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Amino acid side chains are key to fine-tuning the microenvironment polarity in proteins composed of polar amide bonds. Here, we report that substituting an oxygen atom of the backbone amide bond with sulfur atom desolvates the thioamide bond, thereby increasing its lipophilicity. The impact of such local desolvation by O to S substitution in proteins was tested by synthesizing thioamidated variants of Pin1 WW domain. We observe that a thioamide acts in synergy with nonpolar amino acid side chains to reduce the microenvironment polarity and increase protein stability by more than 14 °C. Through favorable van der Waals and hydrogen bonding interactions, this single atom substitution significantly stabilizes proteins without altering the amino acid sequence and structure of the native protein.

Silica nanospheres have been explored much for drug delivery, photocatalysis, sensors and energy storage applications. It also acts as a template for Surface-Enhanced Raman Spectroscopy (SERS) substrates. Uniform nanostructures at low cost with high reproducibility are the major challenges in SERS substrate fabrication. In the present work, silica nanospheres were synthesized using stober method and deposited on to glass slides using Vertical deposition techniques. Different size/thickness of Silver (Ag) nanoparticles were deposited onto silica thin films using sputter deposition technique. The monodispersity of silica nanospheres and size of silver nanoparticles (10 nm, 20 nm and 30 nm) were confirmed by FESEM analysis. The structural properties were confirmed through XRD. UV–Vis analysis revealed that the plasmonic properties of Ag@SiO2 give high surface plasmons for 30 nm thickness of silver. The binding energy of Ag@SiO2 confirmed through XPS spectrum. The fabricated SERS substrates were used to detect Rhodamine 6G (R6G), Methylene blue (MB), Methylene violet (MV) and Methyl orange dyes as an analyte molecule with a limit of detection at about 10−11 mol/L. The addition of SiO2 nanospheres decreases the Ag oxidation rate and increases their stability. The maximum enhancement factor (1.5 × 107) achieved for 30nm thickness of Ag@SiO2. The results and technique establish the potential applications and reproducible SERS substrate.

Barium yttrium phosphate (BYP) phosphor doped with trivalent praseodymium ions (BaY(1-x) (PO4 )3 :Pr3+ (x = 0, 0.01, 0.05, 0.1, 0.15, and 0.2 wt%) was synthesized using a high temperature solid-state reaction method. Structural properties were analyzed through X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. XRD patterns confirmed the structure of the synthesized phosphor and average crystalline size was estimated (approximately 63.8 A). Vibrational functional groups were identified using FTIR spectroscopy. The emission spectrum was recorded under an 444 nm excitation wavelength, which showed various emission transitions of Pr3+ ions. Commission Internationale de l'eclairage coordinates, colour purity, and colour correlated temperature values were calculated for the BYP:Pr3+ phosphors and these coordinate values fell in the yellow region of the visible spectrum.

The methylation of cytosine residues that precede adenine/thymine or other cytosine nucleotides instead of guanine in DNA is known as non-CpG methylation. It is a pronounced epigenetic modification with a central role in gene regulation similar to CpG methylation. Due to technological limitations, the locus-specific role of non-CpG methylation was scarcely understood. At present, high-throughput analyses and improved enrichment methods can elucidate the role of genome-wide non-CpG methylation distributions. Although the functional basis of non-CpG methylation in regulating gene expression control is known, its role in cancer development is yet to be ascertained. This review sheds light on the possible mechanism of non-CpG methylation in embryos and developed tissues with a special focus on cancer development and progression. In particular, the maintenance and alteration of non-CpG methylation levels and the crucial factors that determine this level of non-CpG methylation and its functional role in cancer are discussed.

Cornea is the outmost layer of an eye helps to focuses the light rays towards the retinal layer of the eye. The irregular thickness of the corneal layer results in poor focus of light rays over the retinal layer and hence it results in blur vision. Lasik is a surgical procedure made for correcting the irregular thickness of the cornea to certain extent for making the light rays to fall exactly on the retinal layer. In order to undergo with a lasik procedure, an eye must have sufficient thickness of corneal layer to tolerate the medical procedure. Similarly, the corneal layers are can't be operated after certain extent. Therefore there is a need for pre-surgical planning by measuring the thickness availability of the corneal layer. The proposed work is engaged to identify the three major boundaries of the corneal layer using a capsule network based algorithm. The proposed work is segregated as preprocessing, classification and segmentation. A hybrid speckle noise reduction filter was employed in the preprocessing stage to minimize the noise presence in the corneal images. Then the images are moved further to train the ClassCaps algorithm to classify a better noiseless image from the group of test images. The modified SegCaps algorithm was utilized in this work to detect the three major boundaries of the cornea from the noiseless image output from the ClassCaps algorithm. The performance of the proposed algorithm was verified with the several classification and segmentation algorithm to prove its accuracy.

Solid lipid nanoparticles (SLNs) are in submicron size range nanoparticles and are made of biocompatible and biodegradable materials (mainly composed of lipids and surfactants) capable of incorporating both lipophilic and hydrophilic drugs. SLNs are also considered as substitute to other colloidal drug systems, also used as controlled systems and targeted delivery. SLNs can be considered as an alternative for oral drug delivery vehicle to improve the oral bioavailability of drugs, associated reduction of drug toxicity and stability of drug in both GIT and plasma. There are different techniques used for the preparation of SLNs. Generally, the preparation of SLNs and any other nanoparticle system necessitates a dispersed system as precursor; otherwise particles are produced through the use of a particular instrumentation. This review provides the summary on the techniques or methods used for the development of SLNs of poorly water soluble drugs for improved drug delivery. Keywords: Solid lipid nanoparticles, controlled delivery, precursor, techniques.

