Fabrication and Electrochemical Properties of Epitaxial Samarium‐Doped Ceria Films on SrTiO3‐Buffered MgO Substrates

Thin films of samarium‐oxide‐doped (20 mol%) ceria (SDC) are grown by pulsed‐laser deposition (PLD) on (001) MgO single‐crystal substrates. SrTiO₃ (STO) prepared by PLD is used as a buffer layer on the MgO substrates to enable epitaxial growth of the fluorite‐structured SDC film; the STO layer provides a proper crystalline match between SDC and MgO, resulting in highly crystalline, epitaxial SDC films grown in the (001) orientation. Film conductivity is evaluated by electrochemical impedance spectroscopy measurements, which are performed at various temperatures (400–775 °C) in a wide range of oxygen partial pressure (pO₂) values (10^?25?1 atm) in order to separate ionic and electronic conductivity contributions. At 700 °C, SDC/STO films on (100) MgO exhibit a dominant ionic conductivity of about 7 × 10^?2 S cm^?1, down to pO₂ values of about 10^?15 atm. The absence of grain boundaries make the SDC/STO/MgO heterostructures stable to oxidation‐reduction cycles at high temperatures, in contrast to that observed for the more disordered SDC/STO films, which degraded after hydrogen exposure.     

Development of antiviral fusion inhibitors: short modified peptides derived from the transmembrane glycoprotein of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a naturally occurring pathogen that causes an AIDS-like syndrome in domestic cats and is a valuable model system by which criteria for antiviral vaccines and drugs development can be tested. The cell-entry step of the lentivirus life cycle is regarded as a promising target for the development of new generation inhibitors. We have previously described potent in vitro anti-FIV activity associated with a synthetic octapeptide, termed C8 (Ac-Trp-Glu-Asp-Trp-Val-Gly-Trp-Ile-NH2), containing the Trp-rich motif of FIV transmembrane glycoprotein, which shares a common structural framework with the corresponding molecule of HIV and appears to play a similar role in cell entry. In this report, in an attempt to develop simpler potential fusion inhibitors to be tested in vivo, we describe further studies focused on synthetic peptide analogues of C8. Since C8 inhibitory activity is dependent upon the Trp motif, we systematically replaced these residues with bulky and/or aromatic natural and unnatural amino acids, in order to develop a rational structure-activity relationship. Furthermore, the amino acids located between the Trp residues, which are not crucial for inhibitory activity, were replaced by simple alkyl spacers of appropriate length. Design, NMR structural analysis, in vitro anti-FIV activity in lymphoid cell cultures, and serum stability of these new analogues are reported. The final results indicate that a simpler hexapeptide (Ac-Nal2-Ape-Nal2-Ape-Nal2-Ile-NH2; Nal2 = 3-naphthalen-2-yl-L-alanine, Ape = 5-aminopentanoic acid), almost entirely made up of unnatural amino acid residues, has markedly increased enzymatic stability, while maintaining strong antiviral potency in vitro.     

A modified phasor approach for analyzing time-gated fluorescence lifetime images

Fluorescence lifetime imaging is a versatile tool that permits mapping the biochemical environment in the cell. Among various fluorescence lifetime imaging techniques, time-correlated single photon counting and time-gating methods have been demonstrated to be very efficient and robust for the imaging of biological specimens. Recently, the phasor representation of lifetime images became popular because it provides an intuitive graphical view of the fluorescence lifetime content of the images and, when used for global analysis, significantly improves the overall S/N of lifetime analysis. Compared to time-correlated single photon counting, time gating methods can provide higher count rates (～10 MHz) but at the cost of truncating and under sampling the decay curve due to the limited number of gates commonly used. These limitations also complicate the implementation of the phasor analysis for time-gated data. In this work, we propose and validate a theoretical framework that overcomes these problems. This modified approach is tested on both simulated lifetime images and on cells. We demonstrate that this method is able to retrieve two lifetimes from time gating data that cannot be resolved using standard (non-global) fitting techniques. The new approach increases the information that can be obtained from typical measurements and simplifies the analysis of fluorescence lifetime imaging data.     

Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolo-Pyrimidinones Tethered with Hydrazide-Hydrazones

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds.     

Towards Quantitative and Standardized Serological and Neutralization Assays for COVID-19

Quantitative and robust serology assays are critical measurements underpinning global COVID-19 response to diagnostic, surveillance, and vaccine development. Here, we report a proof-of-concept approach for the development of quantitative, multiplexed flow cytometry-based serological and neutralization assays. The serology assays test the IgG and IgM against both the full-length spike antigens and the receptor binding domain (RBD) of the spike antigen. Benchmarking against an RBD-specific SARS-CoV IgG reference standard, the anti-SARS-CoV-2 RBD antibody titer was quantified in the range of 37.6 µg/mL to 31.0 ng/mL. The quantitative assays are highly specific with no correlative cross-reactivity with the spike proteins of MERS, SARS1, OC43 and HKU1 viruses. We further demonstrated good correlation between anti-RBD antibody titers and neutralizing antibody titers. The suite of serology and neutralization assays help to improve measurement confidence and are complementary and foundational for clinical and epidemiologic studies.     

Low-temperature synthesis of bismuth titanate by modified citrate amorphous method

Bismuth titanate is a lead-free piezoelectric ceramic with outstanding properties that strictly depend on the composition and microstructure. However, bismuth-based materials are difficult to synthesize due to bismuth volatilisation that causes secondary phases and stoichiometry deviations. In this work, we propose a low-temperature chemical route, i.e. a modified amorphous citrate method, that allows a reduction of thermal treatment temperature, when compared with solid-state or other chemical routes, to obtain single-phase bismuth titanate samples. Single-phase powders with particle size under 300 nm are produced by calcination at 700 °C, and prepared into homogeneous dense pellets (density above 95%), with only isolated pores. The pellets show two distinctive features in the electrical behaviours directly associated with their mica-like microstructure: planar oriented boundaries are responsible for oxygen conduction, while the bulk is dominated by electronic conductivity. The samples show a high dielectric constant, around 200 at room temperature, while maintaining a low loss factor. The pellets also achieved a maximum polarisation of 5.85 μC/cm² and an inverse piezoelectric coefficient of 7.4 pm/V. The dielectric and piezoelectric properties obtained are comparable or superior to the state-of-the-art.     

Indole-3-Glycerol Phosphate Synthase From Mycobacterium tuberculosis: A Potential New Drug Target

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis, affects millions of people worldwide. Several TB drugs have lost efficacy due to emerging drug resistance and new anti-TB targets are needed. Recent research suggests that indole-3-glycerol phosphate synthase (IGPS) in M. tuberculosis (MtIGPS) could be such a target. IGPS is a (β/α)₈-barrel enzyme that catalyzes the conversion of 1-(o-carboxyphenylamino)-1-deoxyribulose 5’-phosphate (CdRP) into indole-glycerol-phosphate (IGP) in the bacterial tryptophan biosynthetic pathway. M. tuberculosis over expresses the tryptophan pathway genes during an immune response and inhibition of MtIGPS allows CD4 T-cells to more effectively fight against M. tuberculosis. Here we review the published data on MtIGPS expression, kinetics, mechanism, and inhibition. We also discuss MtIGPS crystal structures and compare them to other IGPS structures to reveal potential structure-function relationships of interest for the purposes of drug design and biocatalyst engineering.     

Sintering of Multilayered Porous Structures: Part II–Experiments and Model Applications

Experimental analyses of shrinkage and distortion kinetics during sintering of bilayered porous and dense gadolinium‐doped ceria Ce_0.9Gd_0.1O_1.95?δ structures are carried out, and compared with the theoretical models developed in Part I of this work. A novel approach is developed for the determination of the shear viscosities ratio of the layer fully dense materials. This original technique enables the derivation of all the input parameters for the bilayer sintering modeling from one set of optical dilatometry measurements, including the conversion between real and specific times of sintering, the layers’ relative sintering intensity, and the shear viscosities ratio of the layer fully dense materials. These optical dilatometry measurements are conducted simultaneously for each individual layer and for a symmetric trilayered porous structure based on the two layers utilized in the bilayered system. The obtained modeling predictions indicate satisfactory agreement with the results of sintering of a bilayered cerium–gadolinium oxide system in terms of distortion and shrinkage kinetics.     

Inverting High Spectral Resolution Aerosol Optical Depth to Determine the Size Distribution of Atmospheric Aerosol

Measurements of aerosol optical depth are presented in the spectral interval 0.40–1.10 μm, which includes the most transparent region of the solar spectrum and the near infrared. The measurements were obtained by a grating spectrometer with a resolution ≈ 0.5 nm during the 1994 summer season at a mountain site (about 850 m above sea level) in the South of Italy. Spectral regions free from gas absorption features have been singled out and used to retrieve the aerosol columnar size distribution. Inversions have been performed by using the Phillips-Twomey inversion method along with a χ² criterion which allows one to choose a suitable value for the regularization parameter. The result of the inversions are presented in the particle radius range 0.1 ÷ 3 μm and indicate the presence of a bimodal aerosol with the second mode radius at about 1.0 μm undergoing transformations which are well correlated with relative humidity.