Quantitative Mechanistic Modeling in Support of Pharmacological Therapeutics Development in Immuno-Oncology

Following the approval, in recent years, of the first immune checkpoint inhibitor, there has been an explosion in the development of immuno-modulating pharmacological modalities for the treatment of various cancers. From the discovery phase to late-stage clinical testing and regulatory approval, challenges in the development of immuno-oncology (IO) drugs are multi-fold and complex. In the preclinical setting, the multiplicity of potential drug targets around immune checkpoints, the growing list of immuno-modulatory molecular and cellular forces in the tumor microenvironment—with additional opportunities for IO drug targets, the emergence of exploratory biomarkers, and the unleashed potential of modality combinations all have necessitated the development of quantitative, mechanistically-oriented systems models which incorporate key biology and patho-physiology aspects of immuno-oncology and the pharmacokinetics of IO-modulating agents. In the clinical setting, the qualification of surrogate biomarkers predictive of IO treatment efficacy or outcome, and the corresponding optimization of IO trial design have become major challenges. This mini-review focuses on the evolution and state-of-the-art of quantitative systems models describing the tumor vs. immune system interplay, and their merging with quantitative pharmacology models of IO-modulating agents, as companion tools to support the addressing of these challenges

Host range breadth of bacteriophages

The literature review aims at summarizing quantitative data on spotting and plaquing bacteriophage host ranges

Formation of SnO and SnO2 phases during the annealing of SnO(x) films obtained by molecular beam epitaxy

SnO and SnO2 films were obtained on the SiO2 surface by the molecular-beam epitaxy method. The initial film

Evaluation of the Efficiency of Generation of Terahertz Surface Plasmon Polaritons by the End-Fire Coupling Technique

One of the most important problems in the plasmonics of the terahertz (THz) range, which is actively developing now, is the efficient generation of surface plasmon polaritons (SPPs). The simplest and most promising technological technique of photon excitation of THz SPPs is through diffraction of radiation on the edge of the conducting surface of the sample (the end-fire coupling technique). In this paper, we experimentally evaluated the efficiency of the generation of monochromatic THz SPPs (λ0 = 141 μm) by this method with a sample in the form of a cylindrical segment, the convex surface of which has a gold layer coated by zinc sulfide (ZnS) with thickness d = 0–2 µm. Such configuration of the surface supporting the SPPs not only shields the detector from parasitic bulk waves arising during diffraction but also enables one to change the distribution of the SPP field in the air by varying the coating layer thickness d. On an uncoated gold surface, the SPP generation efficiency was η ≈ 20%. In the presence of a ZnS layer on the gold, the SPP generation efficiency gradually increased with d, reached the maximum (ηmax ≈ 60%) at d ≈ 1 μm, and then gradually decreased. Theoretical analysis showed that the efficiency of the SPP generation can be raised up to 80% due to the selection of an optimal SPP field profile via variation of the thickness of the dielectric layer on the metal surface, as well as with optimal incidence of the focused radiation on the edge of the sample

Lack of allosterically controlled intramolecular transfer of nitric oxide from the heme to cysteine in the β subunit of hemoglobin

The SNO-Hb hypothesis holds that heme-bound nitric oxide (NO) present in the β subunits of T-state hemoglobin (Hb) will be transferred to the β-93 cysteine upon conversion to R-state Hb, thereby forming SNO-Hb. A deficiency in the ability of Hb to facilitate this intramolecular transfer has recently been purported to play a role in pulmonary hypertension and sickle cell disease. We prepared deoxygenated Hb samples with small amounts of heme-bound NO and then oxygenated the samples. Electron paramagnetic resonance (EPR) spectroscopy was used to (1) determine the concentration of iron nitrosyl Hb (Fe-NO Hb), (2) show that the NO is evenly distributed among α and β subunits, and (3) show that the Hb undergoes a change in its quaternary state (T to R) upon oxygenation. We did not observe a decrease in the concentration of Fe-NO Hb on oxygenation, which is inconsistent with the prediction of the SNO-Hb hypothesis

Morphology, structure, and optical properties of SnO (x) films

The paper presents the morphological, structural, and optical properties of nanostructured SnO (x) film

The Influence of Argon Cluster Ion Bombardment on the Characteristics of AlN Films on Glass-Ceramics and Si Substrates

In this paper, the influence of surface modification on the characteristics and properties of AlN thin films on Si and glass-ceramics substrates is investigated. The surface modification was made at various parameters of argon cluster ions. By using XRD and Raman spectroscopy, it was shown that the obtained AlN films have a hexagonal structure with a characteristic direction of texturing along the c axis and slight deviations from it. A comparison of the AlN surface morphology obtained by atomic force microscopy before and after cluster processing was demonstrated. This demonstrated that the cluster ions with low energy per atom (E/N = 10 eV/atom) have a high efficiency of surface smoothing. A decrease in the intensity of the Raman peaks and an increase in their full-width after bombardment with cluster ions were found, which may be caused by a change in the physicochemical state of the surface. The optical properties, the quality of the boundaries, and the distribution map of the thickness of the functional layer of AlN were investigated by the methods of spectral and spatial resolution ellipsometry. By using the cross-sectional SEM, the direction of crystallite texturing was demonstrated. The influence of argon cluster ion bombardment on the stoichiometry of samples was analyzed by EDX spectroscopy. The results obtained demonstrate the efficiency of the cluster ion smoothing of polycrystalline thin films for microelectronics, particularly when creating surface acoustic wave resonators

Effect of annealing temperature on the morphology, structure, and optical properties of nanostructured SnO(x) films

Fabrication and characterization of titanium dioxide (TiO2) thin film on Al/TiO2/SiO2/p-Si MIS structure for the study of morphology, optical and electrical properties were reported. A transparent and high crystallinity of TiO2 thin films were prepared at room temperature (~25 °C) by sol–gel route. TiO2 sol suspension were prepared at molar ratio of TTIP:EtOH:AA = 2:15:1 using titanium tetra-isopropoxide (TTIP) and a mixture of absolute ethanol (EtOH) and acetic acid (AA) which used as a precursor and catalyst for the peptization, respectively. The TiO2 thin films were deposited on a thermally grown SiO2 layer of p-type silicon (100) substrates and were thermally treated at different annealing temperatures of 300, 500, 700 and 900 °C. For study of optical properties, the TiO2 thin films were deposited on a glass slides substrate and were annealed from 200 to 700 °C. The XRD results show that the presence of an amorphous TiO2 phases were transformed into the polycrystalline (anatase or rutile) with good crystallinity after treated at higher annealing temperatures. Besides, the surface roughness of TiO2 thin films increased with increasing annealing temperatures. In addition, the resistivity of the thin films decreased from 2.5751E+8 to 6.714E+7 Ω cm with the increasing temperatures. Moreover, the optical absorbance of TiO2 thin films exhibited high UV–visible light absorption with band gap energy shifted to the higher wavelength (low energy photons). The band gap energy (Eg) of the films decreased from 3.79 to 3.16 eV and from 3.95 to 3.75 eV significantly for direct band allowed and indirect band allowed, respectively, with the increasing annealing temperatures