From last thirty years, solid lipid nanoparticles (SLNs) gain much importance as drug delivery vehicle for enhanced delivery of the drugs, proteins, nutraceuticals and cosmetics. SLNs defined as a submicron size range nanoparticle with below 1000 nm and are mainly composed of lipids and surfactants, capable of incorporating both lipophilic and hydrophilic drugs. SLNs also used as controlled systems, targeted delivery and altered therapeutic efficacy purpose. A wide variety of methods such as double emulsion, solvent evaporation, ultra sonication, high-pressure homogenization and microemulsion used for SLNs production. This review provides the significance of SLNs in drug delivery with highlighting on selection of excipients, drug release mechanism, principles and limitations associated with their physicochemical and surface morphological characterization. Keywords: Solid lipid nanoparticles, enhanced delivery, preparation, characterization, application.

Proses Uji bahan material Gear Sprocket meliputi proses pemotongan material yang digunakan sebagai sampel Uji Bahan yang dilakukan pencampuran maupun tidak dilakukan pencampuran. Dalam sampel yang dilakukan pencampuran yaitu Logam dasar yang sudah dilakukan pemotongan dengan perbandingan nilai 10:2 Ons Material Gear Sprocket 10 dan Material Timah 2 Ons, akan dilakukan peleburan untuk proses pemaduan/mempersatukan kedua jenis material tersebut sebagai bahan material sampel Uji bahan dengan pencampuran tersebut, sedangkan sampel material Gear Sprocket yang tidak dilakukan pencampuran juga diambil nilai beban 10 Ons, untuk sebagai sampel pengujian yang tidak dilakukan pencampuran tersebut. Data hasil pengujian dari Sampel material Gear Sprocket dengan pencampuran Timah dengan empat kali pengujian dari beberapa bagian permukaan yang berbeda didapat nilai 51,5, 55, 50, 53 kgf. Sedangkan Sampel material Gear Sprocket yang tanpa pencampuran Timah didapat hasil nilai 50, 51, 50, 50 kgf. didalam pemaduan Material Timah dengan logam dasar Gear Sprocket dengan perbandingan Material Timah 2 Ons dan Material Gear Sprocket 10 Ons didapat hasil kekerasan yang tidak stabil, sehingga nilai yang didapat dari material yang dilakukan perlakuan tersebut didapat nilai yang kurang memungkinkan, sedangkan nilai uji bahan dari Material Gear Sprocket yang tidak dilakukan pemaduan didapat hasil yang baik dari tiap-tiap permukaanya walaupun nilai kekerasannya sedikit lebih kecil dari hasil material yang dilakukan perlakuan.

Aims To analyse the rate of heart failure hospitalization for older adults prescribed a sodium-glucose co-transporter-2 (SGLT2) inhibitor. Materials and methods The study cohort included adults aged 66 years and older diagnosed with diabetes mellitus in Ontario, Canada, between July 2015 and March 2019, who received either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor. The primary outcome was a composite of heart failure hospitalization and all-cause mortality. Secondary outcomes included diabetic ketoacidosis and hypoglycaemia. Results A total of 29 916 adults prescribed an SGLT2 inhibitor were compared with 29 916 adults prescribed a DPP-4 inhibitor. The mean age was 72 years, 60% were men, the baseline glycated haemoglobin concentration was 8.2% and the baseline creatinine was 89 μmol/L. The incidence rate of the primary outcome was 19/1000 person-years for adults prescribed an SGLT2 inhibitor compared to 38/1000 person-years in those prescribed a DPP-4 inhibitor. This resulted in a hazard ratio (HR) of 0.49 (95% confidence interval [CI] 0.45, 0.54) and a rate difference (RD) of 19 fewer events per 1000 person-years (RD -19 [95% CI -22, -17]). Patients prescribed an SGLT2 inhibitor also had a lower rate of hypoglycaemia (HR 0.61 [95% CI 0.46, 0.81); RD -1.6 [95% CI -2.4, -0.8]), but a higher rate of diabetic ketoacidosis (HR 1.84 [95% CI 1.26, 2.70]; RD 1.0 [95% CI 0.4, 1.6]). Conclusions Older adults prescribed an SGLT2 inhibitor had a lower rate of heart failure hospitalization or death, and a lower rate of hypoglycaemia, but an increased rate of diabetic ketoacidosis compared to older adults prescribed a DPP-4 inhibitor.

Oxyfluoride (P2O5 + Bi2O3 + Na2CO3 + SrCO3 + ZnF2) glasses doped with different dysprosium (Dy3+) ion concentrations (0.5, 1.0, 1.5 & 2 mol %) have been synthesized using conventional melt quenching technique. The Physical and optical parameters such as density (ρ), refractive index (n), polaron radius (rp), interionic distance (ri), field strength (F), electron polarizability (αe), molar refractivity (RM), reflection loss (R), etc., were evaluated. The X-ray diffractograms were recorded in the 10–900 region, showed amorphous nature. Surface morphological studies were performed with SEM and elemental analysis has also been performed with EDS. The absorption spectra consist of a few well-defined high intense bands in the UV–Vis-NIR region. The optical band gaps were estimated from the tauc’s plots drawn from the absorption spectra and obtained values exhibited nonlinear behaviour with dopant ion concentration. The emission spectra were recorded by monitoring the excitation wavelength at 453 nm which consists of three emission bands at 487, 557 and 667 nm, due to f-f characteristic transitions of Dy3+ ion. The Judd-Ofelt and radiative parameters have been calculated from absorption and luminescence spectra. It has been noticed that the concentration quenching effect was observed for higher concentrations (1.5 and 2.0 mol %) in the present glass series. The emission intensity ratio between yellow and blue color bands and CIE color coordinates were evaluated. The correlated color temperature (CCT) and color purity (CP) has been evaluated using CIE 1931 chromaticity diagram. The ZnBiNaPSr: Dy1.0 glass exhibits superior luminescent properties than other concentrations and it was found to be the most prominent device for white light applications.

