2,756 research outputs found
Fundamental Properties of Integrated-Depth Equations for Nonlinear Water Propagation in Porous Media
Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv
A Global Method for a Two-Dimensional Cutting Stock Problem in the Manufacturing Industry
A two-dimensional cutting stock problem (2DCSP) needs to cut a set of given rectangular items from standard-sized rectangular materials with the objective of minimizing the number of materials used. This problem frequently arises in different manufacturing industries such as glass, wood, paper, plastic, etc. However, the current literatures lack a deterministic method for solving the 2DCSP. However, this study proposes a global method to solve the 2DCSP. It aims to reduce the number of binary variables for the proposed model to speed up the solving time and obtain the optimal solution. Our experiments demonstrate that the proposed method is superior to current reference methods for solving the 2DCSP
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FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.
BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)
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