Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins.

A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.

Dependence of Guaiacol Peroxidase Activity and Lipid Peroxidation Rate in Drooping Birch (Betula pendula Roth) and Tillet (Tilia cordata Mill) Leaf on Motor Traffic Pollution Intensity.

Hormesis and paradoxical effects are frequently found for different plant parameters. These phenomena were also observed for lipid peroxidation (LP) rate at environmental pollution. However, the role of antioxidant enzymes, particularly guaiacol peroxidases (GPX), in a nonmonotonic variation in the LP rate remains insufficiently explored.

Hormesis and Paradoxical Effects of Drooping Birch (Betula pendula Roth) Parameters Under Motor Traffic Pollution.

Various plant indexes are used or recommended for bioindication. However, the nonmonotonic dose-response dependences (hormesis and paradoxical effects) of these indexes are insufficiently explored upon exposure to pollution. We studied the dependences of these Betula pendula indexes on the intensity of motor traffic pollution.

Sierolomorpha sogdiana spec. nov. from Central Asia, and a World catalogue of Sierolomorphidae (Hymenoptera).

Sierolomorpha sogdiana Lelej & Mokrousov, spec. nov. is described and illustrated from Central Asia (Uzbekistan).

Structure and Thermal Expansion of Calcium-Thorium Apatite, [Ca4]F[Ca2Th4]T[(SiO4)6]O2.

Thorium silicate apatite with the formula [Ca3.84Th0.16]F[Ca2.

Perspectives in Intraoperative Diagnostics of Human Gliomas.

Amongst large a variety of oncological diseases, malignant gliomas represent one of the most severe types of tumors. They are also the most common type of the brain tumors and account for over half of the astrocytic tumors. According to different sources, the average life expectancy of patients with various glioblastomas varies between 10 and 12 months and that of patients with anaplastic astrocytic tumors between 20 and 24 months.

A Spiking Neural Network in sEMG Feature Extraction.

We have developed a novel algorithm for sEMG feature extraction and classification. It is based on a hybrid network composed of spiking and artificial neurons. The spiking neuron layer with mutual inhibition was assigned as feature extractor.

Thermodynamic Properties of Carbosilane Dendrimers of the Sixth Generation with Ethylene Oxide Terminal Groups.

The temperature dependences of heat capacities of carbosilane dendrimers of the sixth generation with ethyleneoxide terminal groups, denoted as G6[(OCH2CH2)1OCH3]256 and G6[(OCH2CH2)3OCH3]256, were measured in the temperature range from T = (6 to 520) K by precision adiabatic calorimetry and differential scanning calorimetry (DSC). In the above temperature range the physical transformations, such as glass transition and high-temperature relaxation transition, were detected. The standard thermodynamic characteristics of the revealed transformations were determined and analyzed.

Dissipative dynamics in a quantum bistable system: crossover from weak to strong damping.

The dissipative dynamics of a quantum bistable system coupled to a Ohmic heat bath is investigated beyond the spin-boson approximation. Within the path-integral approach to quantum dissipation, we propose an approximation scheme which exploits the separation of time scales between intra- and interwell (tunneling) dynamics. The resulting generalized master equation for the populations in a space localized basis enables us to investigate a wide range of temperatures and system-environment coupling strengths.

Nitroxide malonate methanofullerene as biomimetic model of interaction of nitroxide species with antioxidants.

Bis-nitroxide malonate methanofullerene (NO)2-MF was studied as a biomimetic model of reduction-oxidation activity with natural compounds-cytochrome c (cyt c), dihydroquercetin (DHQ), ascorbic acid (AA) and synthetic drug-1-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine (xymedon(®)). (NO)2-MF may be used as the component of Langmuir monolayers on an aqueous subphase and as the adsorbate on silica gel. The activity of (NO)2-MF in the reaction with cyt c was compared with the effect of nitroxide species such as gaseous nitric oxide, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) by using UV-vis and EPR-spectra.

Extended particle-in-cell schemes for physics in ultrastrong laser fields: Review and developments.

We review common extensions of particle-in-cell (PIC) schemes which account for strong field phenomena in laser-plasma interactions. After describing the physical processes of interest and their numerical implementation, we provide solutions for several associated methodological and algorithmic problems. We propose a modified event generator that precisely models the entire spectrum of incoherent particle emission without any low-energy cutoff, and which imposes close to the weakest possible demands on the numerical time step.

Variation potential in higher plants: Mechanisms of generation and propagation.

Long-distance intercellular electrical signals, including variation potential (VP) in higher plants, are a potential mechanism of coordinate functional responses in different plant cells under action of stressors. VP, which is caused by damaging factors (e.g.

Control of Mycobacterial Infections in Mice Expressing Human Tumor Necrosis Factor (TNF) but Not Mouse TNF.

Tumor necrosis factor (TNF) is an important cytokine for host defense against pathogens but is also associated with the development of human immunopathologies. TNF blockade effectively ameliorates many chronic inflammatory conditions but compromises host immunity to tuberculosis. The search for novel, more specific human TNF blockers requires the development of a reliable animal model.

Passive estimation of internal temperatures making use of broadband ultrasound radiated by the body.

