Single Machine Scheduling to Maximize Number of Batch of Jobs with Uncertain Processing Times

The paper studies single-machine scheduling to maximize number of batch of jobs with uncertain processing times. Firstly, an expected value model to maximize number of batch of jobs processed is given based on uncertainty theory. Then, the model is transformed into a deterministic integer programming model and its properties are provided. Further, its arithmetic, called Man-computer Alternant Arithmetic, is presented. Finally, a numerical example on the model is given

Generation of Sst-P2a-Mcherry Reporter Human Embryonic Stem Cell Line Using the Crispr/cas9 System (WAe001-A-2C)

Somatostatin (SST)-producing pancreatic delta-cells play an important role in maintaining the balance of insulin and glucagon secretion within the islets. This study aimed to generate a human embryonic stem cell (hESC) line with a SST-P2A-mCherry reporter using CRISPR/Cas9 system. The SST-P2A-mCherry reporter cell line was shown to maintain typical pluripotent characteristics and able to be induced into SST-producing pancreatic delta-cells. The generation of the cell line would provide useful platform for the characterization of stem cell-derived delta-cells, discovery of delta-cell surface markers and investigation of paracrine mechanisms, which will ultimately promote the drug discovery and cell therapy of diabetes mellitus

MLN4924 (Pevonedistat), a protein neddylation inhibitor, suppresses proliferation and migration of human clear cell renal cell carcinoma

Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC). Levels of both Nedd8 activating enzyme E1 and Nedd8- conjugating enzyme E2 were higher in ccRCC tissues and RCC cancer cells than in normal. Moreover, MLN4924 treatment led to rapid inhibition of Cullin1 neddylation and notably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies revealed that MLN4924 induced the accumulation of a number of CRL substrates, including p21, p27 and Wee1 to trigger DNA damage and induce growth arrest at the G2/M phase. MLN4924 also induced antimigration and anti-invasion by activating E-cadherin and repressing Vimentin. Taken together, this study provides the first evidence that neddylation pathway is overactive in ccRCC and that MLN4924 induces dose-dependent anti-proliferation, anti-migration, anti-invasion in ccRCC cells. The study thus indicates that MLN4924 has potential therapeutic value for the clinical treatment of renal cance

USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency

The homeobox transcription factor Nanog has a vital role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). Stabilization of Nanog proteins is essential for ESCs. The ubiquitin–proteasome pathway mediated by E3 ubiquitin ligases and deubiquitylases is one of the key ways to regulate protein levels and functions. Although ubiquitylation of Nanog catalyzed by the ligase FBXW8 has been demonstrated, the deubiquitylase that maintains the protein levels of Nanog in ESCs yet to be defined. In this study, we identify the ubiquitin-specific peptidase 21 (USP21) as a deubiquitylase for Nanog, but not for Oct4 or Sox2. USP21 interacts with Nanog protein in ESCs in vivo and in vitro. The C-terminal USP domain of USP21 and the C-domain of Nanog are responsible for this interaction. USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog, stabilizing Nanog. USP21-mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs. Depletion of USP21 in mouse ESCs leads to Nanog degradation and ESC differentiation. Overall, our results demonstrate that USP21 maintains the stemness of mouse ESCs through deubiquitylating and stabilizing Nanog

Establishment of a subcutaneous xenograft tumor model of alveolar echinococcosis in nude mice

ObjectiveTo establish a subcutaneous xenograft tumor model of alveolar echinococcosis in nude mice, and to lay a foundation for further research on alveolar echinococcosis. MethodsA total of 25 nude mice were given subcutaneous injection of 0.1 ml 20% Echinococcus multilocularis protoscolex suspension at the back of the neck. The growth of lesions was observed and recorded, and trypan blue staining was performed at 6 months after injection to observe the cell viability of protoscolices. ResultsSubcutaneous lesions were observed at about 8 days after injection. At 3 months after the establishment of the model, the survival rate of the nude mice was 92% (23/25), and the infection rate of Echinococcus multilocularis was 100% (23/23). A small number of protoscolices died and were blue on trypan blue staining, and the cell viability of protoscolices was 98%. ConclusionEchinococcus multilocularis can be successfully transplanted to the subcutaneous part of nude mice, which provides a reference for further studies on the establishment of animal models of alveolar echinococcosis