Screening of β1- and β2-Adrenergic Receptor Modulators through Advanced Pharmacoinformatics and Machine Learning Approaches

Cardiovascular diseases (CDs) are a major concern in the human race and one of the leading causes of death worldwide. β-Adrenergic receptors (β1-AR and β2-AR) play a crucial role in the overall regulation of cardiac function. In the present study, structure-based virtual screening, machine learning (ML), and a ligand-based similarity search were conducted for the PubChem database against both β1- and β2-AR. Initially, all docked molecules were screened using the threshold binding energy value. Molecules with a better binding affinity were further used for segregation as active and inactive through ML. The pharmacokinetic assessment was carried out on molecules retained in the above step. Further, similarity searching of the ChEMBL and DrugBank databases was performed. From detailed analysis of the above data, four compounds for each of β1- and β2-AR were found to be promising in nature. A number of critical ligand-binding amino acids formed potential hydrogen bonds and hydrophobic interactions. Finally, a molecular dynamics (MD) simulation study of each molecule bound with the respective target was performed. A number of parameters obtained from the MD simulation trajectories were calculated and substantiated the stability between the protein-ligand complex. Hence, it can be postulated that the final molecules might be crucial for CDs subjected to experimental validation.     

Experimental analysis of spatio-temporal behavior of anodic dead-end mode operated polymer electrolyte fuel cell

During the anodic dead-end mode operation of fuel cells, the inert gases (nitrogen and water) present in the cathode side gas channel permeate to the anode side and accumulate in the anode gas channel. The inert gas accumulation in the anode decreases the fuel cell performance by impeding the access of hydrogen to the catalyst. The performance of fuel cell under potentiostatic dead-end mode operation is shown to have three distinct regions viz. time lag region, transient current region and a steady state current region. A current distribution measurement setup is used to capture the evolution of the current distribution as a function of time and space. Co- and counter-flow operations of dead-end mode confirm the propagation of inert gas from the dead-end of anode channel to the inlet of anode. Experiments with different oxidants, oxygen and air, under dead-end mode confirm that nitrogen which permeates from cathode to anode causes the performance drop of the fuel cell. For different starting current densities of 0.15 A cm⁻², 0.3 A cm⁻² and 0.6 A cm⁻² the inert gas occupies 35%, 45% and 57%, respectively of anode channel volume at the end of 60 min of dead-end mode operation.     

A direct borohydride fuel cell employing Prussian Blue as mediated electron-transfer hydrogen peroxide reduction catalyst

A direct borohydride-hydrogen peroxide fuel cell employing carbon-supported Prussian Blue (PB) as mediated electron-transfer cathode catalyst is reported. While operating at 30 °C, the direct borohydride-hydrogen peroxide fuel cell employing carbon-supported PB cathode catalyst shows superior performance with the maximum output power density of 68 mW cm⁻² at an operating voltage of 1.1 V compared to direct borohydride-hydrogen peroxide fuel cell employing the conventional gold-based cathode with the maximum output power density of 47 mW cm⁻² at an operating voltage of 0.7 V. X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Analysis (EDAX) suggest that anchoring of Cetyl-Trimethyl Ammonium Bromide (CTAB) as a surfactant moiety on carbon-supported PB affects the catalyst morphology. Polarization studies on direct borohydride-hydrogen peroxide fuel cell with carbon-supported CTAB-anchored PB cathode exhibit better performance with the maximum output power density of 50 mW cm⁻² at an operating voltage of 1 V than the direct borohydride-hydrogen peroxide fuel cell with carbon-supported Prussian Blue without CTAB with the maximum output power density of 29 mW cm⁻² at an operating voltage of 1 V.     

Nafion and modified-Nafion membranes for polymer electrolyte fuel cells: An overview

Polymer electrolyte fuel cells (PEFCs) employ membrane electrolytes for proton transport during the cell reaction. The membrane forms a key component of the PEFC and its performance is controlled by several physical parameters, viz. water up-take, ion-exchange capacity, proton conductivity and humidity. The article presents an overview on Nafion membranes highlighting their merits and demerits with efforts on modified-Nafion membranes. Energy security refers to various security measures that a given nation, or the global community as a whole, must carryout to maintain an adequate energy supply     

Mapping the total phosphorus concentration of biosolid amended surface soils using LANDSAT TM data

