. The approach was illustrated on an example described by Nelson et al. [2]. The example had 16 components resulting in ten cut-sets and fifty five tie-sets. Upon simplification, the problem was reduced to one tie-set only.;STORE 2.0 integrates parameter estimation, component reliability analysis, system reliability analysis, estimation of reliability of state dependent systems, and fault tree analysis. It was verified and validated on several examples taken from the open literature. The software was developed in Visual Basic 2008 with SQL as the database

A Tabu Search Heuristic for a Generalized Quadratic Assignment Problem

The generalized quadratic assignment problem (GQAP) is the task of assigning a set of facilities to a set of locations such that the sum of the assignment and transportation costs is minimized. The facilities may have different space requirements, and the locations may have varying space capacities. Also, multiple facilities may be assigned to each location such that space capacity is not exceeded. In this paper, an application of the GQAP is presented for assigning a set of machines to a set of locations on the plant floor. Construction algorithms and a simple tabu search heuristic are developed for the GQAP. A set of test problems available in the literature was used to evaluate the performances of the TS heuristic using different construction algorithms. The results show that the simple TS heuristic is effective for solving the GQAP

Total synthesis of (–)-irciniastatin B; Design and synthesis of analogues

The dissertation herein presents the first total synthesis of (-)-irciniastatin B in conjunction with the design and synthesis of analogues. Chapter One details the isolation and biological data of two potent cytotoxins (+)-irciniastatin A and (−)-irciniastatin B by Pettit and Crews. Also outlined in Chapter One are selected total syntheses and endgame strategies for (+)-irciniastatin A and reported structure activity relationship studies of the irciniastatin family of natural products. The synthetic strategy toward the construction of (-)-irciniastatin B is outlined in Chapter Two. A chemoselective deprotection/oxidation sequence was proposed to install the requisite oxidation state at C(11). To this end, a late-stage alcohol from the earlier Smith synthesis of (+)-irciniastatin A was employed. However, protection of the late-stage alcohol as an orthogonal SEM ether resulted in unexpected degradation. A modified protecting group strategy employing robust 3,4-dimethoxybenzyl ethers successfully led to the first total synthesis of (−)-irciniastatin B. This strategy also led to the construction of (+)-irciniastatin A from (-)-irciniastatin B, confirming the structural relationship of these two secondary metabolites. The design and synthesis of irciniastatin analogues are detailed in Chapter Three. Our synthetic strategy permits modification at C(11), which has been suggested to be a key structural element for the potent biological activity observed with the irciniastatins. Biological evaluation of C(11)-irciniastatin analogues will aid in the elucidation of the biological mode of action of the irciniastatin family of natural products

Total Synthesis of (−)-Irciniastatin B and Structural Confirmation via Chemical Conversion to (+)-Irciniastatin A (Psymberin)

The total synthesis and structural confirmation of the marine sponge cytotoxin (−)-irciniastatin B has been achieved via a unified strategy employing a late-stage, selective deprotection/oxidation sequence that provides access to both (+)-irciniastatin A (psymberin) and (−)-irciniastatin B

Cost-Utility Analyses of Diagnostic Laboratory Tests: A Systematic Review

AbstractObjectiveTo review and evaluate the literature of cost-utility analyses (CUAs) regarding diagnostic laboratory testing.MethodsWe reviewed all articles related to diagnostic laboratory testing in the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), which contains detailed information on over 2000 published CUAs through 2008. We analyzed the extent to which the studies adhered to recommended practices for conducting and reporting cost-effectiveness analyses. We also recorded whether the studies contained information on diagnostic test accuracy and costs, and whether any account was taken of potential benefits or harms of testing that are unrelated to subsequent treatment, such as the reassurance value of testing.ResultsWe identified 141 published CUAs pertaining to diagnostic laboratory testing published through 2008 which contained 433 separate incremental cost-effectiveness ratios. Prior to 2000, there were only 20 CUAs published, but the number averaged 13.4 annually thereafter. Most studies focused on hematology/oncology (n = 42, 30%) and obstetrics/gynecology (n = 36, 26%) applications. Approximately 63% (n = 89) of studies clearly reported information about the accuracy of the test, but only 10% (n = 14) mentioned test safety or possible risks. A small number (n = 10, 7%) mentioned or considered the potential value or harm of testing unrelated to treatment consequences. Over 55% of the reported incremental cost-effectiveness ratios (ICERs) were either dominant (more quality-adjusted life years for less cost), or below $50,000 per quality-adjusted life years gained (in 2008 US dollars).ConclusionThe number of CUAs investigating laboratory diagnostic testing has increased substantially with applications to diverse clinical areas. The literature reveals many areas in which testing represents good value for money. The vast majority of studies have not considered preferences for test information unrelated to treatment consequences

Reprogramming the specificity of sortase enzymes

Staphylococcusaureus sortase A catalyzes the transpeptidation of an LPXTG peptide acceptor and a glycine-linked peptide donor and has proven to be a powerful tool for site-specific protein modification. The substrate specificity of sortase A is stringent, limiting its broader utility. Here we report the laboratory evolution of two orthogonal sortase A variants that recognize each of two altered substrates, LAXTG and LPXSG, with high activity and specificity. Following nine rounds of yeast display screening integrated with negative selection, the evolved sortases exhibit specificity changes of up to 51,000-fold, relative to the starting sortase without substantial loss of catalytic activity, and with up to 24-fold specificity for their target substrates, relative to their next most active peptide substrate. The specificities of these altered sortases are sufficiently orthogonal to enable the simultaneous conjugation of multiple peptide substrates to their respective targets in a single solution. We demonstrated the utility of these evolved sortases by using them to effect the site-specific modification of endogenous fetuin A in human plasma, the synthesis of tandem fluorophore –protein–PEG conjugates for two therapeutically relevant fibroblast growth factor proteins (FGF1 and FGF2), and the orthogonal conjugation of fluorescent peptides onto surfaces.Chemistry and Chemical Biolog

Experimental Study and Numerical Simulation of an Electrical Preheating for SAGD Wells in Heavy Oil Reservoirs

It is necessary to establish effective communication between two horizontal wells during the preheating period of steam-assisted gravity-drainage (SAGD). However, the preheating time is usually very long, which results in high steam consumption and CO2 emissions. There is little research on the effects of different wellbore fluids during the preheating period. The heat transfer and heating characteristics of different wellbore fluids–water, heat-conduction oil, and air–were explored by using physical experiments and numerical simulations. In this study, the results indicated that the heat-transfer performance of heat-conduction oil is the best. The numerical simulation’s results indicated that compared with the wellbore saturated with water, the heat-conduction oil reduced the viscosity of crude oil, and energy consumption was not obvious during the preheating stage. The super-heavy oil flowed into the wellbore due to the solubility of the heat-conduction oil and its own gravity. As a result, the super-heavy oil content in the wellbore gradually accumulated, increasing the risk of coking. Those experiments showed that the use of electrical heating provides good potential to improve SAGD efficiency during the preheating period, and water is the best injection fluid for wellbores during the electrical heating process