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A plethora of 6-(hetero)aryl C-C and C-N bonded tacrine analogues has been made accessible by employing palladium mediated (Suzuki-Miyaura, Heck, Sonogashira, Stille and Buchwald) cross-coupling reactions, starting from either halogenated or borylated residues. The successful use of Pd(dppf)Cl

A plethora of 6-(hetero)aryl C-C and C-N bonded tacrine analogues has been made accessible by employing palladium mediated (Suzuki-Miyaura, Heck, Sonogashira, Stille and Buchwald) cross-coupling reactions, starting from either halogenated or borylated residues. The successful use of Pd(dppf)Cl2·CH2Cl2 as a common catalytic system in realizing all these otherwise challenging transformations is the highlight of our optimized protocols. The analogues thus synthesized allow the available chemical space around the C-6 of this biologically relevant tacrine core to be explored. The in silico docking studies of the synthesized compounds were carried out against the acetylcholinesterase (AChE) enzyme. The hepatotoxicity studies of these compounds were done against complexes of CYP1A2 and CYP3A4 proteins with known inhibitors like 7,8-benzoflavone and ketoconazole, respectively. © 2022 The Royal Society of Chemistry. Erwin Schrödinger International Institute for Mathematics and Physics, ESI; Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-777; Russian Science Foundation, RSF: 20-73-10205; Council on grants of the President of the Russian Federation: 21-13-00304, 22-23-20189, NSh-1223.2022.1.3 Aravinda Babu is thankful to Syngene International Ltd. for providing the No Objection Certificate (NOC) to pursue his doctoral work. The authors are thankful to Sri Siddhartha Academy of Higher Education and Karnataka Council for Technological Upgradation (KCTU) for rendering all the facilities to carry out the research work. Grigory V. Zyryanov is thankful to Ministry of Science and Higher Education of the Russian Federation (Grant # 075-15-2020-777) for the financial support. Sougata Santra is thankful to Russian Science Foundation (Grant # 20-73-10205) and Grants Council of the President of the Russian Federation (# NSh-1223.2022.1.3). Muthipeedika Nibin Joy is thankful to Russian Science Foundation (Grants ## 22-23-20189 and 21-13-00304). The detailed experimental procedure and characterization data including spectra are available in the ESI uploaded along with the manuscript.

Despite many studies attributing HPV infection to oropharyngeal tumorigenesis, its involvement in non-oropharyngeal cancers is ambiguous. We have evaluated the mutation profile of p16 along with protein expression and correlated it with the HPV status in oral cancers.Somatic mutations in p16 were studied by exome sequencing (n=25) and validated by Sequenom Mass spectrometry (n=50). Expression of p16 was studied by immunohistochemistry (IHC) and correlated with HPV16/18 status evaluated by PCR, and IHC (n=221) in oral cancers.Out of 25 oral cancer patients' samples sequenced by Exome sequencing, p16 mutations were found in 4 samples (16%). All the p16 mutations were identified in patients with cancers in the site of gingivobuccal complex and not tongue subsite. All the 4 patients with p16 mutations had failed treatment, and showed a significantly poor disease-free survival. Insilico analysis of the types of p16 mutations showed mutated, truncated p16 protein having an increased intrinsic disorder, and all the mutations involved truncation post arginine. Validation of the p16 mutations by mass spectrometry showed 8/50 (16%) of patients harbouring pArg80Ter mutation, of which 7/8 (87.5%) had failed treatment. Overexpression of p16 in70% of the tumour cells was found in 21.4% (26/121) OSCC patients, 6.75% (5/74) OPML patients and p16 expression was significantly correlated (p=0.001; χ2 = 25.601) to the grade. All the samples were studied for HPV presence by PCR and IHC. We found that none of the p16 positive tumours showing expression in70% of the tumour cells harbored HPV both by PCR as well as IHC.Our study emphasises the importance of p16 in oral cancers, and shows that oral cancer is not HPV associated and p16 expression is not a surrogate marker for HPV.

