The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2)

Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, brain-penetrating kinase inhibitors were selected, and their structure was appropriately modified to assemble a cereblon-targeting PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells. However, data regarding the degradation of the target protein are inconclusive. The reasons for the inefficient degradation of the target are further discussed.     

Fabrication of zinc‐loaded hollow glass microspheres (HGMs) for hydrogen storage

The greatest challenge for a feasible hydrogen economy lies on the production of pure hydrogen and the materials for its storage with controlled release at ambient conditions. Hydrogen with its great abundance, high energy density and clean exhaust is a promising candidate to meet the current global challenges of fossil fuel depletion and green house gases emissions. Extensive research on hollow glass microspheres (HGMs) for hydrogen storage is being carried out world‐wide, but the right material for hydrogen storage is yet underway. But many other characteristics, such as the poor thermal conductivity etc. of the HGMs, restrict the hydrogen storage capacity. In this work, we have attempted to increase the thermal conductivity of HGMs by ZnO doping. The HGMs with Zn weight percentage from 0 to 10 were prepared by flame spheroidization of amber‐colored glass powder impregnated with the required amount of zinc acetate. The prepared HGMs samples were characterized using field emission‐scanning electron microscope (FE‐SEM), environmental SEM (ESEM), high‐resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy and X‐ray diffraction (XRD) techniques. The deposition of ZnO on the microsphere walls was observed using FE‐SEM, ESEM and HRTEM which was further confirmed using the XRD and ultraviolet–visible absorption data. The hydrogen storage studies done on these samples at 200 °C and 10‐bar pressure for 5 h showed that the hydrogen storage increased when the Zn percentage in the sample increased from 0 to 2%. The percentage of zinc beyond 2, in the microspheres, showed a decline in the hydrogen storage capacity. The closure of the nanopores due to the ZnO nanocrystal deposition on the microsphere surface reduced the hydrogen storage capacity. The hydrogen storage capacity of HAZn2 was found 3.26 wt% for 10‐bar pressure at 200 °C. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimized and load balanced clustering for wireless sensor networks to increase the lifetime of WSN using MADM approaches

Wireless Networks - The power utilization has verified as a major problem in wireless sensor networks (WSNs). Many researchers have provided efficient solutions for power utilization. Clustering is...     

Dual role of grass clippings as buffering agent and biomass during anaerobic co-digestion with food waste

Clean Technologies and Environmental Policy - There is a dire need to replace the chemical buffers that regulate the redox environment in single-stage anaerobic digestion of food waste. Hence, the...     

Kinetic modelling and microbial community assessment of anaerobic biphasic fixed film bioreactor treating distillery spent wash

Anaerobic digestion, microbial community structure and kinetics were studied in a biphasic continuously fed, upflow anaerobic fixed film reactor treating high strength distillery wastewater. Treatment efficiency of the bioreactor was investigated at different hydraulic retention times (HRT) and organic loading rates (OLR 5-20 kg COD m⁻³ d⁻¹). Applying the modified Stover-Kincannon model to the reactor, the maximum removal rate constant (U_max) and saturation value constant (K_B) were found to be 2 kg m⁻³ d⁻¹ and 1.69 kg m⁻³ d⁻¹ respectively. Bacterial community structures of acidogenic and methanogenic reactors were assessed using culture-independent analyses. Sequencing of 16S rRNA genes exhibited a total of 123 distinct operational taxonomic units (OTUs) comprising 49 from acidogenic reactor and 74 (28 of eubacteria and 46 of archaea) from methanogenic reactor. The findings reveal the role of Lactobacillus sp. (Firmicutes) as dominant acid producing organisms in acidogenic reactor and Methanoculleus sp. (Euryarchaeotes) as foremost methanogens in methanogenic reactor.     

Synthesis of ultra-small silicon nanoparticles by femtosecond laser ablation of porous silicon

We report a detailed study on the synthesis of ultra-small (1–10 nm) colloidal silicon nanoparticles (Si NPs) by ablating porous silicon (pSi) in acetone using femtosecond laser pulses. Porous silicon is considered as a target material for ablation because it contains a large number of light emitting silicon nanoparticles. The pSi samples were prepared by anodic etching of silicon in aqueous HF solution for different etching current densities. Transmission electron microscope measurements confirmed the successful formation of well-isolated spherical silicon nanoparticles. The average size of spherical NPs were estimated to be ~7.6, ~7, and ~6 nm when anodic etching current densities of 5, 10, and 20 mA/cm² were used respectively for preparing pSi targets. The crystallinity of these Si NPs was confirmed by selective area electron diffraction and Raman spectroscopy measurements. The observed blue shift in the absorption and emission spectra are attributed to reduction in the average particle size with increase in etching current density. These Si NPs may be useful for fabricating low-dimensional microelectronic compatible photonic devices.     

Effect of hydrophilic and hydrophobic polymers on permeation of S-amlodipine besylate through intercalated polymeric transdermal matrix: 3(2) designing,optimization and characterization

Objective: Innovation in material science has made it possible to fabricate a pharmaceutical material of modifiable characteristics and utility, in delivering therapeutics at a sustained/controlled rate. The objective of this study is to design and optimize the controlled release transdermal films of S-Amlodipine besylate by intercalating hydrophilic and hydrophobic polymers.

Methods: 3(2) factorial design and response surface methodology was utilized to prepare formulations by intercalating the varied concentration of polymers(A) and penetration enhancer(B) in solvent. The effect of these independent factors on drug release and flux was investigated to substantiate the ex-vivo, stability and histological findings of the study.

Results: FTIR, DSC revealed the compatibility of drug with polymers; however, the semicrystallinity in drug was observed under PXRD. SEM micrographs showed homogeneous dispersion and entanglement of drug throughout the matrix. Results from the permeation study suggested the significant effect of factors on the ex vivo permeation of drug. It was observed that drug release was found to be increased with an increase in hydrophilic polymer concentration and PE. The formulations having polymers (EC:PVPK-30) at 7:3 showed maximum drug release with highest flux (102.60?±?1.12?µg/cm²/h) and permeability coefficient (32.78?±?1.38?cm/h). Significant effect of PE on lipid and protein framework of the skin was also observed which is responsible for increased permeation. The optimized formulation was found to be stable and showed no-sign of localized reactions, indicating safety and compatibility with the skin.

Conclusion: Thus, results indicated that the prepared intercalated transdermal matrix can be a promising nonoral carrier to deliver effective amounts of drug.