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Human voltage-gated sodium (hNaV) channels are responsible for initiating and propagating action potentials in excitable cells, and mutations have been associated with numerous cardiac and neurological disorders. hNaV1.7 channels are expressed in peripheral neurons and are promising targets for pain therapy. The tarantula venom peptide protoxin-II (PTx2) has high selectivity for hNaV1.7 and is a valuable scaffold for designing novel therapeutics to treat pain. Here, we used computational modeling to study the molecular mechanisms of the state-dependent binding of PTx2 to hNaV1.7 voltage-sensing domains (VSDs). Using Rosetta structural modeling methods, we constructed atomistic models of the hNaV1.7 VSD II and IV in the activated and deactivated states with docked PTx2. We then performed microsecond-long all-atom molecular dynamics (MD) simulations of the systems in hydrated lipid bilayers. Our simulations revealed that PTx2 binds most favorably to the deactivated VSD II and activated VSD IV. These state-specific interactions are mediated primarily by PTx2's residues R22, K26, K27, K28, and W30 with VSD and the surrounding membrane lipids. Our work revealed important protein-protein and protein-lipid contacts that contribute to high-affinity state-dependent toxin interaction with the channel. The workflow presented will prove useful for designing novel peptides with improved selectivity and potency for more effective and safe treatment of pain.

Ion channels are integral membrane proteins facilitating permeation of ions through aqueous pores across cell membranes. They are essential to numerous physiological processes such as nerve impulses and heartbeats and are key therapeutic targets due to their involvement in various diseases. This dissertation employs advanced computational techniques to investigate the structure and function of ion channels, specifically focusing on the human (denoted by the prefix “h”) voltage-gated sodium channel hNaV1.7, voltage-gated potassium channel hERG, and small-conductance calcium-activated potassium channel hSK2, which are critical therapeutic targets for pain management and the treatment of cardiac arrhythmias. A brief overview of ion channels and lipid membranes as well as their experimental and computational studies is provided in Chapters 1 and 2, followed by three specific ion channel related stories in Chapters 3 through 5 and finishing with closing remarks and future outlook in Chapter 6.The first story focuses on the human voltage-gated sodium channel hNaV1.7, a prime target for pain therapy due to its predominant expression in peripheral nociceptive neurons. We explored the interaction between the hNaV1.7 channel’s voltage sensing domains (VSDs) II and IV in different conformational states and the tarantula venom peptide protoxin-II, a potent and selective inhibitor of the channel. Our computational models revealed that protoxin-II exhibits state-specific binding modes to different states of the channel’s VSDs, illuminating the molecular basis of its inhibitory effects through enhanced hNaV1.7 channel deactivation and inactivation. Additionally, we identified key channel’s residues involved in the toxin binding and their energetic contributions. These findings are crucial for the rational design of novel pain therapeutics with improved selectivity and potency. The second story shifts focus to the human voltage-gated potassium channel hKV11.1, also known as hERG (h

Nuclear spins with hyperfine coupling to single electron spins are highly valuable quantum bits. Here we probe and characterize the particularly rich nuclear-spin environment around single silicon vacancy color centers (V2) in 4H-SiC. By using the electron spin-3/2 qudit as a four level sensor, we identify several sets of Si29 and C13 nuclear spins through their hyperfine interaction. We extract the major components of their hyperfine coupling via optical detected nuclear magnetic resonance, and assign them to shells in the crystal via the density function theory simulations. We utilize the ground-state level anticrossing of the electron spin for dynamic nuclear polarization and achieve a nuclear-spin polarization of up to 98±6%. We show that this scheme can be used to detect the nuclear magnetic resonance signal of individual spins and demonstrate their coherent control. Our work provides a detailed set of parameters and first steps for future use of SiC as a multiqubit memory and quantum computing platform.

