Spontaneous reversal of small molecule-induced mitochondrial uncoupling: the case of anilinothiophenes.

Tissue specificity can render mitochondrial uncouplers more promising as leading compounds for creating drugs against serious diseases. In search of tissue-specific uncouplers, we address anilinothiophenes as possible glutathione-S-transferase substrates (GST). Earlier, 'cyclic' uncoupling activity was reported for 5-bromo-N-(4-chlorophenyl)-3,4-dinitro-2-thiophenamine (BDCT) in isolated rat liver mitochondria (RLM).

Numerical Modeling of Vortex-Based Superconducting Memory Cells: Dynamics and Geometrical Optimization.

The lack of dense random-access memory is one of the main obstacles to the development of digital superconducting computers. It has been suggested that AVRAM cells, based on the storage of a single Abrikosov vortex-the smallest quantized object in superconductors-can enable drastic miniaturization to the nanometer scale. In this work, we present the numerical modeling of such cells using time-dependent Ginzburg-Landau equations.

Mitochondrial uncoupling caused by a wide variety of protonophores is differently sensitive to carboxyatractyloside in rat heart and liver mitochondria.

Mitochondrial uncoupling by small-molecule protonophores is generally accepted to proceed via transmembrane proton shuttling. The idea of facilitating this process by the adenine nucleotide translocase ANT originated primarily from the partial reversal of the DNP-induced mitochondrial uncoupling by the ANT inhibitor carboxyatractyloside (CATR). Recently, the sensitivity to CATR was also observed for the action of such potent OxPhos uncouplers as BAM15, SF6847, FCCP and niclosamide.

Controllable Manipulation of Semifluxon States in Phase-Shifted Josephson Junctions.

The utilization of Josephson vortices as information carriers in superconducting digital electronics is hindered by the lack of reliable displacement and localization mechanisms. In this Letter, we experimentally investigate planar Nb junctions with an intrinsic phase shift and nonreciprocity induced by trapped Abrikosov vortices. We demonstrate that the entrance of a single Josephson vortex into such junctions triggers the switching between metastable ±π semifluxon states.

The transient character of mitochondrial uncoupling by the popular fungicide fluazinam is specific for liver.

The popular fungicide fluazinam is known to exhibit an unusual cyclic pattern of the protonophoric uncoupling activity in isolated rat liver mitochondria (RLM), with membrane deenergization followed by spontaneous recoupling in the minute scale, which is associated with glutathione conjugation of fluazinam catalyzed by glutathione-S-transferase (GST). Here, we compare the fluazinam effect on RLM with that on rat kidney (RKM) and heart (RHM) mitochondria by monitoring three bioenergetic parameters: oxygen consumption rate, mitochondrial membrane potential and reduction of nucleotides. Only in RLM, the uncoupling activity of fluazinam was transient, i.

Word and bit line operation of a 1 × 1 μm superconducting vortex-based memory.

The lack of dense random access memory is one of the main bottlenecks for the creation of a digital superconducting computer. In this work we study experimentally vortex-based superconducting memory cells. Three main results are obtained.

A distributed active patch antenna model of a Josephson oscillator.

Optimization of Josephson oscillators requires a quantitative understanding of their microwave properties. A Josephson junction has a geometry similar to a microstrip patch antenna. However, it is biased by a dc current distributed over the whole area of the junction.

Observation of collective excitation of surface plasmon resonances in large Josephson junction arrays.

Josephson junctions can be used as sources of microwave radiation. However, synchronization of many junctions is required for achieving a coherent amplification of the emitted power. In this work we present an experimental study of large arrays containing up to one thousand Nb/Nb Si /Nb junctions.

Coherent amplification of radiation from two phase-locked Josephson junction arrays.

We analyze experimentally and theoretically mutual phase locking and electromagnetic interaction between two linear arrays with a large number of Josephson junctions. Arrays with different separation, either on the same chip or on two separate substrates are studied. We observe a large coherent gain, up to a factor of three, of emitted power from two simultaneously biased arrays, compared to the sum of powers from two individually biased arrays.

Alkyl esters of 7-hydroxycoumarin-3-carboxylic acid as potent tissue-specific uncouplers of oxidative phosphorylation: Involvement of ATP/ADP translocase in mitochondrial uncoupling.

An impressive body of evidence has been accumulated now on sound beneficial effects of mitochondrial uncouplers in struggling with the most dangerous pathologies such as cancer, infective diseases, neurodegeneration and obesity. To increase their efficacy while gaining further insight in the mechanism of the uncoupling action has been remaining a challenge. Encouraged by our previous promising results on lipophilic derivatives of 7-hydroxycoumarin-4-acetic acid (UB-4 esters), here, we use a 7-hydroxycoumarin-3-carboxylic acid scaffold to synthesize a new series of 7-hydroxycoumarin (umbelliferone, UB)-derived uncouplers of oxidative phosphorylation - alkyl esters of umbelliferone-3-carboxylic acid (UB-3 esters) with varying carbon chain length.

Demonstration of a superconducting diode-with-memory, operational at zero magnetic field with switchable nonreciprocity.

Diode is one of the basic electronic components. It has a nonreciprocal current response, associated with a broken space/time reversal symmetry. Here we demonstrate prototypes of superconducting diodes operational at zero magnetic field.

Alkyl esters of umbelliferone-4-acetic acid as protonophores in bilayer lipid membranes and ALDH2-dependent soft uncouplers in rat liver mitochondria.

