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. We showcase controllable manipulation between these states using short current pulses and achieve a nondestructive readout by a nearby junction. Our observations pave the way toward ultrafast and energy-efficient digital Josephson electronics.

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.e. disappeared in a few minutes, whereas in RKM and RHM it was stable in this time scale. We attribute this difference to the increased activity of mitochondrial GST in liver. We report data on the detection of glutathione-fluazinam conjugates by mass-spectrometry, thin layer chromatography and capillary electrophoresis after incubation of fluazinam with RLM but not with RKM, which supports the assumption of the tissue specificity of the conjugation.

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. Compared to the UB-4 derivatives, UB-3 esters proved to be stronger uncouplers: the most effective of them caused a pronounced increase in the respiration rate of isolated rat heart mitochondria (RHM) at submicromolar concentrations. Both of these series of UB derivatives exhibited a striking difference between their uncoupling patterns in mitochondria isolated from liver and heart or kidney, namely: a pronounced but transient decrease in membrane potential, followed by its recovery, was observed after the addition of these compounds to isolated rat liver mitochondria (RLM), while the depolarization of RHM and rat kidney mitochondria (RKM) was rather stable under the same conditions. Interestingly, partial reversal of this depolarization in RHM and RKM was caused by carboxyatractyloside, an inhibitor of ATP/ADP translocase, thereby pointing to the involvement of this mitochondrial membrane protein in the uncoupling activity of both UB-3 and UB-4 esters. The fast membrane potential recovery in RLM uncoupled by the addition of the UB esters was apparently associated with hydrolysis of these compounds, catalyzed by mitochondrial aldehyde dehydrogenase (ALDH2), being in high abundance in liver compared to other tissues. Protonophoric properties of the UB derivatives in isolated mitochondria were confirmed by measurements of RHM swelling in the presence of potassium acetate. In model bilayer lipid membranes (liposomes), proton-carrying activity of UB-3 esters was demonstrated by measuring fluorescence response of the pH-dependent dye pyranine. Electrophysiological experiments on identified neurons from Lymnaea stagnalis demonstrated low neurotoxicity of UB-3 esters. Resazurin-based cell viability assay showed low toxicity of UB-3 esters to HEK293 cells and primary human fibroblasts. Thus, the present results enable us to consider UB-3 esters as effective tissue-specific protonophoric mitochondrial uncouplers.

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. The smallness of the vortex allows a broad-range tunability by nanoscale manipulation of vortices in a micron-size array of vortex traps. We show that a phase shift in a device containing just a few vortex traps can be reconfigured between a large number of quantized states in a broad [-3π, +3π] range.

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: 25.5 million) through the federal and departmental reporting system. We identified the regions with a favourable or unfavourable tuberculosis epidemiological profile and ranked them as low or high priority for specific interventions. FINDINGS: The median number of tuberculosis notifications in the regions was 123.3 per 100 000 population (range: 54.5-265.7) in 2003, decreasing to 82.3 per 100 000 (range: 52.9-178.3) in 2016. We found large variations in the tuberculosis epidemiological profile across different regions. The principal coordinate analysis revealed that three aggregated indicators accounted for 55% of the variation. The first coordinate corresponded to tuberculosis prevalence and case notifications in the regions; the second to the severity of the disease among patients; and the third to the percentage of multidrug-resistant tuberculosis among tuberculosis patients. The regions where intervention was most urgently needed were Chukotka Autonomous Okrug, Jewish Autonomous Oblast and Tyva Republic. CONCLUSION: The variability in tuberculosis epidemiology across regions was likely due to differences in the quality of antituberculosis services. Precision in defining necessary interventions, as determined through the principal coordinate analysis approach, can guide focused tuberculosis control efforts.

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. The cell represents a fluxonic quantum dot containing a small superconducting island, an asymmetric notch for the vortex entrance, a guiding track, and a vortex trap. We determine the optimal geometrical parameters for operation at zero magnetic field and the conditions for controllable vortex manipulation by short current pulses. We report ultrafast vortex motion with velocities more than an order of magnitude faster than those expected for macroscopic superconductors. This phenomenon is attributed to strong interactions with the edges of a mesoscopic island, combined with the nonlinear reduction of flux-flow viscosity due to the nonequilibrium effects in the track. Our results show that such cells can be scaled down to sizes comparable to the London penetration depth, ∼100 nm, and can enable ultrafast switching on the picosecond scale with ultralow energy per operation, ∼10-19 J.

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. Here, we report measurements of the CATR effect on the activity of a large number of conventional and novel uncouplers in isolated mammalian mitochondria. Despite the broad variety of chemical structures, CATR attenuated the uncoupling efficacy of all the anionic protonophores in rat heart mitochondria with high abundance of ANT, whereas the effect was much less pronounced or even absent, e.g. for SF6847, in rat liver mitochondria with low ANT content. The fact that the uncoupling action is tissue specific for a broad spectrum of anionic protonophores is highlighted here for the first time. Only with the cationic uncoupler ellipticine and the channel-forming peptide gramicidin A, no sensitivity to CATR was found even in rat heart mitochondria. By contrast, with the recently described ester-stabilized ylidic protonophores [Kirsanov et al. Bioelectrochemistry 2023], the stimulating effect of CATR was discovered both in liver and heart mitochondria.

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. The oscillating electric field is generated internally via the ac-Josephson effect. In this work, I present a distributed, active patch antenna model of a Josephson oscillator. It takes into account the internal Josephson electrodynamics and allows for the determination of the effective input resistance, which couples the Josephson current to cavity modes in the transmission line formed by the junction. The model provides full characterization of Josephson oscillators and explains the origin of the low radiative power efficiency. Finally, I discuss the design of an optimized Josephson patch oscillator capable of reaching high efficiency and radiation power for emission into free space.

Word and bit line operation of a 1 × 1 µm2 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. First, we test scalability and demonstrate that the cells can be straightforwardly miniaturized to submicron sizes. Second, we emphasize the importance of conscious geometrical engineering. In the studied devices we introduce an asymmetric easy track for vortex motion and show that it enables a controllable manipulation of vortex states. Finally, we perform a detailed analysis of word and bit line operation of a 1 × 1 µm2 cell. High-endurance, non-volatile operation at zero magnetic field is reported. Remarkably, we observe that the combined word and bit line threshold current is significantly reduced compared to the bare word-line operation. This could greatly improve the selectivity of individual cell addressing in a multi-cell RAM. The achieved one square micron area is an important milestone and a significant step forward towards creation of a dense cryogenic memory.

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. They are based on conventional niobium planar Josephson junctions, in which space/time symmetry is broken by a combination of self-field effect from nonuniform bias and stray fields from a trapped Abrikosov vortex. We demonstrate that nonreciprocity of critical current in such diodes can reach an order of magnitude and rectification efficiency can exceed 70%. Furthermore, we can easily change the diode polarity and switch nonreciprocity on/off by changing the bias configuration and by trapping/removing of a vortex. This facilitates a memory functionality. We argue that such a diode-with-memory can be used for a future generation of in-memory superconducting computers.

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 x Si1- x /Nb junctions. The arrays exhibit profound cavity mode resonances, corresponding to the formation of standing waves at the electrode/substrate interface. We observe that resonant steps in the current-voltage characteristics appear above some threshold number of junctions, N th ≈ 100, and then progressively enhance in amplitude with further increment of the number of junctions in the resistive oscillating state. We use an external detector to measure the emission of electromagnetic waves. The emission power correlates with the step amplitude. Our results indicate that the emission is facilitated by the cavity modes in the electrodes. The modes are collectively excited by active junctions. In turn, the standing wave imprints its order on the array, facilitating mutual phase-locking of junctions. This provides an indirect coupling mechanism, allowing for the synchronization of junctions, which do not directly interact with each other. Our results demonstrate that electrodes can effectively work as a common external resonator, facilitating long-range phase-locking of large junction arrays with sizes larger than the emitted wavelength.

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. The phenomenon is attributed to the phase locking of junctions in different arrays via a common electromagnetic field. Remarkably, the gain can exceed the factor of two expected for a simple constructive interference of two oscillators. The larger gain is explained by an additional consequence of mutual interaction between two large arrays. Mutual phase locking of large arrays does not only result in constructive interference outside the arrays, but also improved synchronization of junctions inside each array. Our conclusion is supported by numerical modelling.

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. According to TLC and HPLC data, incubation of RLM with UB-4 esters caused their hydrolysis, which led to disappearance of the uncoupling activity (recoupling). Both mitochondrial recoupling and hydrolysis of UB-4 esters were suppressed by inhibitors of mitochondrial aldehyde dehydrogenase (ALDH2), disulfiram and daidzin, thus pointing to the involvement of this enzyme in the recoupling of RLM incubated with UB-4 esters. The protonophoric mechanism of mitochondrial uncoupling by UB-4 esters was proved in experiments with artificial bilayer lipid membranes (BLM): these compounds induced proton-selective electrical current across planar BLM and caused dissipation of pH gradient on liposomes. UB-4 esters showed antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Mycobacterium smegmatis.

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. We derived analytical expressions and verified them experimentally on nano-scale Nb-PtNi-Nb and Nb-CuNi-Nb Josephson junctions.

Design aspects of Bi2Sr2CaCu2O8+δ 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 Bi2Sr2CaCu2O8+δ. Two types of devices are considered containing either a conventional large single crystal or a whisker. We perform numerical simulations for various geometrical configurations and parameters and make a comparison with experimental data for the two types of devices. It is demonstrated that the structure and the geometry of both the superconductor and the electrodes play important roles. In crystal-based devices an overlap between the crystal and the electrode leads to appearance of a large parasitic capacitance, which shunts terahertz emission and prevents impedance matching with open space. The overlap is avoided in whisker-based devices. Furthermore, the whisker and the electrodes form a turnstile (crossed-dipole) antenna facilitating good impedance matching. This leads to more than an order of magnitude enhancement of the radiation power efficiency in whisker-based, compared to crystal-based, devices. These results are in good agreement with presented experimental data.

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-2 s-1) 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. There was only a trace fluorescence kinetics at the low PPFD, but noticeable fluorescence kinetics under the red light was observed at the low and moderate PPFD. Particularly, the moderate red illumination of Chlorella cells excited a high chlorophyll fluorescence kinetics along with the absence of oxygen evolution that suggests anoxygenic photosynthesis. In contrast, the blue light induced a significant oxygen evolution as well as fluorescence kinetics already at low PPFD which were both further increased with the PPFD increasing. In addition, a high value of the chromatic divergence of quantum yield of photosystem II was revealed between the red and blue measuring light under high PPFD of the red actinic light.

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. We demonstrate how FORC can be used for detailed in situ characterization of magnetic states. It reveals that upon reduction of the external field, the magnetization in ferromagnetic layers first rotates in a coherent scissor-like manner, then switches abruptly into the antiparallel state and after that splits into the polydomain state, which gradually turns into the opposite parallel state. The polydomain state is manifested by a profound enhancement of resistance caused by a flux-flow phenomenon, triggered by domain stray fields. The scissor state represents the noncollinear magnetic state in which the unconventional odd-frequency spin-triplet order parameter should appear. The non-hysteretic nature of this state allows for reversible tuning of the magnetic orientation. Thus, we identify the range of parameters and the procedure for in situ control of devices based on S/F heterostructures.

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. The novel approaches of collapse therapy techniques and minimally invasive osteoplastic thoracoplasty increase the effectiveness of complex anti-TB therapy. Achieving the required selective collapse of lung tissue in destructive pulmonary TB, especially in cases of drug resistance and/or HIV coinfection, leads to bacteriologic conversion, cavity closure, and successful cure.

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. Based on this discovery, we demonstrate the possibility of the Josephson vortex generation and manipulation by the magnetic tip of a MFM, thus paving a way for the remote inspection and control of individual nano-components of superconducting quantum circuits.

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.