In the context of planet formation, growth from micron-sized grains to kilometer-sized planetesimals is a crucial question. Since the dust growth rate depends on the amount of dust, realizing planet formation scenarios based on dust growth is challenging in environments with low metallicity, i.e. less dust. We investigate dust growth during disk evolution, particularly focusing on the relationship with metallicity. We perform two-dimensional thin-disk hydrodynamic simulations to track the disk evolution over 300 kyr from its formation. The dust motion is solved separately from the gas motion, with its distribution changing due to drag forces from the gas. Dust size growth is also accounted for, with the magnitude of the drag force varying according to the dust size. We employ three models with metallicities of 1.0, 0.1, and 0.01 ${\rm Z}_{\odot}$, i.e. dust-to-gas mass ratios of 10$^{-2}$, 10$^{-3}$, and 10$^{-4}$, respectively. In the disks with the metallicities $\ge0.1$ ${\rm Z}_{\odot}$, the dust radii reach cm sizes, consistent with estimations from the dust growth timescale. Conversely, for the metallicity of 0.01 ${\rm Z}_{\odot}$, the maximum dust size is only 10$^{-2}$ cm, with almost no growth observed across the entire disk scale ($\sim$100 au). At the metallicities $\ge0.1$ ${\rm Z}_{\odot}$, the decoupling between grown dust and gas leads to non-uniform dust-to-gas mass ratios. However, deviations from the canonical value of this ratio have no impact on the gravitational instability of the disk. The formation of dust rings is confirmed in the innermost part of the disk ($\sim$10--30 au). The dust rings where the dust-to-gas mass ratio is enhanced, and the Stokes number reaches $\sim$0.1, are suitable environments for the streaming instability. We conjecture that planetesimal formation occurs through the streaming instability in these dust rings., Comment: 13 pages, 12 figures, submitted to A&A

The formation of solid macroscopic grains (pebbles) in protoplanetary discs is the first step toward planet formation. We aim to study the distribution of pebbles and the chemical composition of their ice mantles in a young protoplanetary disc. We use the two-dimensional hydrodynamical code FEOSAD in the thin-disc approximation, which is designed to model the global evolution of a self-gravitating viscous protoplanetary disc taking into account dust coagulation and fragmentation, thermal balance, and phase transitions and transport of the main volatiles (H$_2$O, CO$_{2}$, CH$_{4}$ and CO), which can reside in the gas, on small dust ($<1$ $\mu$m), on grown dust ($>1$ $\mu$m) and on pebbles. We model the dynamics of the protoplanetary disc from the cloud collapse to the 500 kyr moment. We determine the spatial distribution of pebbles and composition of their ice mantles and estimate the mass of volatiles on pebbles, grown dust and small dust. We show that pebbles form as early as 50 kyr after the disc formation and exist until the end of simulation (500 kyr), providing prerequisites for planet formation. All pebbles formed in the model are covered by icy mantles. Using a model considering accretion and desorption of volatiles onto dust/pebbles, we find that the ice mantles on pebbles consist mainly of H$_2$O and CO$_{2}$, and are carbon-depleted compared to gas and ices on small and grown dust, which contain more CO and CH$_4$. This suggests a possible dominance of oxygen in the composition of planets formed from pebbles under these conditions., Comment: 18 pages, 9 figures, 1 table, accepted to MNRAS

FU Orionis type objects (fuors) are characterized by rapid (tens to hundreds years) episodic outbursts, during which the luminosity increases by orders of magnitude. One of the possible causes of such events is a close encounter between stars and protoplanetary disks. Numerical simulations show that the fuor-like outburst ignition requires a very close encounter ranging from a few to a few tens of au. In contrast, the observed stellar objects in fuor binaries are usually hundreds of au apart. Simple mathematical estimates show that if such a close approach took place, the binary stellar components would have an unrealistic relative velocity, at least an order of magnitude greater than the observed velocity dispersion in young stellar clusters. Thus, the bursts are either triggered with a certain delay after passage of the periastron or their ignition does not necessary require a close encounter and hence the outburst is not caused by the primordial gravitational perturbation of the protoplanetary disk. In this work, an encounter of a star surrounded by a protoplanetary disk with a diskless external stellar object was modeled using numerical hydrodynamics simulations. We showed that even fly-bys with a relatively large periastron (at least 500 au) can result in fuor-like outbursts. Moreover, the delay between the periastron passage and the burst ignition can reach several kyr. It was shown for the first time by means of numerical modeling that the perturbation of the disk caused by the external object can trigger a cascade process, which includes the development of the thermal instability in the innermost disk followed by the magneto-rotational instability ignition. Because of the sequential development of these instabilities, the rapid increase in the accretion rate occurs, resulting in the luminosity increase by more than two orders of magnitude., Comment: Accepted for publication by Astronomy Reports