Curcumin is a natural polyphenol obtained from Curcuma longa which has gained much attention in medical and scientific fields and is known for its wide range of therapeutic applications. But the natural herb mixtures with high subatomic sizes have low retention limits which does not permit the restorative medication to cross the lipid membranes, subsequently bringing about low bioavailability with confined proficiency. Nanobiotechnology has overcome the drawbacks of curcumin delivery to its targeted site through the use of antioxidant-rich, biodegradable SLNs as drug delivery vehicle with specificity and expanded bioavailability that will encourage the dynamic release of therapeutic ingredients into the body. Herein, optimized curcumin-loaded SLNs (CuSLNs) were developed. The morphological analysis of SEM has shown the average particle size was found to be in the range of 71–112 nm. The physicochemical characteristics of optimized CuSLNs were particle size of 106 nm, zeta potential of − 54 mV, polydispersity index of 0.429 which have confirmed the nanoparticle stability. The FTIR, DSC, and XRD results have suggested the lipids are compatible and confirmed the complete solubilization of curcumin in the lipid phase. Encapsulation efficiency and drug loading capacity of optimized formulation were 88.22 and 13.13, respectively. In vitro release studies have shown the controlled drug release rate of 88% compared with free curcumin and 81% of in vitro antioxidant activity which is compared with the ascorbic acid. The studies confirmed that the formulation of CuSLNs is a promising drug delivery system with controlled drug release, improved bioavailability with good stability.

A new strategy for the activation of glycosyl halide donors to be utilized in glycosylation reactions is presented, utilizing the ferrocenium (Fc) complexes [FcB(OH)2]SbF6 and FcBF4 as promoters. The scope of the new system has been investigated using glycosyl chloride and glycosyl fluoride donors in combination with common glycosyl acceptors, such as protected glucose. The corresponding glycosylation products were formed in 95 to 10% isolated yields with α/β ratios ranging from 1/1 to β only (2 to 14 h reaction time at room temperature, 40 to 100% ferrocenium promoter load).

A new preconcentration method which utilises a mixture of cationic and anionic surfactants for separation and spectrophotometric determination of iron and cobalt simultaneously has been developed. The metal ions, iron and cobalt were complexed with thiocyante. The hydrophobic complexes of iron and cobalt were then extracted into catanionic mixed micelles of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl sulphate (SDS). Different parameters like concentration of HCl, concentration of thiocyanate, concentrations of the surfactants (CTAB and SDS), equilibration temperature and time were studied to get maximum efficiency. The linear ranges of Fe3+ and Co2+ were found to be 0.139 – 0.838 μg mL–1 and 5.89 – 35.4 μg mL–1, respectively the detection limits obtained were 1.54 ng mL–1 and 6.18 ng mL–1. The developed procedure has been employed for the retrieval of Fe3+ and Co2+ in water samples successfully (tap water and sea water). 98 – 107% recoveries were obtained.

Background: Local anesthetics are widely used to decrease sensitivity to pain in specific regions of the body while performing medical tasks. Many studies have probed the mechanism of action of local anesthetics but still many questions remain. (2R - (-) 2 - (2, 6-dimethylphenylaminocarbonyl) - 1 – methyl piperidinium chloride (DAMP), is an extensively used amide-type local anesthetic. Objective: This study aims at revealing the various electrophysical and chemical properties of the title compound. This study will be useful for future research by pharmacologists. Method: Density Functional Theory (DFT) computations were executed using Gaussian’09 program package and were optimized with the B3LYP /6-311+G (d, p) basis set. Natural bond orbital (NBO) analysis was carried out with version 3.1. Normal Coordinate Analysis (NCA) was used to systematically calculate the harmonic vibrational wavenumbers. Molecular docking simulations were carried out to understand the pharmacokinetic behavior of the drug. Results: The presence of strong N-H…Cl intra molecular hydrogen bonding was evidently revealed from the FT-IR spectrum due to the shifting of NH stretching wavenumber. Stability of the molecule arising from hyper conjugative interactions exhibits the bioactivity of the molecule by natural bond orbital analysis. The title molecule binds to the inner pore and blocks voltage - gated sodium channels in peripheral neurons. Conclusion: A detailed molecular picture of DAMP and its interactions were obtained by modeling analysis, IR, Raman, and UV-Vis spectroscopy. The geometrical parameters agree well with the XRD data. NBO analysis indicates the bioactivity of the molecule. The HOMO-LUMO energy gap indicates the possibility of intramolecular charge transfer of the molecule. From the ligand docking studies it is concluded that the title molecule binds to the inner pore and blocks voltage - gated sodium channels in peripheral neurons.

Background Pathological forms of TAR DNA-binding protein 43 (TDP-43) are present in motor neurons of almost all amyotrophic lateral sclerosis (ALS) patients, and mutations in TDP-43 are also present in ALS. Loss and gain of TDP-43 functions are implicated in pathogenesis, but the mechanisms are unclear. While the RNA functions of TDP-43 have been widely investigated, its DNA binding roles remain unclear. However, recent studies have implicated a role for TDP-43 in the DNA damage response. Methods We used NSC-34 motor neuron-like cells and primary cortical neurons expressing wildtype TDP-43 or TDP-43 ALS associated mutants (A315T, Q331K), in which DNA damage was induced by etoposide or H2O2 treatment. We investigated the consequences of depletion of TDP-43 on DNA repair using small interfering RNAs. Specific non homologous end joining (NHEJ) reporters (EJ5GFP and EJ2GFP) and cells lacking DNA-dependent serine/threonine protein kinase (DNA-PK) were used to investigate the role of TDP-43 in DNA repair. To investigate the recruitment of TDP-43 to sites of DNA damage we used single molecule super-resolution microscopy and a co-immunoprecipitation assay. We also investigated DNA damage in an ALS transgenic mouse model, in which TDP-43 accumulates pathologically in the cytoplasm. We also examined fibroblasts derived from ALS patients bearing the TDP-43 M337V mutation for evidence of DNA damage. Results We demonstrate that wildtype TDP-43 is recruited to sites of DNA damage where it participates in classical NHEJ DNA repair. However, ALS-associated TDP-43 mutants lose this activity, which induces DNA damage. Furthermore, DNA damage is present in mice displaying TDP-43 pathology, implying an active role in neurodegeneration. Additionally, DNA damage triggers features typical of TDP-43 pathology; cytoplasmic mis-localisation and stress granule formation. Similarly, inhibition of NHEJ induces TDP-43 mis-localisation to the cytoplasm. Conclusions This study reveals that TDP-43 functions in DNA repair, but loss of this function triggers DNA damage and is associated with key pathological features of ALS.

Co-rich ZnCo2O4 (ZCO) two-dimensional (2D) nanosheets are decorated with highly porous, glucose-derived, zero-dimensional (0D) interconnected network-like carbon nanospheres (CNS) using an in situ hydrothermal method. The content of CNS in the reaction is varied to produce two different composites (CNS@ZCO-I and CNS@ZCO-II). Their physicochemical properties are examined and compared with those of the pristine-CNS and ZCO samples. The non-stoichiometry of the elements in ZCO of the composites is quantified by X-ray diffraction using a Reitveld refinement and X-ray photoelectron spectroscopy. CNS@ZCO-II is found to be Co-rich in ZnCo2O4 compared to the other samples. The high surface area of the CNS and non-stoichiometry of Zn/Co in the composites provide a short ion/electron transport path distance, high electronic conductivity, additional electrochemical active sites, and stable structural integrity. This viable strategy offers a good interaction between the CNS and ZCO, which translates to better electrochemical activity as an electrode material for energy storage devices. The CNS@ZCO-II composite with a higher CNS concentration shows an excellent electrochemical performance of approximately 1116.24 F g−1 at 0.35 A g−1 (compared to the pristine-ZCO and CNS@ZCO-I composite).

The development of clean sources of energy is important as the world is threatened by global warming and other serious consequences. The microbial fuel cell technology is considered as clean technology for the production of clean energy. The electrode materials used in the microbial fuel cell decides the major cost of MFCs. The use of novel antimony-tin based anode material and manganese dioxide as cathode material is demonstrated here. The present study discusses the synthesis and application of SnSb@rGO, Sb–SnSb@rGO and Sb–SnO2@rGO as anode electrode in three different microbial fuel cells for studying their performance, while using MnO2@rGO as cathode in all the setups. The synthesized materials were analysed for their structural characterisation by means of X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, field mission scanning electron microscopy. Performance analysis of all MFCs are carried out to obtain polarization curves, maximum power density, current density, COD removal percentage and substrate degradation percentage. The results indicate that among the three MFCs, The MFC with Sb–SnSb@rGO prepared with Zn dust showed higher performance.

Desulphurization of Ferronickel in the converters with oxygen is the most complex part of the technological process in the Drenas foundry. Sulphur in the ferronickel melting is mostly in the form of FeS, with a melting temperature of 1195oC, and it has tendency to dissolve indefinitely in liquid iron. Our objective is to determine the sulphur removal coefficient, as a key indicator of the desulphurization efficiency in the converter, by measuring the activity and concentration of sulphur and other elements in liquid Fe and melting. Determination of this coefficient is done according to the analytical method, while comparing the current process parameters with those of the new desulfurization methods, other indicators of the refining process are determined. The refining process and the effective conduct of the study depend on the XRD analysis database of metal and slag, and as well of the technological refining process analysis data. Research has shown that desulfurization efficiency is a function of the sulphur removal coefficient, respectively; metal composition, slag, oxygen activity, CaO/SiO2 ratio, sulphide capacity, fluidity, surface pressure, etc.). In addition to this coefficient, other indicators of refining process optimization are defined.

In a steel plant, basic oxygen furnace (BOF) is a method to convert liquid hot metal and steel scrap into steel with oxidizing action of oxygen blowing into the melt. A water-cooled lance is used for blowing of pure gaseous oxygen (> 99.5%) at high pressure and flow rate of 11–13 kg/cm2 and ~ 1000 Nm3/min, respectively. A failure of BOF lance head assembly occurred in one of the integrated steel plants. A small oxygen leak ignited near the flange and a significant portion of the oxygen pipe elbow was consumed. The failure analysis was carried out, and likely reasons for the failure were identified. During the BOF process, oxygen is blown at high velocity into molten, carbon-saturated hot metal as received from blast furnaces. Oxygen reacts with carbon to form carbon monoxide (CO) and carbon dioxide (CO2) gases, among other reactions. The occurrence of flames, metal spitting and post-combustion of CO gas generates high-temperature conditions that can damage the oxygen lance assembly. They can also cause changes in microstructure of the parent material (low-carbon-grade SS310S) of the elbow and weaken the material over a period of time. It was found that the presence of a minute puncture in the oxygen pipe line may, under thermodynamically favorable conditions, ignite the leaking oxygen. Such a minute leakage may have occurred due to failure of material, weld joint or detachable joint.

