New Emerging SARS-CoV-2 Virus; Structure, Function, and Bioinformatics Analysis

The novel coronavirus, known as a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a single-stranded RNA virus, from which structural and some accessory proteins are encoded. It seems that this newly emerged virus uses the ACE2 receptor to enter the cells in the human body. SARS-CoV-2 undergoes an intense immunological pressure in humans, and this generates mutations to bypass the immune system. Some mutations have been detected in this virus genome, which can induce a change in viral potency. By performing pathway enrichment analysis over those genes and identifying relevant protein-protein interactions (PPIs), we were able to list essential pathways affected in infected cells. In this review, we mainly discuss genetic, intracellular mechanisms, diagnosis and feasible therapeutic targets of this novel coronavirus

A Variable Block Insertion Heuristic for the Blocking Flowshop Scheduling Problem with Total Flowtime Criterion

In this paper, we present a variable block insertion heuristic (VBIH) algorithm to solve the blocking flowshop scheduling problem with the total flowtime criterion. In the VBIH algorithm, we define a minimum and a maximum block size. After constructing the initial sequence, the VBIH algorithm starts with a minimum block size being equal to one. It removes the block from the current sequence and inserts it into the partial sequence sequentially with a predetermined move size. The sequence, which is obtained after several block moves, goes under a variable local search (VLS), which is based on traditional insertion and swap neighborhood structures. If the new sequence obtained after the VLS local search is better than the current sequence, it replaces the current sequence. As long as it improves, it keeps the same block size. However, if it does not improve, the block size is incremented by one and a simulated annealing-type of acceptance criterion is used to accept the current sequence. This process is repeated until the block size reaches at the maximum block size. Furthermore, we present a novel constructive heuristic, which is based on the profile fitting heuristic from the literature. The proposed constructive heuristic is able to further improve the best known solutions for some larger instances in a few seconds. Parameters of the constructive heuristic and the VBIH algorithm are determined through a design of experiment approach. Extensive computational results on the Taillard’s well-known benchmark suite show that the proposed VBIH algorithm outperforms the discrete artificial bee colony algorithm, which is one of the most efficient algorithms recently in the literature. Ultimately, 52 out of the 150 best known solutions are further improved with substantial margins

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer

The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer