PD-L1 Inhibitors: Different Classes,Activities, and Mechanisms of Action

Targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) interaction has become an established strategy for cancer immunotherapy. Although hundreds of small-molecule, peptide, and peptidomimetic inhibitors have been proposed in recent years, only a limited number of drug candidates show good PD-1/PD-L1 blocking activity in cell-based assays. In this article, we compare representative molecules from different classes in terms of their PD-1/PD-L1 dissociation capacity measured by HTRF and in vitro bioactivity determined by the immune checkpoint blockade (ICB) co-culture assay. We point to recent discoveries that underscore important differences in the mechanisms of action of these molecules and also indicate one principal feature that needs to be considered, which is the eventual human PD-L1 specificity.     

Functional Studies of Plant Latex as a Rich Source of Bioactive Compounds: Focus on Proteins and Alkaloids

Latex, a sticky emulsion produced by specialized cells called laticifers, is a crucial part of a plant’s defense system against herbivory and pathogens. It consists of a broad spectrum of active compounds, which are beneficial not only for plants, but for human health as well, enough to mention the use of morphine or codeine from poppy latex. Here, we reviewed latex’s general role in plant physiology and the significance of particular compounds (alkaloids and proteins) to its defense system with the example of Chelidonium majus L. from the poppy family. We further attempt to present latex chemicals used so far in medicine and then focus on functional studies of proteins and other compounds with potential pharmacological activities using modern techniques such as CRISPR/Cas9 gene editing. Despite the centuries-old tradition of using latex-bearing plants in therapies, there are still a lot of promising molecules waiting to be explored.     

Coherent-interface-induced strain in large lattice-mismatched materials:A new approach for modeling Raman shift

Strain engineering as one of the most powerful techniques for tuning optical and electronic properties of Ⅲ-nitrides requires reliable methods for strain invest...     

[ecosistema urbano]

Polish architecture tutors and critics Roman Rutkowski and Lukasz Wojciechowski identify a new kind of architecture in [ecosistema urbano]'s ingenious temporary tower pavilions for a sterile new housing estate in Madrid. Contributing power to the local electricity grid, these towers are explicitly designed to provide shelter from the unmediated heat of the harsh external environment through their cooling effect and in so doing to stimulate communal activities and events. Copyright © 2009 John Wiley & Sons, Ltd.     

Enhancing near-infrared avalanche photodiode performance by femtosecond laser microstructuring

A processing technique using femtosecond laser pulses to microstructure the surface of a silicon avalanche photodiode (APD) has been used to enhance its near-infrared (near-IR) response. Experiments were performed on a series of APDs and APD arrays using various structuring parameters and poststructuring annealing sequences. Following thermal annealing, we were able to fabricate APD arrays with quantum efficiencies as high as 58% at 1064 nm without degradation of their noise or gain performance. Experimental results provided evidence to suggest that the improvement in charge collection is a result of increased absorption in the near-IR.     

Crystal structure and lattice defects of La<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>MnO<Subscript>3 + δ</Subscript>

We report the synthesis of polycrystalline La _x MnO_{3 + δ} (x = 0.815, 0.90, 0.94, 0.97, 1.0) samples and their crystal structure at 300 K. All of the samples are single-phase and have an orthorhombically distorted (Pnma) perovskite structure. Also possible is that some of the samples have a rhombohedrally distorted structure. The unit-cell parameters of La_0.90MnO₃ differ most significantly from those of the x = 1.0 material. We have assessed the structural imperfection of the samples (cation vacancy concentration) and proposed overall chemical formulas of the manganites that take into account structural defects. Comparison of the X-ray and measured (hydrostatic weighing) densities of the samples demonstrates that their relative density increases with decreasing lanthanum content.     

Carbon-centered radicals in γ-irradiated bone substituting biomaterials based on hydroxyapatite

Gamma irradiated synthetic hydroxyapatite, bone substituting materials NanoBone(?) and HA Biocer were examined using EPR spectroscopy and compared with powdered human compact bone. In every case, radiation-induced carbon centered radicals were recorded, but their molecular structures and concentrations differed. In compact bone and synthetic hydroxyapatite the main signal assigned to the CO(2) (-) anion radical was stable, whereas the signal due to the CO(3) (3-) radical dominated in NanoBone(?) and HA Biocer just after irradiation. However, after a few days of storage of these samples, also a CO(2) (-) signal was recorded. The EPR study of irradiated compact bone and the synthetic graft materials suggest that their microscopic structures are different. In FT-IR spectra of NanoBone(?), HA Biocer and synthetic hydroxyapatite the HPO(4) (2-) and CO(3) (2-) in B-site groups are detected, whereas in compact bone signals due to collagen dominate.     

Elastic properties of Li<Subscript>2</Subscript>Zn<Subscript>2</Subscript>(MoO<Subscript>4</Subscript>)<Subscript>3</Subscript> single crystals

The complete elastic modulus matrix of Li₂Zn₂(MoO₄)₃ single crystals has been measured for the first time. The sound velocity has been measured in different directions of the crystals by a pulse-phase method. The measurement results have been used to calculate elastic moduli. The sound velocity has been calculated in the three main crystallographic planes of the crystals.