Cancer informatics analysis indicates high CHAC2 associated with unfavorable prognosis in breast cancer.

Breast cancer remains the most commonly diagnosed cancer worldwide and exhibits a poor prognosis. The induction of genetic changes deregulates several genes that increase the disposal towards this life-threatening disease. CHAC2, a member of the glutathione degrading enzyme family has been shown to suppress gastric and colorectal cancer progression, however, the expression of CHAC2 in breast cancer has not been reported. We did an analysis of CHAC2 expression in breast cancer patients from various online tools like UALCAN, GEPIA2, GENT2, TIMER2, and bcGenExminer v4.8. Further, we used the Kaplan-Meier plotter to establish the significance of CHAC2 in BC patient survival and prognosis while TISIDB and TIMER databases were used to investigate the filtration of immune cells. The results showed that CHAC2 levels were high in breast cancer patients and elevated CHAC2 was associated with low overall survival. Taken together, the results of the present study show that like its paralog CHAC1, CHAC2 may also be an important biomarker and could have a potential therapeutic implication in breast cancer.

National Control Laboratory Assessment of Quality of Rituximab Biosimilars in India.

In past few years many rituximab (RTX) biosimilars have been launched in India. Biosimilars are products that are similar in terms of quality, safety, and efficacy to its innovator product and are expected to offer improved affordability. The less clinical examination is a significant source of reduction in the cost of development of a biosimilar. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. Therefore, the role of National Control Laboratory become very important to ensure the quality of these drugs by carrying out analytical characterization at the point of drug product release level as when referred by National Regulatory Authority for quality evaluation. To assess the similarity between innovator and biosimilars, different physicochemical and biological quality attributes were assessed. A multitude of state-of-the-art analysis of N = 3 RTX biosimilars marketed in India revealed that the impurity profiles of these biosimilars measured by charge variant analysis (cation exchange chromatography-high performance liquid chromatography [HPLC], capillary zone electrophoresis, and capillary isoelectric focusing), aggregates profiling (size exclusion chromatography-HPLC), fragments analysis (capillary electrophoresis-sodium dodecyl sulfate) were found to be significantly varying as compared with the innovator product. There were significant variations in acidic variants (p = 0.023) and basic variants (p = 0.0005), isoelectric point value (p < 0.0001), aggregates (p = 0.0231), and fragments (p < 0.0001) of biosimilars were found as that of innovator product. However, these differences were not affecting the biological activity in the cell-based potency analysis by complement-dependent cytotoxicity (CDC) assay (p = 0.1026), antibody-dependent cell-mediated cytotoxicity (ADCC) (p = 0.3736), and binding assay by flow cytometer fluorescence-activated cell sorting (p = 0.4005) of these biosimilars as compared with the innovator product.

Dynamic Energy Management System for a Smart Microgrid.

This paper presents the development of an intelligent dynamic energy management system (I-DEMS) for a smart microgrid. An evolutionary adaptive dynamic programming and reinforcement learning framework is introduced for evolving the I-DEMS online. The I-DEMS is an optimal or near-optimal DEMS capable of performing grid-connected and islanded microgrid operations. The primary sources of energy are sustainable, green, and environmentally friendly renewable energy systems (RESs), e.g., wind and solar; however, these forms of energy are uncertain and nondispatchable. Backup battery energy storage and thermal generation were used to overcome these challenges. Using the I-DEMS to schedule dispatches allowed the RESs and energy storage devices to be utilized to their maximum in order to supply the critical load at all times. Based on the microgrid's system states, the I-DEMS generates energy dispatch control signals, while a forward-looking network evaluates the dispatched control signals over time. Typical results are presented for varying generation and load profiles, and the performance of I-DEMS is compared with that of a decision tree approach-based DEMS (D-DEMS). The robust performance of the I-DEMS was illustrated by examining microgrid operations under different battery energy storage conditions.

Factors modifying transcriptional regulation of signaling genes have putative role in tumor development and progression in humans.

Genes involved in signaling are highly regulated at the level of transcription. Several factors have been known to play role in transcriptional modification of genes. Among these DNA sequence variations present in the regulatory region and aberrant methylation of CpG Iceland in promoter region are the most important factors modifying transcriptional regulation of genes. DNA sequence variation interferes with assembling of regulatory protein TF (transcription factor) on the cis elements TFBS (transcription factor binding site). Presence of variations in regulatory region may alter the level of gene product via interaction of TF to TFBS (transcriptional modification). Promoter hypermethylation causes gene silencing and responsible for transcriptional dysregulation of gene. JAK-1, STAT-3, IL-6, MAPK and AR genes participate in signaling pathway and are tightly regulated. Overexpression of IL-6 and activated STAT3 may contribute to the development of prostate cancer and possibly other human cancers. Indeed, constitutively activated STAT3 have been found in a growing number of human tumors. In the present work, we have predicted 34 regulatory polymorphisms that lies in TFBS of 5 (JAK-1, STAT-3, IL-6, MAPK and AR) signaling genes and compare the methylation of CpG Iceland in promoter region of above motioned genes. On the basis of these predictions, it has been hypothesized that transcriptional modification of gene resulting from the DNA sequence variations in regulatory region or promoter hypermethylation increases the susceptibility to diseases such as cancer by alteration in the level of signaling genes product. Presence of DNA sequence variations may also influence the response to a particular drug.