Surface Binding of TOTAPOL Assists Structural Investigations of Amyloid Fibrils by Dynamic Nuclear Polarization NMR Spectroscopy

Dynamic nuclear polarization (DNP) NMR can enhance sensitivity but often comes at the price of a substantial loss of resolution. Two major factors affect spectral quality: low‐temperature heterogeneous line broadening and paramagnetic relaxation enhancement (PRE) effects. Investigations by NMR spectroscopy, isothermal titration calorimetry (ITC), and EPR revealed a new substantial affinity of TOTAPOL to amyloid surfaces, very similar to that shown by the fluorescent dye thioflavin‐T (ThT). As a consequence, DNP spectra with remarkably good resolution and still reasonable enhancement could be obtained at very low TOTAPOL concentrations, typically 400 times lower than commonly employed. These spectra yielded several long‐range constraints that were difficult to obtain without DNP. Our findings open up new strategies for structural studies with DNP NMR spectroscopy on amyloids that can bind the biradical with affinity similar to that shown towards ThT.     

Dielectric investigations of pristine and modified ZnO nanoparticles for energy storage devices

Pristine ZnO, Al-doped ZnO, and TiO₂ coated ZnO nanoparticles (NPs) were synthesized by the wet chemical precipitation technique. All the synthesized NPs were characterized using X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy. XRD analysis of pristine ZnO and Al-doped ZnO NPs revealed the hexagonal wurtzite structure with P6₃mc space group with no secondary phases and impurities. FESEM micrographs also depicted hexagonal grains with well-defined grain boundaries. TEM images showed hexagonal polyhedral shape for pure ZnO NPs and spherical shape dominating polyhedral particle for Al-doped ZnO NPs, and pseudospherical particles for TiO₂ coated ZnO NPs. Energy-dispersive X-ray spectroscopy of Al-doped ZnO indicates the eminent exchange of dopant in the lattice site of Zn. Dielectric Studies reveal the highest value of the dielectric constant and lowest value of dielectric loss for Al-doped ZnO as compared to pure and TiO₂-coated ZnO NPs. Suggesting Al-doped ZnO to be used as a dielectric material that can serve as a basic building block of the energy storage devices such as dielectric capacitor. TiO₂-coated ZnO NPs demonstrated higher AC conductivity in comparison to pure ZnO and Al-doped ZnO NPs suggesting their use as a conductive nanofiller materials in a polymer-based nanocomposite to achieve higher energy density.

     

A Study of Non-Recessed Hybrid Flexible Journal Bearing With Different Restrictors

For bearings operating under heavy loads, the elastic deformation of bearing surface induced by fluid film pressures can no longer be neglected as it is comparable to the order of magnitude of fluid film thickness. In the present work a theoretical study describing comparative performance of non-recessed hybrid journal bearing using different flow control devices has been carried out by considering bearing shell flexibility into the analysis. The relevant governing equations have been solved using finite element method. The comparative performance of non-recessed hybrid journal bearings of two separate configurations have been studied for various values of bearing flexibility parameter (([Cbar]_d)). The results have been presented for hole-entry type journal bearings compensated by capillary, orifice and constant flow valve restrictors and for a slot-entry type journal bearing, for the same set of values of operating and geometric parameters. The computed results indicates that in order to get an improved performance of non-recessed journal bearing, a proper selection of bearing flexibility parameter (([Cbar]_d)) along with type of flow control device (i.e., capillary, orifice, constant flow valve, slot etc.) and type of bearing configuration (symmetric/asymmetric) are essential.     

Influence of Alumina on Iron Ore Sinter Properties and Productivity in the Conventional and Selective Granulation Sintering Process

Iron ore sinter constitutes a major proportion of blast furnace burden. Hence, its quality and consistency have a significant impact on blast furnace performance. Iron ore fines are the main source for sinter, and the chemical composition of the iron ore fines, together with the thermal conditions that blends are subjected to, plays an important role in forming the primary melt during the sintering process and accordingly determines the sinter structure and quality. Therefore, considerable importance has been placed on the chemical composition and consistency of iron ore fines, particularly in terms of alumina content. Due to depletion of high grade iron ore resources, alumina content in the iron ore fines is expected to increase gradually. Ore with higher alumina content is usually expected to be detrimental in forming the sinter matrix, if sintered alone, due to the low reactivity of alumina bearing minerals and the high viscosity of primary melts. The selective granulation process is a new sintering process for high alumina iron ore fines, and can eliminate the adverse effects of ‘hard to sinter’ or ‘unsuitable – for ironmaking’ ores. In the present work laboratory sintering experiments have been carried out with iron ore fines of different alumina level (2.00 to 5.46 mass‐%) to know the influence of alumina on mineralogy, productivity, physical and metallurgical properties of sinter prepared by the conventional and the selective granulation process. With increasing alumina content in sinter of both the conventional and selective granulation process, the fractions of hematite and of silico‐ferrites of calcium and alumina (SFCA) as well as the pore phase increased whereas the magnetite and silicate phases decreased. With increase in alumina content sinter productivity and tumbler index (T.I.) decreased, and metallurgical properties like sinter RDI and reducibility improved. However, sinter of the selective granulation process showed better results compared to the conventional process.     