A great variety of coumarin-related compounds, both natural and synthetic, being often brightly fluorescent, have shown themselves beneficial in medicine for both therapeutic and imaging purposes. Here, in search for effective uncouplers of oxidative phosphorylation, we synthesized a series of 7-hydroxycoumarin (umbelliferone, UB) derivatives combining rather high membrane affinity with the presence of a hydroxyl group deprotonable at physiological pH - alkyl esters of umbelliferone-4-acetic acid (UB-4 esters) differing in alkyl chain length. Addition of UB-4 esters to isolated rat liver mitochondria (RLM) resulted in their rapid depolarization, unexpectedly followed by membrane potential recovery on a minute time scale.

Design aspects of BiSrCaCuO THz sources: optimization of thermal and radiative properties.

Impedance matching and heat management are important factors influencing the performance of terahertz sources. In this work we analyze thermal and radiative properties of such devices based on mesa structures of a layered high-temperature superconductor BiSrCaCuO. Two types of devices are considered containing either a conventional large single crystal or a whisker.

In situ transport characterization of magnetic states in Nb/Co superconductor/ferromagnet heterostructures.

Employment of the non-trivial proximity effect in superconductor/ferromagnet (S/F) heterostructures for the creation of novel superconducting devices requires accurate control of magnetic states in complex thin-film multilayers. In this work, we study experimentally in-plane transport properties of microstructured Nb/Co multilayers. We apply various transport characterization techniques, including magnetoresistance, Hall effect, and the first-order-reversal-curves (FORC) analysis.

Accurate Determination of the Josephson Critical Current by Lock-In Measurements.

Operation of Josephson electronics usually requires determination of the Josephson critical current Ic, which is affected both by fluctuations and measurement noise. Lock-in measurements allow obviation of 1/f noise, and therefore, provide a major advantage in terms of noise and accuracy with respect to conventional dc measurements. In this work we show both theoretically and experimentally that the Ic can be accurately extracted using first and third harmonic lock-in measurements of junction resistance.

Reconfigurable Josephson Phase Shifter.

Phase shifter is one of the key elements of quantum electronics. In order to facilitate operation and avoid decoherence, it has to be reconfigurable, persistent, and nondissipative. In this work, we demonstrate prototypes of such devices in which a Josephson phase shift is generated by coreless superconducting vortices.

Chlorophyll fluorescence kinetics and oxygen evolution in Chlorella vulgaris cells: Blue vs. red light.

Oxygen evolution and chlorophyll fluorescence kinetics in cells of the Chlorella vulgaris strain (Europolytest, Russia) were studied under low, moderate and high photosynthetic photon flux densities (PPFD 40, 130 and 350 μmol photons m s) of the red and blue actinic light. A novel method of a pulse amplitude modulated (PAM) Fourier chlorophyll fluorometry was applied to obtain photoinduction curves simultaneously for the red and blue measuring light for one sample. It was found that the red light did not induce oxygen evolution at low and moderate PPFD, whereas at high PPFD it caused a declining oxygen release.

Variations in tuberculosis prevalence, Russian Federation: a multivariate approach.

Objective: To analyse the epidemiological trends of tuberculosis in the Siberian and Far Eastern federal districts, the areas with the highest disease burden in the Russian Federation.

Methods: We applied principal coordinate analysis to study a total of 68 relevant variables on tuberculosis epidemiology, prevention and control. Data on these variables were collected over 2003-2016 in all 21 regions of the Siberian federal district and Far Eastern federal district (total population: 25.

Author Correction: Local Josephson vortex generation and manipulation with a Magnetic Force Microscope.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Local Josephson vortex generation and manipulation with a Magnetic Force Microscope.

Josephson vortices play an essential role in superconducting quantum electronics devices. Often seen as purely conceptual topological objects, 2π-phase singularities, their observation and manipulation are challenging. Here we show that in Superconductor-Normal metal-Superconductor lateral junctions Josephson vortices have a peculiar magnetic fingerprint that we reveal in Magnetic Force Microscopy (MFM) experiments.

Modern Collapse Therapy for Pulmonary Tuberculosis.

Multidrug-resistant tuberculosis (TB), extensively drug-resistant TB, and TB-human immunodeficiency virus (HIV) coinfection require a special approach in anti-TB treatment. Most patients cannot be successfully cured by conventional chemotherapy alone. They need a modern approach using minimally invasive therapeutic and surgical techniques.

Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis.

Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. 54 patients with MS were included in the study.

Thoracoplasty for Tuberculosis in the Twenty-first Century.

A new modification of osteoplastic collapse thoracoplasty performed with a minimally invasive approach has been proposed. This operation is a variant of extrapleural thoracoplasty used in the treatment of destructive tuberculosis. The benefits of the proposed method, the surgical techniques, and the results of the authors' research are described.

BCG infection in mice is promoted by naïve mesenchymal stromal cells (MSC) and suppressed by poly(A:U)-conditioned MSC.

Mesenchymal stromal cells (MSC) transplantation is an actively studied therapeutic approach used in regenerative medicine and in the field of control of immunoinflammatory response. Conditioning of MSC in culture can form their predominantly pro- or anti-inflammatory phenotypes. We demonstrated that poly(A:U)-conditioning of bone marrow-derived mouse MSC induced predominantly pro-inflammatory phenotype.