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Breast cancer is a heterogeneous disease that comprises multiple histological and molecular subtypes. To gain insight into mutations that drive breast tumorigenesis, we describe a pipeline for the identification and validation of tumor suppressor genes. Based on an in vivo genome‐wide CRISPR/Cas9 screen in Trp53+/– heterozygous mice, we identified tumor suppressor genes that included the scaffold protein Axin1, the protein kinase A regulatory subunit gene Prkar1a, as well as the proof‐of‐concept genes Pten, Nf1, and Trp53 itself. Ex vivo editing of primary mammary epithelial organoids was performed to further interrogate the roles of Axin1 and Prkar1a. Increased proliferation and profound changes in mammary organoid morphology were observed for Axin1/Trp53 and Prkar1a/Trp53 double mutants compared to Pten/Trp53 double mutants. Furthermore, direct in vivo genome editing via intraductal injection of lentiviruses engineered to express dual short‐guide RNAs revealed that mutagenesis of Trp53 and either Prkar1a, Axin1, or Pten markedly accelerated tumor development compared to Trp53‐only mutants. This proof‐of‐principle study highlights the application of in vivo CRISPR/Cas9 editing for uncovering cooperativity between defects in tumor suppressor genes that elicit mammary tumorigenesis. TP53 mutations occur frequently in breast cancer. Here, we describe a framework to identify novel tumor suppressor genes that cooperate with loss of Trp53 in mammary tumorigenesis using an in vivo genome‐wide CRISPR/Cas9 screen. Hits were validated through genetic editing of mammary epithelial organoids in vitro and direct editing of ductal cells in vivo using engineered lentiviruses.

Purpose - The purpose of this paper is to investigate the effects of various dimensions of customer relationship management (CRM) on innovation capabilities. Five dimensions of CRM (information sharing, customer involvement, long-term partnership, joint problem-solving, and technology-based CRM) and five aspects of innovation capability (product, process, administrative, marketing, and service innovations) are identified. The one-to-one associations between the two constructs are developed and verified.Design methodology approach - Data from 107 Taiwanese computer manufacturers are collected. Multiple regression analysis is employed to examine the effects of CRM on innovation capabilities.Findings - The following results are offered: computer manufacturers in Taiwan perform various levels of CRM and, consequently, display different levels of effects on each of the five innovation capabilities. Generally, firms are able to increase their innovation capability by ad hoc CRM; the relationship between customer involvement and process innovation; customer involvement and administrative innovation; and long-term partnership and marketing innovation are not significant; and technology-based CRM has positive effects on all five types of innovation.Practical implications - The findings suggest that not all CRM activities contribute to innovation programs, which clearly indicates the need for applying other mechanisms, such as supplier integration, to form a complete innovation program. Managers should align the development of their supplier management and CRM practices with the desired innovation capability.Originality value - The one-to-one relationships between CRM practices and innovation capabilities have not been properly examined. The findings suggest the need for more research in this area, and the statistical results provide managers with useful guidelines for implementing appropriate CRM practices to develop specific innovation capabilities to respond to enhanced competitiveness.

Purpose – Despite the stimulation provided by market demand and green issues on business performance, the exact nature of the relationships among these aspects remains an issue of contention. This study sought to bridge this gap in the research by examining the effects of market demand on firm performance using green innovation and environmental performance as mediators. The paper aims to discuss these issues. Design/methodology/approach – The Taiwanese hybrid vehicle industry was targeted as the scope of research. Using random sampling method, survey questionnaires were distributed to retailers, wholesalers, and component sale firms in the industry through post and e-mails. AMOS 5.0 and the structural equation modeling (SEM) were used to test the hypotheses and the theoretical model. Findings – Except for the impact of market demand on environmental performance, all relationships were found to be significant. The mediating effect of green innovation which was proven to be significant, while that of environmental performance remained insufficient. Research limitations/implications – This study has a number of limitations. The use of figures from a single industry partly restricts the generalizability of these findings. Practical implications – These results suggest that firms should make greater efforts to understand customer needs and promote core competencies in the innovation of green products and processes to align green initiatives with consumer values in order to satisfy market demand and ensure sustainable performance. Social implications – This study has important implications for the hybrid vehicle industry in particular and all businesses in general. The results provide guidelines for the enhancement of business performance. Based on the significant impact of market demand on green innovation, this study strongly recommends that firms make greater efforts to understand customer needs and expectations. Originality/value – This study was the first to establish a model for investigating the links among market demand, green innovation, environmental performance, and firm performance in the Taiwanese hybrid vehicle industry. The findings provide effective guidelines for the achievement of market leadership and sustainable performance.