Conventional methods for soil sampling and analysis for soil variability in chemical characteristics are too time-consuming and expensive for multi-seasonal monitoring over large-scale areas. Hence, the objectives of this study are: 1) to determine changes in chemical concentrations of soils that are amended with treated sewage sludge; and 2) to determine if LANDSAT TM data can be used to map surface chemical characteristics of such amended soils. For this study, we selected two fields in NW Ohio, designated as F34 and F11, that had been applied with 34 and 11 ton acre^− 1 of biosolids, respectively. Soil samples from a total of 70 sampling locations across the two fields were collected one day prior to LANDSAT 5 overpass and were analyzed for several elemental concentrations. The accumulation of Ba, Cd, Cu, S and P were found to be significantly higher in the surface soils of field F34, compared to field F11. Regression equations were established to search for algorithms that could map these five elemental concentrations in the surface soils using six, dark-object-subtracted (DOS) LANDSAT TM bands and the 15 non-reciprocal spectral ratios derived from these six bands for the May 20, 2005, LANDSAT 5 TM image. Phosphorus (P) had the highest R² adjusted value (67.9%) among all five elements considered, and the resulting algorithm employed only spectral ratios. This model was successfully tested for robustness by applying it to another LANDSAT TM image obtained on June 5, 2005. Our results enabled us to conclude that LANDSAT TM imagery of bare-soil fields can be used to quantify and map the spatial variation of total phosphorous concentration in surface soils. This research has significant implications for identification and mapping of areas with high P, which is important for implementing and monitoring the best phosphorous management practices across the region.     

Can Agile and Traditional Systems Development Approaches Coexist? An Ambidextrous View

Emerging evidence seems to indicate that most systems development organizations are attempting to utilize both agile and traditional approaches. This study aims to understand the reasons organizations feel the need for this unlikely juxtaposition and the organizational challenges in sustaining the opposing cultures. Drawing on the extensive literature in organizational theory and management, we advocate ambidexterity as a viable solution to systems development organizations attempting to harness the benefits of both agile and traditional development.     

A study of nonisothermal austenite formation and decomposition in Fe-C-Mn alloys

Experiments using a hot-stage confocal scanning laser microscope (CSLM) have been carried out to observe phase transformations in two steels: Si-killed resulfurized Fe-0.38 wt pct C-1.43 wt pct Mn and Al-killed Fe-0.20 wt pct C-0.87 wt pct Mn. Austenite formation during continuous heating was investigated on the surface of samples that were etched to reveal the ferrite and pearlite regions. It was found that the austenite precipitated first at the pearlite colonies and subsequently in the ferrite phase. The measured advance rates of the γ/pearlite front were roughly twice those of the γ/α front and both interfaces were found to be curved. The γ/pearlite migration rate was found to be in qualitative agreement with published rate equations for isokinetic austenite formation where diffusion is the rate-limiting step. Austenite decomposition was studied during cooling. Widmanstätten ferrite laths precipitate as distinct colonies from the existing allotriomorphic ferrite phase but then also at MnS precipitates. The electron backscatter diffraction (EBSD) analysis showed that all of the laths in a particular colony exhibit similar orientation to one another but a slightly different orientation than the parent allotriomorph, supporting a sympathetic nucleation mechanism. The growth rate of the laths was found to vary widely within a range of 1.5 to 11 μm/s. The ferrite formation is finally halted by impingement with other advancing fronts. The results are presented in a phenomological discussion, with some quantitative analysis of the transformation kinetics.     

DIFFUSION COEFFICIENT OF OXYGEN IN LIQUIDS

The laminar dispersion of a solute in a capillary tube is used to measure diffusion coefficient of oxygen in liquids. A Polarographic type oxygen microelectrode is used to detect the pulse. Such a procedure overcomes the problems of measuring dissolved gases and makes it possible to apply this well known technique to oxygen-liquid systems. The results are in agreement with literature values     

Soil line transformation based relative radiometric normalization

Relative radiometric normalization is a prerequisite for multi‐temporal remotely sensed data analysis. Dark object subtraction (DOS) and pseudo‐invariant feature (PIF) methods are two commonly employed scene‐based methods for relative radiometric normalization. Both these methods have known limitations. The authors describe a soil line transformation method for multi‐date relative radiometric normalization, which circumvents the limitations of the DOS and PIF methods.