Emergent phenomena driven by electronic reconstructions in oxide heterostructures have been intensively discussed. However, the role of these phenomena in shaping the electronic properties in van der Waals heterointerfaces has hitherto not been established. By reducing the material thickness and forming a heterointerface, we find two types of charge-ordering transitions in monolayer VSe on graphene substrates. Angle-resolved photoemission spectroscopy (ARPES) uncovers that Fermi-surface nesting becomes perfect in ML VSe. Renormalization-group analysis confirms that imperfect nesting in three dimensions universally flows into perfect nesting in two dimensions. As a result, the charge-density wave-transition temperature is dramatically enhanced to a value of 350 K compared to the 105 K in bulk VSe. More interestingly, ARPES and scanning tunneling microscopy measurements confirm an unexpected metal-insulator transition at 135 K that is driven by lattice distortions. The heterointerface plays an important role in driving this novel metal-insulator transition in the family of monolayer transition-metal dichalcogenides.
Application of foreign clinical data across geographic regions can accelerate drug development. Drug disposition can be variable, and identification of factors influencing responsible pharmacokinetic/pharmacogenomic approaches could facilitate the universal application of foreign data and reduce the total amount of phase III clinical trials evaluating risks in different populations. Our objective was to establish and compare genotype (major cytochrome P450 (CYP) enzymes)/phenotype associations for Japanese (native and first- and third-generation Japanese living abroad), Caucasian, Chinese, and Korean populations using a standard drug panel. The mean metabolic ratios (MRs) for the four ethnic groups were similar except for a lower activity of CYP2D6 in Caucasians and CYP2C19 in Asians. Genotype, not ethnicity, impacted the MR for CYP2C9, CYP2C19, and CYP2D6; neither affected CYP1A2, CYP2E1, and CYP3A4/5 activities. We conclude that equivalent plasma drug concentrations and metabolic profiles can be expected for native Japanese, first- and third-generation Japanese, Koreans, and Chinese for compounds handled through these six CYP enzymes.
Articles you may be interested inMagnetic field role on the structure and optical response of photonic crystals based on ferrofluids containing Co0.25Zn0.75Fe2O4 nanoparticles Magnetic field dependant backscattering of light in water based ferrofluid containing polymer covered Fe3O4 nanoparticles J. Appl. Phys. 113, 054902 (2013); 10.1063/1.4789970 Particle blocking and carrier fluid freezing effects on the magnetic properties of Fe 3 O 4 -based ferrofluids J. Appl. Phys. 105, 07B511 (2009); 10.1063/1.3068461 X-ray diffraction and Mössbauer studies of structural changes and L1 0 ordering kinetics during annealing of polycrystalline Fe 51 Pt 49 thin filmsThe patterns of kerosene-based ferrofluid films in applied parallel and perpendicular magnetic fields were studied. The time dependence of quasiperiodic chains in a parallel magnetic field, the perfect hexagonal crystal structure in a weaker perpendicular field, and the labyrinthine pattern in a stronger perpendicular field were observed. The Fe 3 O 4 kerosene-based ferrofluids that we used in this study were synthesized by the coprecipitation method. As the parallel external magnetic field was applied to a ferrofluid film, the ordered quasiperiodic chains were obtained. On the other hand, the initial nonequilibrium disordered quantum columns were formed in an applied perpendicular magnetic field, and an equilibrium hexagonal structure with columns occupying its vortices was formed after two hours. The distance between these columns decreases as the strength of the applied magnetic field increases, and hence, the patterns change gradually from the hexagonal structure to a labyrinthine pattern with the strength of the perpendicular field above a critical value. Thus, a phase transition exists in the ferrofluid film system as the field strength increases.
This study aimed to evaluate endogenous metabolic markers of hepatic cytochrome P450 (CYP)3A activity in healthy subjects using a metabolomics approach. Twenty-four subjects received the following medication during the following three study periods: 1 mg of i.v. midazolam alone (control phase), 1 mg of i.v. midazolam after 4 days of pretreatment with 400 mg of ketoconazole once daily (CYP3A-inhibited phase), and 2.5 mg of i.v. midazolam after 10 days of pretreatment with 600 mg of rifampicin once daily (CYP3A-induced phase). During each study period, 24 h before and after the administration of midazolam, urine samples were collected at 12-h intervals for metabolomic analyses. We derived an equation to predict midazolam clearance (CL) based on several of these markers. We demonstrated that a combination of the concentrations and ratios of several endogenous metabolites and the CYP3A5*3 genotype is a reliable predictive marker of hepatic CYP3A activity as assessed by i.v. administration of midazolam.
Phenotypic differences in drug responses have been associated with known pharmacogenomic loci, but many remain to be characterized. Therefore, we developed next-generation sequencing (NGS) panels to enable broad and unbiased inspection of genes that are involved in pharmacokinetics (PKs) and pharmacodynamics (PDs). These panels feature repetitively optimized probes to capture up to 114 PK/PD-related genes with high coverage (99.6%) and accuracy (99.9%). Sequencing of a Korean cohort (n = 376) with the panels enabled profiling of actionable variants as well as rare variants of unknown functional consequences. Notably, variants that occurred at low frequency were enriched with likely protein-damaging variants and previously unreported variants. Furthermore, in vitro evaluation of four pharmacogenes, including cytochrome P450 2C19 (CYP2C19), confirmed that many of these rare variants have considerable functional impact. The present study suggests that targeted NGS panels are readily applicable platforms to facilitate comprehensive profiling of pharmacogenes, including common but also rare variants that warrant screening for personalized medicine.
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