Aims. The initial stages of planet formation may start concurrently with the formation of a gas-dust protoplanetary disk. This makes the study of the earliest stages of protoplanetary disk formation crucially important. Here we focus on dust growth and pebble formation in a protoplanetary disk that is still accreting from a parental cloud core. Methods. We have developed an original three-dimensional numerical hydrodynamics code, which computes the collapse of rotating clouds and disk formation on nested meshes using a novel hybrid Coarray Fortran-OpenMP approach for distributed and shared memory parallelization. Dust dynamics and growth are also included in the simulations. Results. We found that the dust growth from $\sim 1~\mu$m to 1-10~mm already occurs in the initial few thousand years of disk evolution but the Stokes number hardly exceeds 0.1 because of higher disk densities and temperatures compared to the minimum mass Solar nebular. The ratio of the dust-to-gas vertical scale heights remains rather modest, 0.2--0.5, which may be explained by the perturbing action of spiral arms that develop in the disk soon after its formation. The dust-to-gas mass ratio in the disk midplane is highly nonhomogeneous throughout the disk extent and is in general enhanced by a factor of several compared to the fiducial 1:100 value. Low St hinders strong dust accumulation in the spiral arms compared to the rest of the disk and the nonsteady nature of the spirals is also an obstacle. The spatial distribution of pebbles in the disk midplane exhibits a highly nonhomogeneous and patchy character. The total mass of pebbles in the disk increases with time and reaches a few tens of Earth masses after a few tens of thousand years of disk evolution. Abridged., Comment: Accepted for publication by Astronomy & Astrophysics

The Spin Physics Detector collaboration proposes to install a universal detector in the second interaction point of the NICA collider under construction (JINR, Dubna) to study the spin structure of the proton and deuteron and other spin-related phenomena using a unique possibility to operate with polarized proton and deuteron beams at a collision energy up to 27 GeV and a luminosity up to $10^{32}$ cm$^{-2}$ s$^{-1}$. As the main goal, the experiment aims to provide access to the gluon TMD PDFs in the proton and deuteron, as well as the gluon transversity distribution and tensor PDFs in the deuteron, via the measurement of specific single and double spin asymmetries using different complementary probes such as charmonia, open charm, and prompt photon production processes. Other polarized and unpolarized physics is possible, especially at the first stage of NICA operation with reduced luminosity and collision energy of the proton and ion beams. This document is dedicated exclusively to technical issues of the SPD setup construction.

The use of one-bit analog-to-digital converter (ADC) has been considered as a viable alternative to high resolution counterparts in realizing and commercializing massive multiple-input multiple-output (MIMO) systems. However, the issue of discarding the amplitude information by one-bit quantizers has to be compensated. Thus, carefully tailored methods need to be developed for one-bit channel estimation and data detection as the conventional ones cannot be used. To address these issues, the problems of one-bit channel estimation and data detection for MIMO orthogonal frequency division multiplexing (OFDM) system that operates over uncorrelated frequency selective channels are investigated here. We first develop channel estimators that exploit Gaussian discriminant analysis (GDA) classifier and approximated versions of it as the so-called weak classifiers in an adaptive boosting (AdaBoost) approach. Particularly, the combination of the approximated GDA classifiers with AdaBoost offers the benefit of scalability with the linear order of computations, which is critical in massive MIMO-OFDM systems. We then take advantage of the same idea for proposing the data detectors. Numerical results validate the efficiency of the proposed channel estimators and data detectors compared to other methods. They show comparable/better performance to that of the state-of-the-art methods, but require dramatically lower computational complexities and run times.

In the framework of the IAEA Coordinated Research Project on In-Vessel Melt Retention, a benchmark of CFD simulations, devoted to thermal-hydraulic behavior of the light metal layer involves several research organizations: KTH of Sweden, SSTC NRS of Ukraine, ÚJV Řež of Czech Republic and CEA of France. This work aims at better simulating the focusing effect phenomenon leading to a heat flux peak along the height of the light metal layer, which is formed above the oxide layer in a stratified corium pool configuration during a PWR severe accident. This is a known safety issue compromising the reactor vessel integrity. The first benchmark step provides a solid foundation to the CFD schemes (physical models, meshes) by comparing the results of CFD simulations with thermal-hydraulic experimental data obtained using water as simulating fluid in a representative and quite laminar configuration. Then a similar but highly turbulent case, of higher height, is considered for more complex validation of the numerical simulation approach. Results with different turbulent models are compared against experimental data. On the strength of this encouraging work, a simulation of the same height configuration but considering steel fluid under severe accident conditions is foreseen at the final stage of this benchmark., Part of ISBN 9784888982566QC 20231214

Simple Summary In the bodies of animals, including birds, gene expression leads to the synthesis of many proteins. To provide optimal cellular and organismal properties and functions, many genes should work in concert, reaching certain balanced relationships (or networks) between them and the intensities of their expression. Here, we studied the expression of several genes responsible for muscle formation and growth in chick embryos of diverse breeds belonging to various utility types. Using two mathematical (fractal) models and the respective indices, we showed that there are specific coordinated patterns of gene expression in the embryonic breast and thigh muscles. These patterns correlated with growth rate of chicks after hatching and depended on a utility type of the breeds studied. Overall, the proposed models contributed to an expanded understanding of the coordinated gene expression in early development and growth, providing additional characteristics of genetic diversity in chickens. Abstract Elements of fractal analysis are widely used in scientific research, including several biological disciplines. In this study, we hypothesized that chicken breed biodiversity manifests not only at the phenotypic level, but also at the genetic-system level in terms of different profiles of fractal conformity and bioconsolidation in the early myogenesis gene expression. To demonstrate this effect, we developed two mathematical models that describe the fractal nature of the expression of seven key genes in the embryonic breast and thigh muscles in eight breeds of meat, dual purpose, egg and game types. In the first model, we produced breed-specific coefficients of gene expression conformity in each muscle type using the slopes of regression dependencies, as well as an integral myogenesis gene expression index (MGEI). Additionally, breed fractal dimensions and integral myogenesis gene expression fractal dimension index (MGEFDI) were determined. The second gene expression mod

Due to long-term domestication, breeding and divergent selection, a vast genetic diversity in poultry currently exists, with various breeds being characterized by unique phenotypic and genetic features. Assuming that differences between chicken breeds divergently selected for economically and culturally important traits manifest as early as possible in development and growth stages, we aimed to explore breed-specific patterns and interrelations of embryo myogenesis, nitric oxide (NO) metabolism and post-hatch growth rate (GR). These characteristics were explored in eight breeds of different utility types (meat-type, dual purpose, egg-type, game, and fancy) by incubating 70 fertile eggs per breed. To screen the differential expression of seven key myogenesis associated genes (MSTN, GHR, MEF2C, MYOD1, MYOG, MYH1, and MYF5), quantitative real-time PCR was used. We found that myogenesis associated genes expressed in the breast and thigh muscles in a coordinated manner showing breed specificity as a genetic diversity signature among the breeds studied. Notably, coordinated (“accord”) expression patterns of MSTN, GHR, and MEFC2 were observed both in the breast and thigh muscles. Also, associated expression vectors were identified for MYOG and MYOD1 in the breast muscles and for MYOG and MYF5 genes in the thigh muscles. Indices of NO oxidation and post-hatch growth were generally concordant with utility types of breeds, with meat-types breeds demonstrating higher NO oxidation levels and greater GR values as compared to egg-type, dual purpose, game and fancy breeds. The results of this study suggest that differences in early myogenesis, NO metabolism and post-hatch growth are breed-specific; they appropriately reflect genetic diversity and accurately capture the evolutionary history of divergently selected chicken breeds.

