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Inherited mutations in BRCA1, BRCA2, and PALB2 cause a high risk of breast cancer. Here, we conducted parallel conditional knockout (CKO) of Brca1, Palb2, and Brca2, individually and in combination, along with one copy of Trp53, in the mammary gland of nulliparous female mice. We observed a functional equivalence of the three genes in their basic tumor-suppressive activity, a linear epistasis of Palb2 and Brca2, but complementary roles of Brca1 and Palb2 in mammary tumor suppression, as combined ablation of either Palb2 or Brca2 with Brca1 led to delayed tumor formation. Whole-exome sequencing (WES) revealed both similarities and differences between Brca1 and Palb2 or Brca2 null tumors. Analyses of mouse mammary glands and cultured human cells showed that combined loss of BRCA1 and PALB2 led to high levels of reactive oxygen species (ROS) and increased apoptosis, implicating oxidative stress in the delayed tumor development in Brca1;Palb2 double CKO mice. The functional complementarity between BRCA1 and PALB2/BRCA2 and the role of ROS in tumorigenesis require further investigation.

Purpose Although the effective and safe medical defoamers, dimethicone (DM) and simethicone (SM) are widely used in electronic gastroscope examination (EGE), their preparations are presented in the form of suspensions or emulsions, these are untransparent or milk-like in appearance and can easily cause misdiagnosis as a result of an unclear field of vision if the doctor does not master the amount of defoamer or operates incorrectly. At the same time, it is also difficult to wash out the camera and pipeline, due to the large oil droplets of preparations. The purpose of this study was to develop a new clear and transparent oil in water (O/W) DM nanoemulsions (DMNs) and observe the effect of application in EGE. Methods The oil phase was chosen for its antifoaming activity and viscosity. The emulsifier and co-emulsifier were selected according to the solubility of the oil phase in them. The water titration method was used to make the pseudoternary phase diagrams of nanoemulsions and optimize the prescription composition. DM-in-water nanoemulsion was prepared by the low energy method and evaluated for appearance, antifoaming ability, droplet size, and stability. The effect of DMNs utilized in EGEs was also observed. Results The optimal formulation of DMNs contained CRH-40 as an emulsifier, PEG-400 as a co-emulsifier, DM as oil phase with the viscosity of 10 mPa.s, and their proportion was 4.5:4.5:1, respectively. DMNs obtained the average particle size of 67.98 nm with the polydispersity index (PDI) of 0.332, and 57.14% defoaming rate. The result of using an EGE showed that DMNs were superior in comparison to the emulsions with regard to the defoaming effect, visual clarity, and easy cleanup. Conclusion DMNs were found to provide excellent visual clarity to its other preparations. The novel DMNs is a promising substitute for DM emulsions or suspensions in EGEs.

The economic production quantity (EPQ) and the economic order quantity (EOQ) models have been widely used in inventory management for vendors and retailers, respectively. However, an optimal solution for the EPQ or the EOQ model is only based on either vendors’ or buyers’ viewpoint. That is, such an optimal solution is usually beneficial to one of the vendors and buyers, but detrimental to the others. Hence, to establish a long-term cooperative relationship between the vendor and buyer, an integrated inventory model is needed. The purpose of this paper is to investigate a single-vendor single-retailer production-inventory model for products with imperfect quality. It is assumed that a 100% inspection process is conducted to screen out the defectives contained in the received lot and the defectives screened out during the 100% inspection process will be returned to the vendor immediately. By maximizing the expected annual integrated total profit, the optimal number of shipments in a cycle and the optimal s...

Background: Countries with limited resources in economic downturns often reduce government expenditures, of which spending on preventive healthcare with no apparent immediate health impact might be cut down first. This research aims to find the optimum share of preventive health expenditure to gross domestic product (GDP) and investigate the implications of preventive health services on economic performance and the population's wellbeing. Methods: We develop the economic growth model to undertake health-economic analyses and parameterize for Taiwan setting. Based on the US experiences over the period from 1975 to 2013, this research further examines the model's predictions on the relationship between preventive health expenditure and economic performance. Results: Theoretical analysis and numerical simulations show that an inverse U-shaped relationship exists between the proportion of GDP spent on prevention and social welfare, as well as between the proportion spent on prevention and economic growth. Empirical analysis shows an under-investment in prevention in Taiwan. The spending of preventive healthcare in Taiwan government was 0.0027 GDP in 2014, while the optimization levels for economic development and social welfare would be 0 · 0119 and 0 · 0203, respectively. There is a statistically significant nonlinear relationship between health expenditure on prevention and the estimated real impact of economic performance from US experiences. The welfare-maximizing proportion of preventive expenditure is usually greater than the proportion maximizing economic growth, indicating a conflict between economic growth and welfare after a marginal share. Conclusion: Our findings indicate that it is worthwhile increasing investment on prevention up until an optimization level for economic development and social welfare. Such levels could also be estimated in other economies.

Techniques that can effectively reduce failure rate, control life span and predict product life are highly expected in modern electronic products. Design for Reliability (DFR) technique introduced in this study, applies various robust design and system reliability modeling methods to evaluate whether reliability target can be met in product development stage. However, DFR technique often faces challenges mainly on insufficient accuracy of system reliability prediction. Prognostics and Health Management (PHM) technique applies failure precursors and their impact on product real failure to improve accuracy of reliability prediction in design phase. This study integrates DFR and PHM techniques for reliability prediction. Hard disk drive is selected as a case study for PHM application in design phase. A failure precursor of drive is selected and its statistical distribution of time-to-failure-precursor is established. Applying conditional reliability and residual mean-time-to-failure, remaining useful life (RUL) estimation is proposed. The prognostic based DFR developed in this study plays a key role in predicting product reliability during development stage as well as catastrophic failure prevention in maintenance stage.