AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Secure And Efficient Defense Strategy Against Energy Exhausting Attacks In Wsn

One of the most critical concerns in WSN design is security and energy-efficiency problem and the wireless sensor networks is resilience against malicious attacks. Since energy is the most precious resource for these networks, Denial of sleep attacks is recognized as one of the most serious threats. Such attacks exhaust power supply of sensor nodes and can reduce the sensor lifetime from years to days. Authentication and encryption solutions have been proposed to protect the network from denial of sleep attacks. Though, the resources constraint motivates the use of simpler solutions to the same security challenges. In this paper, we survey different types of denial of sleep attacks and we propose a cross layer energy efficient security mechanism to protect the network from these attacks. The cross layer interaction between network Mac and physical layers is mainly exploited to identify the intruders nodes and prevent sensor nodes from energy exhaust attacks. Simulation results indicate that our proposal is energy efficient and can significantly reduce the effect of denial of sleep attacks.</jats:p

EXPERIMENTAL INVESTIGATION OF TOOL WEAR AND SURFACE ROUGHNESS BY THE INFLUENCE OF VARIOUS CUTTING FLUIDS IN TURNING OPERATION

The main objective of this work is to understand how the tool wear and surface roughness are influenced by various cutting fluids and machining parameters in turning EN8 SAE/AISI 1040 steel. Cutting fluids should be chosen by acidic nature test and viscosity test. It should have proper lubricity and act as a coolant. Vegetable oils like groundnut, coconut, and sunflower are considered to check their properties. Among these oils, groundnut and coconut oils were selected based on their properties. Experimental studies on the performances of both newly developed environmentally friendly vegetable-based cutting fluids (coconut oil and ground nut oil) and commercial cutting fluids in turning processes were reported. Performances of cutting fluids were compared with respect to surface roughness, cutting and feed forces and tool wear during longitudinal turning ofEN8 SAE/AISI 1040 steel. Experimental results were also compared with dry cutting conditions. Based on the results, the best-cutting fluid was selected.</jats:p

Influence of Electric Field Distribution on 33kv Non-Ceramic Insulator with Different Shed Configurations using 3D Finite Element Method

In last decade, influence of electric field (E-field) distribution is plays a major concern in estimating the service life of Non-cermaic insulators. One of the foremost troubles met by the utilities is the breakdown of insulator owing toward high electrical stress on end fittings. The present work is intended to focus on the impact of different shed configurations on 33kV Non-Ceramic insulators by 3-Dimensional (3D) Finite Element Method (FEM). Totally seven different shed configurations of 3D simulation studies is performed on 33kV non-ceramic insulators. Optimum result is obtained by alternate shed configured insulator and the first shed near to the metal end fittings. It is whispered that obtained results will be helpful to the utility and design engineers.</jats:p

Isolation and screening of keratinse producing bacteria from chicken farm bed

Currently, there are about 195 nations in the world, with a population of 7.8 billion. This much higher the population directly influences higher food demand. Due to this interlink massive amount of food waste has been collected from the meat industries; especially poultry plays a major role by discharging feathers into dumps. There are about 8.5 billion tons of feathers that are wasted every year which lead to high global environmental risk and cause different human disease. This high risk is due to typical structure of feather. They have a matrix protein called keratin that makes degradation more tedious under normal condition; they are insoluble in nature with high rigidity due to the disulfide bridges. By extraction of keratin from these waste feathers are used for multipurpose such as cosmetics, biomedical, textile use, bio-fertilizers etc. In addition, as per trend by utilizing nature’s gift the microorganisms we can breakdown these matrix proteins easily. By this environmental friendly technique our works gets easier and are also cost effective. By consumption of keratin as substrate some microorganisms produce an extracellular enzyme called keratinase which has the ability to cleave the protein. The produced keratinase is a wealth out of waste which has wide biochemical properties and also used for waste water treatments. On whole the feather considers as waste is completely turned to verity of useful products ubiquitous like biodiesel, biofertilizer, biodegradable plastics, biofilms, skin, hair and other biomedical treatments.</jats:p

Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer

Lung cancer is the leading type of malignancy in terms of occurrence and mortality in the global context. STAT3 is an oncogenic transcription factor that is persistently activated in many types of human malignancies, including lung cancer. In the present report, new oxadiazole conjugated indazoles were synthesized and examined for their anticancer potential in a panel of cancer cell lines. Among the new compounds, 2-(3-(6-chloro-5-methylpyridin-3-yl)phenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole (CHK9) showed consistently good cytotoxicity towards lung cancer cells with IC50 values ranging between 4.8–5.1 µM. The proapoptotic effect of CHK9 was further demonstrated by Annexin-FITC staining and TUNEL assay. In addition, the effect of CHK9 on the activation of STAT3 in lung cancer cells was examined. CHK9 reduced the phosphorylation of STAT3Y705 in a dose-dependent manner. CHK9 had no effect on the activation and expression of JAK2 and STAT5. It also reduced the STAT3-dependent luciferase reporter gene expression. CHK9 increased the expression of proapoptotic (p53 and Bax) proteins and decreased the expression of the antiapoptotic (Bcl-2, Bcl-xL, BID, and ICAM-1) proteins. CHK9 displayed a significant reduction in the number of tumor nodules in the in vivo lung cancer model with suppression of STAT3 activation in tumor tissues. CHK9 did not show substantial toxicity in the normal murine model. Overall, CHK9 inhibits the growth of lung cancer cells and tumors by interfering with the STAT3 signaling pathway.</jats:p