Noncovalent interactions are key determinants in both chemical and biological processes. Among such processes, the hydrophobic interactions play an eminent role in folding of proteins, nucleic acids, formation of membranes, protein-ligand recognition, etc.. Though this interaction is mediated through the aqueous solvent, the stability of the above biomolecules can be highly sensitive to any small external perturbations, such as temperature, pressure, pH, or even cosolvent additives, like, urea—a highly soluble small organic molecule utilized by various living organisms to regulate osmotic pressure. A plethora of detailed studies exist covering both experimental and theoretical regimes, to understand how urea modulates the stability of biological macromolecules. While experimentalists have been primarily focusing on the thermodynamic and kinetic aspects, theoretical modeling predominantly involves mechanistic information at the molecular level, calculating atomistic details applying the force field approach to the high level electronic details using the quantum mechanical methods. The review focuses mainly on examples with biological relevance, such as (1) urea-assisted protein unfolding, (2) urea-assisted RNA unfolding, (3) urea lesion interaction within damaged DNA, (4) urea conduction through membrane proteins, and (5) protein-ligand interactions those explicitly address the vitality of hydrophobic interactions involving exclusively the urea-aromatic moiety.

Sm3+ ions doped strontium lithium lead borate glasses (SLLB:Sm) were prepared using a conventional melt-quenching technique. The glasses were analyzed using X-ray diffractometry and Fourier transform infrared spectroscopy, optical absorption, fluorescence spectral analysis, and fluorescence lifetime decay. The Judd-Ofelt (J-O) parameters and radiative parameters of the SLLB:Sm10 glass (1.0 mol% Sm3+ ion-doped glass) were calculated using J-O theory. From the emission spectra, among all the synthesized glass, SLLB:Sm10 glass had the highest emission intensity for 4 G5/2 →6 H11/2 transition (610 nm). Emission parameters, such as stimulated emission cross-section and optical gain bandwidth, were calculated. For all concentrations of Sm3+ ions, the decay profile showed an exponential nature and decreased when the Sm3+ ion concentration was increased due to a concentration quenching effect. This result suggests that the synthesized SLLB:Sm10 glass could be used for application in high-density optical memory devices.

The optical activity of a metal nanocluster (NC) is induced either by an asymmetric arrangement of constituents or by a dissymmetric field of a chiral ligand layer. Herein, we unveil the origin of chirality in Ag29 NCs, which is attributed to the intrinsically chiral atomic arrangement. The X-ray crystal structure of a Ag29(BDT)12(TPP)4 NC (BDT: 1,3-benzenedithiol; TPP: triphenylphosphine) manifested the presence of intrinsic chirality in the outer shell capping the icosahedral achiral Ag13 core. The enantiomers of the Ag29(BDT)12(TPP)4 NC are separated by high-performance liquid chromatography (HPLC) using a chiral column for the first time, showing mirror-image circular dichroism (CD) spectra. The CD spectra are reproduced by time-dependent density functional theory (TDDFT) calculations based on enantiomeric Ag29 models with achiral 1,3-propanedithiolate ligands. The mechanism of chiral induction in the synthesis of Ag29(DHLA)12 (DHLA: α-dihydrolipoic acid) NCs with a chiral ligand system is further discussed with the aid of DFT calculations. The use of the enantiomeric DHLA ligand preferentially leads to a one-handed atomic arrangement which is more stable than the opposite one, inducing the enantiomeric excess in the population of intrinsically chiral Ag29 NCs with CD activity.

This paper presents a study on how body material properties affects the electrical characteristics of a Junctionless field effect transistor (JLFET). The study is performed by simulating a symmetric double gate JLFET on TCAD simulator for the materials- Silicon (Si), Germanium (Ge), Gallium Arsenide (GaAs) and Gallium Nitride (GaN). Simulations show that the use of compound materials (GaAs, GaN) in the body of JLFET results in better electrical characteristics compared to other element semiconductor (Si, Ge).

Free heme activates erythroblasts to express and secrete Placenta Growth Factor (PlGF), an angiogenic peptide of the VEGF family. High circulating levels of PlGF have been associated in experimental animals and in patients with sickle cell disease with echocardiographic markers of pulmonary hypertension, a life-limiting complication associated with more intense hemolysis. We now show that the mechanism of heme regulation of PlGF requires the contribution of the key antioxidant response regulator NRF2. Mimicking the effect of heme, the NRF2 agonist sulforaphane stimulates the PlGF transcript level nearly 30-fold in cultured human erythroblastoid cells. Heme and sulforaphane also induce transcripts for NRF2 itself, its partners MAFF and MAFG, and its competitor BACH1. Furthermore, heme induction of the PlGF transcript is significantly diminished by the NRF2 inhibitor brusatol and by siRNA knockdown of the NRF2 and/or MAFG transcription factors. Chromatin immunoprecipitation experiments show that heme induces NRF2 to bind directly to the PlGF promoter region. In complementary in vivo experiments, mice injected with heme show a significant increase in their plasma PlGF protein as early as 3 h after treatment. Our results reveal an important mechanism of PlGF regulation, adding to the growing literature that supports the pivotal importance of the NRF2 axis in the pathobiology of sickle cell disease.

Neodymium doped zinc sulphide (Nd: ZnS) thin films were coated on glass substrates at 450 °C through low cost nebulizer spray pyrolysis (NSP) method. Structure, morphology, opto-electrical characteristics of Nd doped ZnS films with various Nd doping concentrations (0%, 1, %, 3% and 5%) were studied. X-ray diffraction patterns revealed that all coated films were polycrystalline hexagonal structure with (102) as a preferential direction. SEM images showed smooth and uniform spherical grains without any cracks and pinholes. Topological view by AFM described the increasing of roughness of the film through doping concentration. EDAX and Elemental mapping images confirmed the presence of Zn, S and Nd without any other impurities. Raman spectra reveals that E1(LO), 2TO, 2LO and 3LO emission modes with corresponding to the wave number. PL spectra showed high intense visible and broad UV emission band at 463 nm and 397 nm, respectively. Thickness of the films increased with Nd doping concentration reflecting the reduction of transparency of the films from 86% to 78% for 0% and 5% of Nd. UV–Vis Spectrum was used to study the energy gap (Eg), dielectric constant(e), refractive index(n), and extinction coefficient (k) of the prepared films. Four-point probe method was used to calculate the activation energy of Nd: ZnS thin films from the graph drawn between ln (ρ) and (1/T).

