Fractionation of antibacterial extracts of Syzygium cumini (Myrtaceae) seeds

Antibacterial activity of Syzygium cumini seed extracts prepared in methanol and ethanol was evaluated by disc diffusion and broth dilution assays. Both extracts exerted a broad spectrum of bacteriostatic action against different gram-positive and gram-negative bacteria. Their minimum inhibitory concentration (MIC) against susceptible organisms ranged from 154-656 μg/mL. Highest total activity was registered by the ethanol extract against Staphylococcus epidermidis. Extracts were separated on TLC (thin-layer chromatography) plates, and separated components were individually tested  for their antibacterial activity. HPLC (high performance liquid chromatography) analysis indicated presence of gallic acid and quercetin in the methanolic extract

Investigation Of High-k Gate Dielectrics And Metals For Mosfet Devices.

Progress in advanced microlithography and deposition techniques have made feasible high- k dielectric materials for MOS transistors. The continued scaling of CMOS devices is pushing the Si-SiO2 to its limit to consider high-k gate dielectrics. The demand for faster, low power, smaller, less expensive devices with good functionality and higher performance increases the demand for high-k dielectric based MOS devices. This thesis gives an in-depth study of threshold voltages of PMOS and NMOS transistors using various high-k dielectric materials like Tantalum pent oxide (Ta2O5), Hafnium oxide (HfO2), Zirconium oxide (ZrO2) and Aluminum oxide (Al2O3) gate oxides. Higher dielectric constant may lead to high oxide capacitance (Cox), which affects the threshold voltage (VT) of the device. The working potential of MOS devices can be increased by high dielectric gate oxide and work function of gate metal which may also influence the threshold voltage (VT). High dielectric materials have low gate leakage current, high breakdown voltage and are thermally stable on Silicon Substrate (Si). Different kinds of deposition techniques for different gate oxides, gate metals and stability over silicon substrates are analyzed theoretically. The impact of the properties of gate oxides such as oxide thickness, interface trap charges, doping concentration on threshold voltage were simulated, plotted and studied. This study involved comparisons of oxides-oxides, metals-metals, and metals-oxides. Gate metals and alloys with work function of less than 5eV would be suitable candidates for aluminum oxide, hafnium oxide etc. based MOSFETs

Protein-Protein Interactions in Malaria: Emerging Arena for Future Chemotherapeutics

Malaria is one of the most deadly diseases infecting humans. Advances in elimination and vector control have reduced the global malaria burden in the past decade; however, the emerging threat of drug resistance and suboptimal vaccine efficacies threaten global eradication efforts. Unlocking novel drug and vaccine targets while simultaneously mitigating spread of resistant strains seems to be the need of the hour. Protein-protein interactions (PPIs), an integral part of host-pathogen cross-talk and parasite survival, have only recently emerged as promising drug targets. Large PPI networks (interactome) are being developed to better our understanding of various parasite biochemical pathways. In this chapter, we throw light on several newly characterized protein-protein interactions between the host (humans) and parasite (plasmodium) in key processes such as hemoglobin degradation, enzyme regulation, protein export, egress, invasion, and drug resistance and further discuss their viability for development as novel chemotherapeutic targets

2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid (Activator-3) is a potent activator of AMPK

AMPK is considered as a potential high value target for metabolic disorders. Here, we present the molecular modeling, in vitro and in vivo characterization of Activator-3, 2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid, an AMP mimetic and a potent pan-AMPK activator. Activator-3 and AMP likely share common activation mode for AMPK activation. Activator-3 enhanced AMPK phosphorylation by upstream kinase LKB1 and protected AMPK complex against dephosphorylation by PP2C. Molecular modeling analyses followed by in vitro mutant AMPK enzyme assays demonstrate that Activator-3 interacts with R70 and R152 of the CBS1 domain on AMPK γ subunit near AMP binding site. Activator-3 and C2, a recently described AMPK mimetic, bind differently in the γ subunit of AMPK. Activator-3 unlike C2 does not show cooperativity of AMPK activity in the presence of physiological concentration of ATP (2 mM). Activator-3 displays good pharmacokinetic profile in rat blood plasma with minimal brain penetration property. Oral treatment of High Sucrose Diet (HSD) fed diabetic rats with 10 mg/kg dose of Activator-3 once in a day for 30 days significantly enhanced glucose utilization, improved lipid profiles and reduced body weight, demonstrating that Activator-3 is a potent AMPK activator that can alleviate the negative metabolic impact of high sucrose diet in rat model

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

In vitro antibacterial activity in seed extracts of Manilkara zapota, Anona squamosa, and Tamarindus indica

Extracts prepared from seeds of Manilkara zapota, Anona squamosa, and Tamarindus indica were screened for their antibacterial activity by disc diffusion and broth dilution methods. Acetone and methanol extracts of T. indica seeds were found active against both gram-positive and gram-negative organisms. MIC values of potent extracts against susceptible organisms ranged from 53-380 &#956;g/mL. Methanol extract of T. indica and acetone extract of M. zapota seeds were found to be bactericidal

Scheduling Spots on Television

The scheduling of advertisements, or spots, is an essential operational process of the television business that must be conducted daily. An efficient distribution of viewers among advertisers allows the television network to satisfy contracts as planned and also increase ad-sales revenue. Spot scheduling is a very hard multi-period scheduling problem. Schedules have to be created such that advertiser’s campaign goals are met and ad-sales revenue is maximized. Each campaign has a specific target group of viewers and a unique set of constraints that have to be met. In addition, the number of viewers is uncertain. In this paper, we describe a practical approach that combines mathematical programming and time series methods to create daily schedules that are ready for broadcasting. This approach generates high quality schedules, according to standard business metrics and in comparison with the mathematical optimal bound. Our methods are used by leading networks and they produce substantial increases in revenue. Key words: scheduling, optimization, advertising, television–business. 1