The Comparison of Machine Learning and Mechanistic In Vitro-In Vivo Extrapolation Models for the Prediction of Human Intrinsic Clearance.

Accurate prediction of human pharmacokinetics (PK) remains one of the key objectives of drug metabolism and PK (DMPK) scientists in drug discovery projects. This is typically performed by using in vitro-in vivo extrapolation (IVIVE) based on mechanistic PK models. In recent years, machine learning (ML), with its ability to harness patterns from previous outcomes to predict future events, has gained increased popularity in application to absorption, distribution, metabolism, and excretion (ADME) sciences.

Amount of Melanin Granules in Human Hair Defines the Absorption and Conversion to Heat of Light Energy in the Visible Spectrum.

One of the known important functions of hair is protection from extensive sunlight. This protection is accomplished in large part due to natural hair pigmentation which is known to reflect the number of melanin granules (melanosomes) in the hair shaft, and melanin variants. Melanin takes in excessive light energy and converts it to heat in a process called absorption; heat is then dissipated into the environment as infrared radiation, thereby protecting the underlying skin.

Electron microscopy study of the central retinal fovea in Pied flycatcher: evidence of a mechanism of light energy transmission through the retina.

We present unique ultrastructural data on avian retinal cells. Presently and earlier (Zueva et al., 2016) we explored distribution of intermediate filaments (IFs) in retinal cells of the Pied flycatcher (, Passeriformes, Aves) in the central foveolar zone.

Applying Two Orthogonal Methods to Assess Accuracy of Plasma Protein Binding Measurements for Highly Bound Compounds.

Significant advances have been made over the years to accurately measure plasma protein binding (PPB) of highly bound compounds. However, because of perceived uncertainty based on historical suboptimal methods and limitation of radiochemical purity of radiolabeled materials, current regulatory guidelines recommend using an arbitrary cutoff fraction unbound (f) of 0.01 as the lower limit for drug-drug interaction (DDI) prediction.

Accumulation of Amyloid Beta (Aβ) Peptide on Blood Vessel Walls in the Damaged Brain after Transient Middle Cerebral Artery Occlusion.

It is well known that amyloid beta (Aβ) peptides are generated in blood vessels, released into the brain during thrombosis, and temporarily accumulate in this organ after injury. Here we demonstrate that 24 h after transient middle cerebral artery occlusion (tMCAO), one of the standard models of focal ischemic stroke, Aβ peptide accumulates in the brain, concentrating on the blood vessel walls. Because Aβ oligomers are known to induce significant damage to brain cells, they act as an additional damaging factor during ischemic stroke.

Quantum mechanism of light energy propagation through an avian retina.

Taking into account the ultrastructure of the Pied Flycatcher foveal retina reported earlier and the earlier reported properties of Müller cell (MC) intermediate filaments (IFs) isolated from vertebrate retina, we proposed a quantum mechanism (QM) of light energy transfer from the inner limiting membrane level to visual pigments in the photoreceptor cells. This mechanism involves electronic excitation energy transfer in a donor-acceptor system, with the IFs excited by photons acting as energy donors, and visual pigments in the photoreceptor cells acting as energy acceptors. It was shown earlier that IFs with diameter 10 nm and length 117 μm isolated from vertebrate eye retina demonstrate properties of light energy guide, where exciton propagates along such IFs from MC endfeet area to photoreceptor cell area.

Tissue Transparency In Vivo.

In vivo tissue transparency in the visible light spectrum is beneficial for many research applications that use optical methods, whether it involves in vivo optical imaging of cells or their activity, or optical intervention to affect cells or their activity deep inside tissues, such as brain tissue. The classical view is that a tissue is transparent if it neither absorbs nor scatters light, and thus absorption and scattering are the key elements to be controlled to reach the necessary transparency. This review focuses on the latest genetic and chemical approaches for the decoloration of tissue pigments to reduce visible light absorption and the methods to reduce scattering in live tissues.

Localization of αA-Crystallin in Rat Retinal Müller Glial Cells and Photoreceptors.

Transparent cells in the vertebrate optical tract, such as lens fiber cells and corneal epithelium cells, have specialized proteins that somehow permit only a low level of light scattering in their cytoplasm. It has been shown that both cell types contain (1) beaded intermediate filaments as well as (2) α-crystallin globulins. It is known that genetic and chemical alterations to these specialized proteins induce cytoplasmic opaqueness and visual complications.

Comparison of sensory structures on the antenna of different species of Philopotamidae (Insecta: Trichoptera).

Structure and distribution of sensilla were studied in sixteen species of the caddisfly family Philopotamidae. Their antennae bear numerous curved trichoid and pseudoplacoid sensilla and fewer coronal, styloconic and chaetoid sensilla on the flagellar segments. The most numerous pseudoplacoid sensilla have non-specific localization.

Spectral selectivity model for light transmission by the intermediate filaments in Müller cells.