Simple Summary The development of a rare cancer of the immune system (lymphoma) associated with breast implants has been increasingly reported around the world. It has been hypothesized that the cancer is triggered by inflammation from bacteria residing within the textured surface of these implants, transforming the lymphocytes of some genetically prone patients over many years. This study shows that bacteria rather than the implant itself can trigger activation and multiplication of these cancer cells in the laboratory, lending support that bacteria and their products play an important role in causation. The unique response of these cancer cells to bacterial antigen was dampened significantly in the presence of a Toll-like receptor 4 inhibitor peptide. This finding has significance for both cancer prevention and treatment. Abstract Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a distinct malignancy associated with textured breast implants. We investigated whether bacteria could trigger the activation and multiplication of BIA-ALCL cells in vitro. BIA-ALCL patient-derived BIA-ALCL tumor cells, BIA-ALCL cell lines, cutaneous ALCL cell lines, an immortal T-cell line (MT-4), and peripheral blood mononuclear cells (PBMC) from BIA-ALCL, capsular contracture, and primary augmentation patients were studied. Cells were subjected to various mitogenic stimulation assays including plant phytohemagglutinin (PHA), Gram-negative bacterial lipopolysaccharide (LPS), Staphylococcal superantigens enterotoxin A (SEA), toxic shock syndrome toxin-1 (TSST-1), or sterilized implant shells. Patient-derived BIA-ALCL tumor cells and BIA-ALCL cell lines showed a unique response to LPS stimulation. This response was dampened significantly in the presence of a Toll-like receptor 4 (TLR4) inhibitor peptide. In contrast, cutaneous ALCL cells, MT-4, and PBMC cells from all patients responded significantly more to PHA, SEA, and TSST-1 than to LPS. Breast implant shells of all surface grades alone did not produce a proliferative response of BIA-ALCL cells, indicating the breast implant does not act as a pro-inflammatory stimulant. These findings indicate a possible novel pathway for LPS to promote BIA-ALCL cell proliferation via a TLR4 receptor-mediated bacterial transformation of T-cells into malignancy.

Here we report the synthesis of an N-heterocyclic carbene (NHC)-stabilised phosphinidene oxide by the controlled oxygenation of a phosphinidene under ambient conditions. This compound can be further oxygenated to a phosphinidene dioxide. The stoichiometric reduction of a phosphinidene oxide with KC8 resembles the pinacol coupling reaction–the reduction of a carbonyl compound. We also looked at the stoichiometric oxidation of NHC-coordinated phosphinidene, phosphinidene oxide and phosphinidene dioxide with [NO][SbF6].

Synthetic ion channels are a promising technology in the medical and materials sciences because of their ability to conduct ions. Channels based on cyclodextrin, a cyclic oligomer of glucose, are of particular interest because of their nontoxicity and biocompatibility. Using molecular dynamics-based free energy calculations, this study identifies cyclodextrin channel types that are best suited to serve as synthetic ion channels. Free energy profiles show that the connectivity in the channel determines whether the channel is cation-selective or anion-selective. Furthermore, the energy barrier for ion transport is governed by the number of glucose molecules making up the cyclodextrin units of the channel. A detailed mechanism is proposed for ion transport through these channels. Findings from this study will aid in designing cyclodextrin-based channels that could be either cation-selective or anion-selective, by modifying the linkages of the channel or the number of glucose molecules in the cyclodextrin rings.

In drug discovery applications, high throughput virtual screening exercises are routinely performed to determine an initial set of candidate molecules referred to as “hits”. In such an experiment, each molecule from a large small-molecule drug library is evaluated in terms of physical properties such as the docking score against a target receptor. In real-life drug discovery experiments, drug libraries are extremely large but still there is only a minor representation of the essentially infinite chemical space, and evaluation of physical properties for each molecule in the library is not computationally feasible. In the current study, a novel Machine learning framework for Enhanced MolEcular Screening (MEMES) based on Bayesian optimization is proposed for efficient sampling of the chemical space. The proposed framework is demonstrated to identify 90% of the top-1000 molecules from a molecular library of size about 100 million, while calculating the docking score only for about 6% of the complete library. We believe that such a framework would tremendously help to reduce the computational effort in not only drug-discovery but also areas that require such high-throughput experiments., A novel machine learning framework based on Bayesian optimization for efficient sampling of chemical space. The framework is able to identify 90% of top-1000 hits by only sampling 6% of the complete dataset containing ∼100 million compounds.

Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (67Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma–mass spectrometry (LA-ICP-MS) methodology. Multiphoton microscopy with second harmonic generation imaging showed that 67ZnO NPs were retained on the surface or within the superficial layers of the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both the SC and VE relative to untreated skin, confirming that dissolved zinc species permeated across the SC into the VE as ionic Zn and significantly not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous 67Zn concentrations in the VE of 1.0 ± 0.3 μg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 μg/mL. Furthermore, their combined total zinc concentrations in the VE are much lower than the exogenous zinc concentration of 21 to 31 μg/mL causing VE cytotoxicity, as defined by the half-maximal inhibitory concentration of exogenous 67Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance.