Multiple Input Multiple Output Orthogonal Frequency Division Multiplexing (MIMO OFDM) wireless communication is well known in the literature. However, the problems occur in classical MIMO system can be overcome with large number of array antennas such systems, termed as Massive MIMO. But, the latency may be more for these systems using traditional equalizers such as Zero Forcing (ZF) and Minimum Mean Square Error (MMSE). Hence, this paper proposes LDPC coded Massive MIMO OFDM system using Approximate Message Passing (AMP) equalizer. The performance of the proposed system is analysed through simulations. In this simulation, different transmit and receive antennas (64,128), (64,256), (64,512) and (64, 1024) and 16QAM are used. Finally, the performance of LDPC coded and uncoded massive MIMO OFDM using AMP equalizer is analyzed in comparison with ZF and MMSE equalizers using BER and latency as performance measures.

Disk drive technologies have evolved rapidly over the last decade to address the needs of big data. Due to rapid growth in social media, data availability and data protection has become an essence. The availability or protection of the data ideally depends on the reliability of the disk drive. The disk drive speed and performance with minimum cost still plays a vital role as compared to other faster storage devices such as NVRAM, SSD and so forth in the current data storage industry. The disk drive performance model plays a critical role to size the application, to cater the performance based on the business needs. The proposed performance model of disk drives predict how well any application will perform on the selected disk drive based on performance indices such as response time, MBPS, IOPS etc., when the disk performs intended workload.

Objective: To evaluate the clinical tolerability and efficacy of trovafloxacin compared with sparfloxacin in the treatment of lower respiratory tract infections. Design: This was a randomised, double-blind, controlled, parallel study. Participants and Interventions: 92 patients with lower respiratory tract infection were enrolled in three centres. 45 patients received trovafloxacin 200mg once daily orally for 10 days and 43 patients received sparfloxacin 400mg on the first day and 200mg once daily orally for 9 days. Clinical evaluation was performed for fever, dyspnoea, pulmonary symptoms, cough and sputum on days 1, 3, 6 and 12 of the study along with bacteriological evaluation on days 1 and 12. Any adverse effects were also recorded during the study period. Results: There was a significant reduction in the severity of symptoms from day 4 until the end of the study. Clinical cure or improvement was seen in 87 and 95% of the trovafloxacin and sparfloxacin groups, respectively. Bacteriological eradication rates were 84 and 89% for the trovafloxacin and sparfloxacin groups, respectively. The number of adverse effects was 10 and 13 reported by 10 and 13 patients in the trovafloxacin and sparfloxacin groups, respectively. Conclusions: Trovafloxacin is well tolerated and effective in the treatment of lower respiratory tract infections in a dosage of 200mg daily. It was observed that the efficacy and tolerability of trovafloxacin is comparable to that of sparfloxacin (200mg daily, with a loading dose of 400mg on the first day) in the treatment of lower respiratory tract infections. However, further studies are needed to confirm this.

In vitro effect of an Indian variety of chrysotile asbestos from Andhra Pradesh (AP-I) is evaluated using sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. Cultures were treated for 24 hr with different concentrations of asbestos fibers, i.e., 0.1, 1, 10, and 100 μg/ml of medium. Sister chromatid exchanges were elevated even with the lowest concentration used. However, the linear relationship between SCEs and asbestos concentration is not seen.

The effects in vivo and in vitro of benthiocarb, an organocarbamate, on acetylcholinesterase (AChE) activity and its recovery in vitro in the brain of the freshwater fish Sarotherodon mossambicus have been studied. Findings revealed that the specific activity of AChE was inhibited both in vivo and in vitro in a concentration-dependent manner. Of the different modulators tested, dexamethasone (0.72 mg), prednisolone (0.74 mg), testosterone (0.9 mg), and ADP (9.5 mg) were found to neutralize the inhibitory effect (IC50 = 0.30 μM) of benthiocarb on AChE.

Mice were exposed to hexachlorocyclohexane (BHC) in order to study the changes in the serum protein pattern and in the LDH isoenzymes of the liver. After 2 months of exposure the protein pattern showed a new band which persisted even after the development of a tumour. The LDH isoenzymes pattern showed a gradual decrease of the faster moving LDH-1 and LDH-2 bands which later disappeared completely when hepatic tumours formed. The significance of these results is discussed.

Male Swiss mice, 6–8 weeks old, were given a diet containing technical-grade hexachlorocyclohexane (BHC) at 500 ppm continuously for 4,6 and 8 months. After the completion of the scheduled exposure period, the males were sequentially mated with 2–3 untreated virgin females at weekly intervals for 8 weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant-lethal mutation. The number of dead implants, including deciduomas and dead embryos, showed a significant increase. Similarly, the percentage fertility and live embryos per female showed a decline when compared with the control.