Effect of Iron Ore Pellet Size on its Properties and Microstructure

The properties of the pellets and their microstructure mainly depend on the raw material mix proportion, raw material chemical composition and the physicochemical conditions like the temperature and oxygen partial pressure within the induration machine. The pelletising plant products are in the size range of 8 to 16 mm. With increasing pellet size, the sintering intensity, thermo‐chemical conditions and formation of different phases vary across its cross section. The time required for varies reactions within the pellet is directly proportional to the pellet size. Because of differences in pellet size, the reduction and oxidation process takes place under different conditions resulting in different phases and microstructures. In this work, detailed studies were carried out on pellets of different size (8 to 16 mm) produced from a 4.2 Mtpa pellet plant for their physical, metallurgical and microstructural properties. It was observed that the pellets in the size range of +8 to ‐12 mm showed good strength and lower RDI. It was observed that the amount of hematite, magnetite, porosity, pore density, pore size and slag phase play a significant role on pellet strength and RDI.     

Numerical Technique for Resolving the Dual Phase Lag Heat Conduction in Thin Film Metal

Abstract

In this article, a three-time level finite difference scheme is used to resolve the dual phase lag’s (DPL) heat conduction in a micro scale gold film subjected to spontaneous temperature boundary conditions without knowing the heat flux. Finite difference analog of DPL equation on applying to the intermediate grid points of the computational domain results into a system of linear, algebraic equations which can be solved using Thomas’ algorithm to finally obtain the transient temperature solution distributions in the film. The solution predicted by the DPL model is compared with that obtained by the single-phase Cattaneo–Vernotte’s model. Further, the way in which non-Fourier’s temperature distributions affected by the diffusion due to the increase in Heat Conduction Model numbers agree with the predecessor’s published results. The results by both the models revealed a finite thermal wave speed in the film contrasting the infinite speed of heat propagation as stated by the classical Fourier’s thermal model. Low spatial step and higher order finite difference schemes are recommended for better accurate numerical results of the non-Fourier’s temperature distributions occurring in the very short transient period between the instants of the suddenly applied spatial temperature gradient and the reaching of the steady state conditions.     

Simultaneous Inhibition of PD-1 and Stimulation of CD40 Signaling Pathways by Anti-PD-L1/CD40L Bispecific Fusion Protein Synergistically Activate Target and Effector Cells

Bispecific antibodies (BsAbs) or fusion proteins (BsAbFPs) present a promising strategy for cancer immunotherapy. Numerous BsAbs targeting coinhibitory and costimulatory pathways have been developed for retargeting T cells and antigen presenting cells (APCs). It is challenging to assess the potency of BsAb that engages two different signaling pathways simultaneously in a single assay format, especially when the two antigen targets are expressed on different cells. To explore the potency of anti-PD-L1/CD40L BsAbFP, a fusion protein that binds to human CD40 and PD-L1, we engineered CHO cells as surrogate APCs that express T cell receptor activator and PD-L1, Jurkat cells with PD-1 and NFAT-luciferase reporter as effector T cells, and Raji cell with NFkB-luciferase that endogenously expresses CD40 as accessory B cells. A novel reporter gene bioassay was developed using these cell lines that allows anti-PD-L1/CD40L BsAbFP to engages both PD-1/PD-L1 and CD40/CD40L signaling pathways in one assay. As both reporters use firefly luciferase, the effects of activating both signaling pathways is observed as an increase in luminescence, either as a higher upper asymptote, a lower EC₅₀, or both. This dual target reporter gene bioassay system reflects potential mechanism of action and demonstrated the ability of anti-PD-L1/CD40L BsAbFP to synergistically induce biological response compared to the combination of anti-PD-L1 monovalent monoclonal antibody and agonist CD40L fusion protein, or either treatment alone. The results also showed a strong correlation between the drug dose and biological response within the tested potency range with good linearity, accuracy, precision, specificity and stability indicating properties, suggesting that this “three-cell-in-one” dual target reporter gene bioassay is suitable for assessing potency, structure-function and critical quality attributes of anti-PD-L1/CD40L BsAbFP. This approach could be used for developing dual target bioassays for other BsAbs and antibodies used for combination therapy.     

Do housing costs impact on poverty in rural areas?

Abstract

This research examines evidence for whether housing costs are more likely to be associated with poverty in rural than in urban Scotland. It reports the results from probit modelling of British Household Panel Survey data from 1999 to 2008. Empirical work is set in the context of understandings of factors associated with poverty, defined on an income basis, and specific features associated with rural locations. Attention is drawn to the way in which rurality is defined and that definition operationalized. The finding from the multivariate analysis is that a household’s housing costs do not appear to have a different association with its propensity to experience poverty in rural as opposed to urban Scotland. The paper sets out conclusions in the recognition of possible limitations and identifies ways in which the evidence can be extended.