The optical activity of a metal nanocluster (NC) is induced either by an asymmetric arrangement of constituents or by a dissymmetric field of a chiral ligand layer. Herein, we unveil the origin of chirality in Ag29 NCs, which is attributed to the intrinsically chiral atomic arrangement. The X-ray crystal structure of a Ag29(BDT)12(TPP)4 NC (BDT: 1,3-benzenedithiol; TPP: triphenylphosphine) manifested the presence of intrinsic chirality in the outer shell capping the icosahedral achiral Ag13 core. The enantiomers of the Ag29(BDT)12(TPP)4 NC are separated by high-performance liquid chromatography (HPLC) using a chiral column for the first time, showing mirror-image circular dichroism (CD) spectra. The CD spectra are reproduced by time-dependent density functional theory (TDDFT) calculations based on enantiomeric Ag29 models with achiral 1,3-propanedithiolate ligands. The mechanism of chiral induction in the synthesis of Ag29(DHLA)12 (DHLA: α-dihydrolipoic acid) NCs with a chiral ligand system is further discussed with the aid of DFT calculations. The use of the enantiomeric DHLA ligand preferentially leads to a one-handed atomic arrangement which is more stable than the opposite one, inducing the enantiomeric excess in the population of intrinsically chiral Ag29 NCs with CD activity., Enantioseparation of Ag29 nanoclusters with intrinsic chirality was performed by chiral HPLC, affording a pair of fractions with mirror image CD spectra.

In circulating fluidized bed combustion (CFBC) boilers, the method of feeding of limestone with fuel into the furnace gives high desulphurization efficiency and avoids the usage of pulverization equipment in the plants. Ca/S molar ratio and bed temperature play an important role in the process of sulphur capture. Generally, Ca/S ratio ranges between 2 and 6 and bed temperature is around 800–900 ​°C in the commercial CFBC boilers. Higher value of Ca/S ratio and optimum value of bed temperature provide higher desulphurization efficiency. The present work focuses on providing the stipulated value of Ca/S molar ratio (1–6), bed temperature (800oC–925 ​°C) which are required to achieve 95% sulphur capture efficiency for Indian lignite based CFBC boiler operating with 210MW steam parameters using simplified sulphur capture model. The work also shows the effect of Ca/S molar ratio and bed temperature on the values of sulphur emissions, reaction rate of sulphation, limestone feed rate and boiler efficiency for three lignite samples which are popularly available and used in commercial operations of Indian CFBC boilers.

Pure In2O3 and 6% Cr-doped In2O3 thin films were prepared on a silicon (Si) substrate by pulsed laser deposition technique. The obtained In2O3/In2O3:Cr thin films structural, morphological, optical, magnetic and gas sensing properties were briefly investigated. The X-ray diffraction results confirmed that the grown thin films are in single-phase cubic bixbyte structure with space group Ia-3. The SEM analysis showed the formation of agglomerated spherical shape morphology with the decreased average grain size for Cr doped In2O3 thin film compared to pure In2O3 film. It is observed that the Cr doped In2O3 thin film shows the lower band gap energy and that the corresponding transmittance is around 80%. The X-ray photoelectron spectroscopy measurements revealed that the presence of oxygen vacancy in the doped In2O3 film. These oxygen defects could play a significant role to enhance the sensing performance towards chemical species. In the magnetic hysteresis loop, it is clear that the prepared films confirm the ferromagnetic behaviour and the maximum saturation value of 39 emu/cc for Cr doped In2O3 film. NH3 gas sensing studies was also carried out at room temperature for both pure and Cr doped In2O3 films, and the obtained higher sensitivity is 182% for Cr doped In2O3, which is about nine times higher than for the pure In2O3 film due to the presence of defects on the doped film surface.

Energetically unfavorable Watson–Crick (WC)-like tautomeric forms of nucleobases are known to introduce spontaneous mutations, and contribute to replication, transcription, and translation errors. Recent NMR relaxation dispersion techniques were able to show that wobble (w) G•U mispair exists in equilibrium with the short-lived, low-population WC-like enolic tautomers. Presently, we have investigated the wG•U → WC-like enolic reaction pathway using various theoretical methods: quantum mechanics (QM), molecular dynamics (MD), and combined quantum mechanics/molecular mechanics (QM/MM). The previous studies on QM gas phase calculations were inconsistent with experimental data. We have also explored the environmental effects on the reaction energies by adding explicit water. While the QM-profile clearly becomes endoergic in the presence of water, the QM/MM-profile remains consistently endoergic in the presence and absence of water. Hence, by including microsolvation and QM/MM calculations, the experimental data can be explained. For the G•Uenol→ Genol•U pathway, the latter appears to be energetically more favorable throughout all computational models. This study can be considered as a benchmark of various computational models of wG•U to WC-like tautomerization pathways with and without the environmental effects, and may contribute on further studies of other mispairs as well.

An orb web's adhesive capture spiral is responsible for prey retention. This thread is formed of regularly spaced glue droplets supported by two flagelliform axial lines. Each glue droplet features a glycoprotein adhesive core covered by a hygroscopic aqueous layer, which also covers axial lines between the droplets, making the entire thread responsive to environmental humidity. We characterized the effect of relative humidity (RH) on ability of Argiope aurantia and Argiope trifasciata thread arrays to retain houseflies and characterize the effect of humidity on their droplet properties. Using these data and those of Araneus marmoreus from a previous study, we then develop a regression model that correlated glycoprotein and flagelliform fiber properties with prey retention time. The model selection process included newly determined, humidity‐specific Young's modulus and toughness values for the three species' glycoproteins. Argiope aurantia droplets are more hygroscopic than A. trifasciata droplets, causing the glycoprotein within A. aurantia droplets to become oversaturated at RH greater than 55% RH and their extension to decrease, whereas A. trifasciata droplet performance increases to 72% RH. This difference is reflected in species' prey retention times, with that of A. aurantia peaking at 55% RH and that of A. trifasciata at 72% RH. Fly retention time was explained by a regression model of five variables: glue droplet distribution, flagelliform fiber work of extension, glycoprotein volume, glycoprotein thickness, and glycoprotein Young's modulus. The material properties of both glycoprotein and flagelliform fibers appear to be phylogenetically constrained, whereas natural selection can more freely act on the amount of each material invested in a thread and on components of the thread's aqueous layer. Thus, it becomes easier to understand how natural selection can tune the performance of viscous capture threads by directing small changes in these components.

