Reports of NAS RA

Cancer type specific copy number variants are identical over species borders

Thomas Liehr — Mon, 06 Jul 2026 00:00:00 +0000

Over the past two decades, we have studied dozens of murine and a few rat-derived tumor cell lines. While these cell lines are commonly used as models for human cancer, their cytogenetic and genetic properties are not fully understood. Therefore, we characterized approximately 40 rodent cancer cell lines using molecular cytogenetics, including multicolor fluorescence in situ hybridization and array-comparative genomic hybridization. We then in silico translated the observed acquired gains and losses of chromosomal regions into the human genome. During these studies, we found that rodent cancer cell lines carried chromosomal imbalances similar to those observed in human cancer cells. In this review, we discuss the cell lines studied, the percentage of gains and losses that agreed with the corresponding human cancer type, and the human cancer subtypes for which each cell line can serve as a suitable model. Additionally, we discuss the fact that polyploidy can only be reliably accessed by cytogenetics and that male cell lines tend to lose their Y chromosome. Overall, the reviewed findings highlight the need for an in-depth cytogenomic characterization before using a cell line in research. Furthermore, the data support the idea that copy number changes are more important than point mutations, at least in advanced tumors, as they are similar across species boundaries.

Overvoltage Elimination of Dual-Branch Series–Parallel Charge Pumps with Thin Oxide Transistors

Vazgen Melikyan, Roman Ivanyan — Thu, 04 Jun 2026 00:00:00 +0000

Integrated circuits increasingly rely on on-chip generation of voltage levels beyond the nominal supply. Charge pumps provide this functionality using capacitors and switches, but their boosted internal nodes raise reliability concerns in scaled CMOS technologies, especially in processes offering only thin-oxide devices. Prior studies have shown that aging mechanisms such as bias temperature instability can noticeably alter the output voltage and startup behavior of conventional series-parallel charge pumps. This paper presents an aging-aware series–parallel voltage doubler that mitigates overstress at critical output nodes while preserving the intended voltage-boost operation. The circuit is sized to match the fresh-state characteristics of the reference design, enabling a fair comparison. Simulation results under long-term BTI stress confirm improved stability of the charge-pump behavior with reduced aging-induced drift.

Polyiodides of L-ornithine. Discovery of a symmetric (L-Orn(H)-H-L-OrnH) (3+)-cation

Tue, 30 Jun 2026 00:00:00 +0000

Two polyiodides of l-ornithine, (l-OrnH₂)(I₃)(I)(I₂) (I) and (l-Orn(H)-H-l-OrnH)(I₃)₃·4H₂O (II) have been synthesized and characterized structurally, by IR, Raman and UV-Vis spectroscopy. Electronic structures of both were determined by quantum chemical calculation based on their structures and bandgaps were measured experimentally as well. Salt (I) is triclinic, space group P1 with two formula units in the unit cell, salt (II) crystallizes in the monoclinic space group C2 with half of formula unit in the asymmetric unit. A symmetric dimeric cation (l-Orn(H)-H-l-OrnH) was observed in the structure of (II) for the first time.

Systematic Analysis of the HIV-1 Protease Active-Site Conformational Space Across 690 Crystal Structures

Hamlet Khachatryan — Tue, 16 Jun 2026 00:00:00 +0000

Human Immunodeficiency Virus-1 protease (HIV-1 PR) is among the most extensively studied drug targets in the Protein Data Bank (PDB), with more than 600 structural models predominantly derived by X-ray crystallography. This study presents a comprehensive analysis of the binding-site conformational space across the available structural record: 690 crystal structures deposited in the PDB with ≥90% sequence identity and resolution better than or equal to 2.50 Å, of which 684 were successfully featurized by pipeline. The structural dataset covers wild-type enzyme, crystallographic stabilization mutants, drug-resistant variants, and 452 distinct inhibitor binders. Each binding site was featurized as a volume-filling point cloud with six descriptors (electrostatic potential, lipophilicity, and pharmacophoric features) and represented as a geodesic distance matrix with further embedding in spectral distance space. Affinity propagation clustered all pockets into 16 discrete conformational states, with four dominant states accounting for 85% of all structures. The chemical space of the 452 extracted inhibitors is largely continuous, and its partitioning does not correspond to the receptor's conformational landscape; yet the molecular weight of binders correlates with cavity volume: heavier inhibitors disproportionately populate the largest closed-flap state, while lighter molecules favour a distinct, tighter binding envelope. This analysis provides a structural basis and insights for ensemble-based virtual screening, de novo generation of inhibitors, and the systematic interpretation of evidenced structure–ligand data across the HIV-1 PR inhibitor landscape.