The internal temperatures of plasticine models and the human forearm in vivo were determined, based on remote measurements of their intrinsic ultrasonic radiation. For passive detection of the thermal ultrasonic radiation an acoustic radiometer was developed, based on a broadband 0.8-3.

Hydrogen-bond-assisted organocatalytic acetalization of secondary alcohols: experimental and theoretical studies.

An efficient method was developed for the acetalization of secondary alcohols in the presence of simple protic pyridinium salts. Direct correlations between the structure and activity of the synthesized catalysts were described. Stabilization via hydrogen bonding of the hemiacetal intermediate by the pyridine derivatives, along with an appropriate increase in the reaction rate, was revealed.

Evaluation of the open time of calcium channels at variation potential generation in wheat leaf cells.

The role of ions in the generation and mechanism of propagation of variation potential (VP) has been widely investigated. It is likely that Ca(2+) influx via calcium channels is an initial stage of VP; however, development of long-term membrane depolarization requires prolonged open times of calcium channels. We investigated depolarization time in the present study.

Modern anti-cytokine therapy of autoimmune diseases.

The emergence of genetically engineered biological agents opened new prospects in the treatment of autoimmune and inflammatory diseases. Cytokines responsible for regulation of a wide range of processes during development of the normal immune response are among the most successful therapeutic targets. Studies carried out in recent decades and accompanied by rapid development of biotechnology have promoted establishing in detail the role and place of cytokines in autoimmune and inflammatory pathologies.

Electrogenic properties of the Na⁺/K⁺ ATPase control transitions between normal and pathological brain states.

Ionic concentrations fluctuate significantly during epileptic seizures. In this study, using a combination of in vitro electrophysiology, computer modeling, and dynamical systems analysis, we demonstrate that changes in the potassium and sodium intra- and extracellular ion concentrations ([K(+)] and [Na(+)], respectively) during seizure affect the neuron dynamics by modulating the outward Na(+)/K(+) pump current. First, we show that an increase of the outward Na(+)/K(+) pump current mediates termination of seizures when there is a progressive increase in the intracellular [Na(+)].

Dependence of Dandelion (Taraxacum officinale Wigg.) Seed Reproduction Indices on Intensity of Motor Traffic Pollution.

Dandelion (Taraxacum officinale Wigg.) seed reproduction indices such as the total number of seeds, the number of normally developed seeds and underdeveloped seeds per anthodium, and seed weight are suggested to assess the level of environmental pollution (bioindication). However, the non-monotonic dose-response dependences (hormesis and paradoxical effects) of these indices are insufficiently explored upon exposure to pollution.

Field-reversed bubble in deep plasma channels for high-quality electron acceleration.

We study hollow plasma channels with smooth boundaries for laser-driven electron acceleration in the bubble regime. Contrary to the uniform plasma case, the laser forms no optical shock and no etching at the front. This increases the effective bubble phase velocity and energy gain.

Nonlinear decay of random waves described by an integrodifferential equation.

The evolution of random nonlinear waves (high-intensity noise) in a dissipative and dispersive media is studied. To describe wave processes, the mathematical model in the form of a nonlinear integrodifferential equation is used. The concrete integrand kernels are determined by both frequency-dependent absorption and velocity of the wave.

Robust design of polyrhythmic neural circuits.

Neural circuit motifs producing coexistent rhythmic patterns are treated as building blocks of multifunctional neuronal networks. We study the robustness of such a motif of inhibitory model neurons to reliably sustain bursting polyrhythms under random perturbations. Without noise, the exponential stability of each of the coexisting rhythms increases with strengthened synaptic coupling, thus indicating an increased robustness.

Ionic nature of burn-induced variation potential in wheat leaves.

Variation potential (VP) in higher plants cells is a transitory depolarization of the plasma membrane occurring in response to external damage. The effects of VP on different physiological processes are actively studied, but little is known about their ionic nature, which limits the interpretation of VP-induced functional changes. It is thought that VP generation is based on transient inactivation of plasma membrane proton pumps and is not connected to passive ionic fluxes.

Standard Thermodynamic Functions of Tripeptides -Formyl-l-methionyl-l-leucyl-l-phenylalaninol and -Formyl-l-methionyl-l-leucyl-l-phenylalanine Methyl Ester.

The heat capacities of tripeptides -formyl-l-methionyl-l-leucyl-l-phenylalaninol (-f-MLF-OH) and -formyl-l-methionyl-l-leucyl-l-phenylalanine methyl ester (-f-MLF-OMe) were measured by precision adiabatic vacuum calorimetry over the temperature range from = (6 to 350) K. The tripeptides were stable over this temperature range, and no phase change, transformation, association, or thermal decomposition was observed. The standard thermodynamic functions: molar heat capacity , enthalpy () - (0), entropy (), and Gibbs energy () - (0) of peptides were calculated over the range from = (0 to 350) K.

Radiation-reaction trapping of electrons in extreme laser fields.

A radiation-reaction trapping (RRT) of electrons is revealed in the near-QED regime of laser-plasma interaction. Electrons quivering in laser pulse experience radiation reaction (RR) recoil force by radiating photons. When the laser field reaches the threshold, the RR force becomes significant enough to compensate for the expelling laser ponderomotive force.