Quantification and characterization of uncertainty in metabolic engineering

One of the central problems in metabolic engineering deals with the identification of the "rate limiting steps", i.e. enzymes whose activities one should manipulate towards the achievement of a desirable performance. However, uncertainty about the kinetic characteristics of the enzymes involved in the pathway of interest makes such identification almost impossible. On the other hand, extensive research within metabolic engineering has enabled the estn. of intracellular metabolic fluxes. Such information, while it provides significant understanding about the functioning of metabolic pathways and, some times, guidance for metabolic engineering, it does not allow a quant. prediction of the metabolic pathway responses to metabolic engineering actions, such as changes in enzyme activities. We have recently developed a method that overcomes these limitations and allows the identification of metabolic engineering targets for the manipulation of metabolic pathways based on information about the stoichiometry of the pathways and the assocd. values of the metabolic fluxes. The framework employs knowledge about the stoichiometry of biochem. networks and the estd. values of the assocd. metabolic fluxes, modeling concepts from metabolic control anal., computational methods, and nonparametric statistics. We will present and discuss the application of the method to the central carbon pathways in E. coli and S. cerevisiae for the identification of the metabolic engineering strategies (i.e., changes in enzyme activities) with the highest probability of success in optimizing conversion of glucose to ethanol. [on SciFinder (R)

Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors.

BackgroundThe risks of both endometrial cancer and postmenopausal breast cancer are increased by obesity and higher endogenous estrogen levels. Although aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer is uncertain.MethodsThe authors investigated this issue in a cohort of 17,064 women who were diagnosed with hormone receptor-positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities, and the receipt of adjuvant endocrine therapy was available from electronic medical records and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan's Surveillance, Epidemiology, and End Results-affiliated tumor registry, and rates were compared across endocrine therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers: both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional-hazards models.ResultsEndometrial cancer incidence was a statistically significant 48% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.52; 95% confidence interval, 0.31-0.87; P = .01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37-1.35; P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.67; 95% confidence interval, 0.42-1.06; P = .08), but neither difference was statistically significant. Associations were stronger among those with good drug adherence.ConclusionsIn a community-based, integrated health plan setting, endometrial cancer incidence was lower in women who were receiving an aromatase inhibitor compared with those who were receiving tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen-associated endometrial cancer. Although there were somewhat fewer endometrial cancers in the aromatase inhibitor group versus the no endocrine therapy group, further studies are needed for the definitive assessment of this potential association

Aromatase Inhibitors, Tamoxifen, and Endometrial Cancer in Breast Cancer Survivors

BackgroundBoth endometrial cancer and postmenopausal breast cancer risk are increased by obesity and higher endogenous estrogen levels. While aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer risk is uncertain. Methods We addressed this issue in a cohort of 17,064 women diagnosed with hormone receptor positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities and adjuvant endocrine therapy use was available from electronic medical and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan’s SEER-affiliated tumor registry and rates were compared across endocrine therapy groups(aromatase inhibitor [n=5,303], tamoxifen [n=5155] , switchers [both n=3787] or none [n=2819]using multi-variable adjusted Cox proportional hazard models. Results Endometrial cancer incidence was a statistically significant, 48% lower in the aromatase inhibitor versus tamoxifen group (HR 0.52, 95% CI 0.31-0.87, P=0.01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor versus no endocrine therapy group (HR 0.71, 95% CI 0.37-1.35, P=0.30) and was 36% higher in the tamoxifen versus no endocrinetherapy group (HR 1.36, 95% CI 0.84-2.22, P=0.22), but neither difference was statisticallysignificant. Associations were stronger among those with good drug adherence. Conclusions In a real world experience, endometrial cancer incidence was lower in women on aromatase inhibitor compared to tamoxifen. Additionally, aromatase inhibitors may mitigate tamoxifen-associated endometrial cancer incidence. While there were somewhat fewer endometrial cancers diagnosed in aromatase inhibitor versus no endocrine therapy users, further studies areneeded for definitive assessment of aromatase inhibitor endometrial cancer influence

Maximum Efficiency Per Ampere Control of Synchronous Reluctance Motor Sensorless Drives

The maximum efficiency per ampere (MEPA) control strategy stands out as a highly effective means of improving the efficiency of a synchronous reluctance motor (SynRM) drive. This paper introduces an improved approach to optimizing efficiency that treats the motor and inverter as a unified system, ensuring maximum efficiency throughout operation. Diverging from conventional id=iq or maximum torque per ampere control methods, this approach accounts for both iron losses and inverter losses, while also addressing cross-coupling effects. This is achieved through real-time virtual signal injection, which extracts optimal operation points, and an accurate analytical approach to assess iron losses. Experimental results convincingly validate the effectiveness of this novel methodology

Women committed to the Massachusetts Department of Correction, 1970 to 1980

Comparison of robust Poisson and log-binomial models in estimating risk ratio (RR) of ≥ 7 SABA canisters dispensed in the past year. (DOCX 12 kb

Aromatase Inhibitors, Tamoxifen, and Endometrial Cancer in Breast Cancer Survivors

BackgroundBoth endometrial cancer and postmenopausal breast cancer risk are increased by obesity and higher endogenous estrogen levels. While aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer risk is uncertain. Methods We addressed this issue in a cohort of 17,064 women diagnosed with hormone receptor positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities and adjuvant endocrine therapy use was available from electronic medical and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan’s SEER-affiliated tumor registry and rates were compared across endocrine therapy groups(aromatase inhibitor [n=5,303], tamoxifen [n=5155] , switchers [both n=3787] or none [n=2819]using multi-variable adjusted Cox proportional hazard models. Results Endometrial cancer incidence was a statistically significant, 48% lower in the aromatase inhibitor versus tamoxifen group (HR 0.52, 95% CI 0.31-0.87, P=0.01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor versus no endocrine therapy group (HR 0.71, 95% CI 0.37-1.35, P=0.30) and was 36% higher in the tamoxifen versus no endocrinetherapy group (HR 1.36, 95% CI 0.84-2.22, P=0.22), but neither difference was statisticallysignificant. Associations were stronger among those with good drug adherence. Conclusions In a real world experience, endometrial cancer incidence was lower in women on aromatase inhibitor compared to tamoxifen. Additionally, aromatase inhibitors may mitigate tamoxifen-associated endometrial cancer incidence. While there were somewhat fewer endometrial cancers diagnosed in aromatase inhibitor versus no endocrine therapy users, further studies areneeded for definitive assessment of aromatase inhibitor endometrial cancer influence