Presently we continue our studies of the quantum mechanism of light energy transmission in the form of excitons by axisymmetric nanostructures with electrically conductive walls. Using our theoretical model, we analyzed the light energy transmission by biopolymers forming optical channels within retinal Müller cells. There are specialized intermediate filaments (IF) 10-18nm in diameter, built of electrically conductive polypeptides.

Draft Genome Sequence of a Multidrug-Resistant Nosocomial Strain That Persisted in a Hospital in Kemerovo, Russian Federation.

is a frequent cause of health care-associated infections and has led to multiple outbreaks. Here, we report the draft genome of a multidrug-resistant strain 189 which was isolated in 2012 as a predominant clone in a neonatal hospital in Kemerovo.

Platelets are responsible for the accumulation of β-amyloid in blood clots inside and around blood vessels in mouse brain after thrombosis.

Introduction: Platelets contain beta-amyloid precursor protein (APP) as well as Aβ peptide (Aβ) that can be released upon activation. During thrombosis, platelets are concentrated in clots and activated.

Methods: We used in vivo fluorescent analysis and electron microscopy in mice to determine to what degree platelets are concentrated in clots.

Errata: Quantum mechanism of light transmission by the intermediate filaments in some specialized optically transparent cells.

[This corrects the article DOI: 10.1117/1.NPh.

Quantum mechanism of light transmission by the intermediate filaments in some specialized optically transparent cells.

Some very transparent cells in the optical tract of vertebrates, such as the lens fiber cells, possess certain types of specialized intermediate filaments (IFs) that have essential significance for their transparency. The exact mechanism describing why the IFs are so important for transparency is unknown. Recently, transparency was described also in the retinal Müller cells (MCs).

[MULTI-LEVEL EVALUATION OF BIOSOCIAL RISK FACTORS OF HIV-INFECTION AMONG MIGRANT WORKERS].

Aim: Multi-level evaluation by case-control method of social, sociocultural and behavioural risk factors of HIV-infection spread among male migrant workers arriving to Russia from near abroad countries.

Materials And Methods: Interviews of migrants, that had appealed for medical examination for work permit, were carried out for detection of risk factors. Results of interviewing of 191 migrants with HIV-infection (case group) and 190 migrants without HIV-infection (control group) were analyzed.

Foveolar Müller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency.

Specialized intermediate filaments (IFs) have critical importance for the clearness and uncommon transparency of vertebrate lens fiber cells, although the physical mechanisms involved are poorly understood. Recently, an unusual low-scattering light transport was also described in retinal Müller cells. Exploring the function of IFs in Müller cells, we have studied the morphology and distribution pattern of IFs and other cytoskeletal filaments inside the Müller cell main processes in the foveolar part of the avian (pied flycatcher) retina.

Draft Genome Sequence of Enterococcus faecium Strain 58m, Isolated from Intestinal Tract Content of a Woolly Mammoth, Mammuthus primigenius.

Enterococcus faecium 58m is a putative ancient nonpathogenic strain isolated from the intestinal content of an adult woolly mammoth (Mammuthus primigenius). Here, we report its draft genome sequence, consisting of 60 contigs. In silico genomic analysis was performed to determine the genetic features and pathogenic potential of this microorganism.

Prevalence and Antibiotic Resistance of Carbapenemase-Producing Gram-Negative Bacteria in Saint Petersburg and Some Other Regions of the Russian Federation.

Carbapenemase-producing gramnegative bacteria, which hydrolyze most offi-lactams, including carbapenems, is of global health care system threat. The number of the known carbapenemases is constantly increasing, however only four types are widely distributed: NDM-type, KPC-type, OXA-48-type and VIM-type. The frequency of carbapenemase-producing Klebsiellapneumoniae in hospitals of Saint Petersburg reached 9.

On the Role of the Blood Vessel Endothelial Microvilli in the Blood Flow in Small Capillaries.

Endothelial microvilli that protrude into the capillary lumen, although invisible in the optical microscopy, may play an important role in the blood flow control in the capillaries. Because of the plug effects, the width of the gap between the capillary wall and the blood cell is especially critical for the blood flow dynamics in capillaries, while microvilli located on the capillary wall can easily control the velocity of the blood flow. We report that microvilli in the capillaries of different vertebrate species have similar characteristics and density, suggesting similarities between the respective regulation mechanisms.

Model of Polarization Selectivity of the Intermediate Filament Optical Channels.

Recently we have analyzed light transmission and spectral selectivity by optical channels in Müller cells and other transparent cells, proposing a model of their structure, formed by specialized intermediate filaments [1,2]. Our model represents each optical channel by an axially symmetric tube with conductive walls. Presently, we analyze the planar polarization selectivity in long nanostructures, using the previously developed approach extended to structures of the elliptic cross-section.

Müller cell alignment in bird fovea: possible role in vision.

Birds which possess high visual acuity, such as eagles and falcons, are known to have retinas with a deep conically curved central foveal pit. There have been different attempts to explain the importance of this particular shape of the fovea in visual resolution. Recently, the function of Müller cells as "light fibers" was discovered, showing how the endfeet of Müller cells trap the light and then transfer it to a single cone photoreceptor.