Undoped and rare earth Neodymium (Nd) doped cuprous oxide (Cu2O) thin films were prepared by electrodeposition method. The prepared film's structural, morphological, optical and photosensitive properties were analyzed by X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, ultra violet-visible and I-V measurements. The fabricated Cu2O:Nd films exhibited polycrystalline nature with cubic crystal system, and favorably grown along (111) orientation. Crystallite size was decreased from 56 nm to 30 nm with Nd concentrations. Raman spectrum confirmed the Cu2O phase of the prepared films. The morphological analysis showed pyramidal shaped particles for the undoped Cu2O thin film. The energy gap was reduced from 2.04 eV to 1.89 eV as Nd doping level was increased. From photoluminescence spectrum a high intense peak was observed at 619 nm which confirms the optical quality of Cu2O phase. The dielectric constant was increased by increasing the Nd doping concentration from 0 to 5%. In photosensitivity analysis an increase of photo response with respect to illuminated current was observed.

In the proposed research article, polymer nanocomposites on the basis of thermoset polymer resultant blends (epoxy/polyester) having wollastonite powder are prepared by high shear mixer (mechanical), followed by an ultra-sonicator for uniform dispersion of wollastonite particulates in the final blend matrix. Wide range percentages of modified wollastonite nano-particulates with 0, 1, 2, 3, 4 and 5 wt. % were incorporated into the epoxy/polyester blend matrix in order to evaluate the effect of nanofillers on nanophase morphological structure and to study material properties. Various thermal parameters of the nanocomposite were evaluated using thermogravimetric analysis and differential scanning calorimetry techniques. Further, the scanning electron microscopy images have been employed to know fractured surfaces of the titled compound. From the experimental data it was found that uniform miscibility of epoxy/polyester blend mix and homogenous dispersion of wollastonite nano particulates in the blend matrix was noticed. From the TGA studies, 8 % weight loss and 4 °C rise in decomposition temperature was observed with addition of 5 wt. % wollastonite when compared with the 0 wt. % wollastonite combination of epoxy/unsaturated polyester resin blend. DSC results further revealed that the modified wollastonite nanoparticles is major responsible for the glass transition temperature (Tg) of the nanocomposites.

Inappropriate and uncontrolled use of antibiotics results in the emergence of antibiotic resistance, thereby threatening the present clinical regimens to treat infectious diseases. Therefore, new antimicrobial agents that can prevent bacteria from developing drug resistance are urgently needed. Selective disruption of bacterial membranes is the most effective strategy for combating microbial infections as accumulation of genetic mutations will not allow for the emergence of drug resistance against these antimicrobials. In this work, we tested cholic acid (CA) derived amphiphiles tethered with different alkyl chains for their ability to combat Gram-positive bacterial infections. In-depth biophysical and biomolecular simulation studies suggested that the amphiphile with a hexyl chain (6) executes more effective interactions with Gram-positive bacterial membranes as compared to other hydrophobic counterparts. Amphiphile 6 is effective against multidrug resistant Gram-positive bacterial strains as well and does not allow the adherence of S. aureus on amphiphile 6 coated catheters implanted in mice. Further, treatment of wound infections with amphiphile 6 clears the bacterial infections. Therefore, the current study presents strategic guidelines in design and development of CA-derived membrane-targeting antimicrobials for Gram-positive bacterial infections.

Thin films of neodymium (Nd) doped zinc oxide (NZO) were coated onto glass substrates at 400 °C by nebulized spray pyrolysis using different doping weight percentage (wt%) of Nd. The prepared films were exhibited in hexagonal structure of polycrystalline nature along with (002) preferential orientation. Morphological properties and elemental compositions were performed by scanning electron microscopy and energy dispersive by X-ray, respectively. Tauc’s plot discovered the optical energy band gap of 3.17 eV for 5 wt% Nd doped NZO film. PL profiles depicted a solid green emission peak at around 680 nm at room temperature. Optical constants such as refractive indices, dielectric constants, carrier concentration and plasma frequency were evaluated for NZO through optical approximation route. Hall mobility and carrier concentrations were enhanced with rise of Nd doping wt%. A drastic change in the resistivity was observed due to incorporation of Nd dopant and it has evidently demonstrated in detail.

Demand rises in a worldwide series of the new materials at national and international level. The metal matrix nano-composites are extremely beneficial in several applications such as aerospace, automobile, armed forces, and other commercial applications due to lightweight and cost-effective. In the present study, three various hybrid compositions, namely nano-Al2O3 (20–30 nm), nano-SiC (50 nm), and Mg 1 wt% (fixed), were used as reinforcement materials. Magnesium is to enhance the wettability of Al2O3 and SiC particles in the Al matrix. The compositions are executed at 1.0, 2.0, 3.0, and also 4.0 weight % of nano-Al2O3 and nano-SiC. The cast samplings undertake the tests like heat treatment, microstructural examination, density, tensile, hardness, impact, SEM, EDAX, and XRD analysis. SEM images subject that the nanoparticles relatively disperse as well as attain fine grain microstructure in the matrix. The results reveal that the reinforcement of nanoparticles in Al 7075 matrix substantially increases the mechanical behaviour when compared to base metal.