Purpose - Entrepreneurial orientation (EO) purportedly enhances a firm's competitive edge, but its alignment with specific dimensions of manufacturing flexibility has not been convincingly documented. The purpose of this study is to investigate the effects of several identifiable aspects of EO on particular types of manufacturing flexibility.Design methodology approach - Using the data collected from 115 motherboard manufacturers, the study employs multiple regression analysis to examine the effects of entrepreneurial practices on manufacturing flexibility.Findings - The statistical results lead to the following conclusions: autonomy, innovativeness, risk-taking and proactiveness have significant positive effects on new product flexibility; autonomy, innovativeness, and competitive aggressiveness improve product mix flexibility; innovativeness, proactiveness, and competitive aggressiveness determine volume flexibility.Research limitations implications - The research focuses exclusively on external manufacturing flexibility, ignoring, for the time being, internal manufacturing flexibility factors.Practical implications - The outcomes of the present study reveal that manufacturing flexibility cannot be achieved by simply installing a computer-aided system; rather, it needs to be planned, managed, and integrated with a firm's entrepreneurial endeavors.Originality value - This is the first empirical study to investigate the effects of EO on manufacturing flexibility rather than on business performance, which most of the previous research on this topic has emphasized. In terms of practical applicability, the findings provide plant managers with valuable guidelines for improving manufacturing flexibility by undertaking appropriate entrepreneurial action.

The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS’ functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent.

This study is to investigate the effect of deep sea water (DSW) on the exercise-induced fatigue of rats. The exhaustive exercise test on the treadmill and the measurement of biochemical values related to fatigue were conducted after the two-week feeding to male Wistar rats with different hardnesses DSW (DRO, D100, D600) in different dosages (6, 12, 30 mL/kg·d). It was found that the exhausting time and the ratio of lactic acid elimination to lactic acid increment from the experiment groups were significantly better than those from the control group. The BUN level of rats fed with D100 in a dosage of 30 mL/kg·d and D600 in three dosages distinctly was lower than that of the control group. The liver glycogen content in the group that the rats fed with D100 in dosages of 6 and 30 mL/kg·d and D600 in a dosage of 30 mL/kg·d showed significant difference compared with control group. However, the weight gain, kidney-body weight ratio, spleen-body weight ratio, and total plasma protein level in the rats of experimental groups showed no significant difference from those of control group. It suggested that endurance, adaptation for exercising load and accelerating elimination in fatigue of rats were improved when fed with higher hardness and dosage of DSW.

In this study, piezoelectric micropumps with partial throw-away design have been developed and discussed. The actuator, a rectangular piezoelectric plate, can be separated from the pump body and be used repeatedly while the pump chamber is single-use to prevent infection. Thus, a low cost and waste solution for biomedical uses is achieved. A mechanical model is used to analyze the behavior of pump diaphragm and chamber geometry. Pump chamber with 20mm diameter is used due to its moderate elasticity. Then, 5 pumps with different depth of pump chamber have been made. The maximum flow rate, 5.7g/min, is reached by using a 0.5mm pump chamber with a 200V actuated voltage.

The objective of this study was to explore the effect of the character of chitosans used, and the regeneration conditions employed on, the yield and physicochemical characteristics of regenerated products. Different concentrations of acetic acid were used to dissolve chitosans of 61.7% and 94.9% degree of deacetylation (DD), and weight-average molecular weight (Mw) of 176 and 97 kDa, respectively; they were then precipitated with an 8 N NaOH solution, followed by washing and neutral and freeze drying to get the regenerated products. Yields of regenerated products and their physicochemical properties, such as ash content, bulk density, Mw, polydispersity index (PDI), DD, and crystallinity were measured. A higher concentration of acetic acid used resulted in a higher yield. The purity of the regenerated product increased significantly, whereas the bulk density and crystallinity decreased significantly after regeneration. The regeneration process showed its merits of narrowing down the PDI of regenerated products. The DD and structure of chitosan was changed insignificantly after the regeneration process.

The objectives of this study are to explore the effect of the ionic strength of aqueous acidic media and the intrinsic characteristics of chitosan used on the formation of different types of aggregation. Two different degrees of acetylation (DA) of β-chitosan are prepared from β-chitin by stepwise alkali deacetylation. These two chitosans have high chain stiffness and typical good solvent behavior in a 0.20 M acetic acid/0.10 M sodium acetate buffer solution. However, a trace amount of aggregates forms in the higher DA chitosan dilute solution. At ionic strength (I) ≥ 0.20 M, the association of compact chitosan forms and/or the amount of the aggregates increases with increasing I of the media. At I = 0.01 M, a considerable quantity of particle structure is observed in the low ionic strength solution and the electrodynamic coupling effect predominates on the mobile behavior of the extended and congested chitosan molecule in solution.