Due to long-term domestication, breeding and divergent selection, a vast genetic diversity in poultry currently exists, with various breeds being characterized by unique phenotypic and genetic features. Assuming that differences between chicken breeds divergently selected for economically and culturally important traits manifest as early as possible in development and growth stages, we aimed to explore breed-specific patterns and interrelations of embryo myogenesis, nitric oxide (NO) metabolism and post-hatch growth rate (GR). These characteristics were explored in eight breeds of different utility types (meat-type, dual purpose, egg-type, game, and fancy) by incubating 70 fertile eggs per breed. To screen the differential expression of seven key myogenesis associated genes (MSTN, GHR, MEF2C, MYOD1, MYOG, MYH1, and MYF5), quantitative real-time PCR was used. We found that myogenesis associated genes expressed in the breast and thigh muscles in a coordinated manner showing breed specificity as a genetic diversity signature among the breeds studied. Notably, coordinated (“accord”) expression patterns of MSTN, GHR, and MEFC2 were observed both in the breast and thigh muscles. Also, associated expression vectors were identified for MYOG and MYOD1 in the breast muscles and for MYOG and MYF5 genes in the thigh muscles. Indices of NO oxidation and post-hatch growth were generally concordant with utility types of breeds, with meat-types breeds demonstrating higher NO oxidation levels and greater GR values as compared to egg-type, dual purpose, game and fancy breeds. The results of this study suggest that differences in early myogenesis, NO metabolism and post-hatch growth are breed-specific; they appropriately reflect genetic diversity and accurately capture the evolutionary history of divergently selected chicken breeds.

Due to long-term domestication, breeding and divergent selection, a vast genetic diversity in poultry currently exists, with various breeds being characterized by unique phenotypic and genetic features. Assuming that differences between chicken breeds divergently selected for economically and culturally important traits manifest as early as possible in development and growth stages, we aimed to explore breed-specific patterns and interrelations of embryo myogenesis, nitric oxide (NO) metabolism and post-hatch growth rate (GR). These characteristics were explored in eight breeds of different utility types (meat-type, dual purpose, egg-type, game, and fancy) by incubating 70 fertile eggs per breed. To screen the differential expression of seven key myogenesis associated genes (MSTN, GHR, MEF2C, MYOD1, MYOG, MYH1, and MYF5), quantitative real-time PCR was used. We found that myogenesis associated genes expressed in the breast and thigh muscles in a coordinated manner showing breed specificity as a genetic diversity signature among the breeds studied. Notably, coordinated (“accord”) expression patterns of MSTN, GHR, and MEFC2 were observed both in the breast and thigh muscles. Also, associated expression vectors were identified for MYOG and MYOD1 in the breast muscles and for MYOG and MYF5 genes in the thigh muscles. Indices of NO oxidation and post-hatch growth were generally concordant with utility types of breeds, with meat-types breeds demonstrating higher NO oxidation levels and greater GR values as compared to egg-type, dual purpose, game and fancy breeds. The results of this study suggest that differences in early myogenesis, NO metabolism and post-hatch growth are breed-specific; they appropriately reflect genetic diversity and accurately capture the evolutionary history of divergently selected chicken breeds.

The thermal instability of accretion disks is widely used to explain the activity of cataclysmic variables, but its development in protoplanetary disks has been studied in less detail. We present a semi-analytical stationary model for calculating the midplane temperature of a gas and dust disk around a young star. The model takes into account gas and dust opacities, as well as the evaporation of dust at temperatures above 1000 K. Using this model, we calculate the midplane temperature distributions of the disk under various assumptions about the source of opacity and the presence of dust. We show that when all considered processes are taken into account, the heat balance equation in the region r<1 au has multiple temperature solutions. Thus, the conditions for thermal instability are met in this region. To illustrate the possible influence of instability on the accretion state in a protoplanetary disk, we consider a viscous disk model with alpha parameterization of turbulent viscosity. We show that in such a model the disk evolution is non-stationary, with alternating phases of accumulation of matter in the inner disk and its rapid accretion onto the star, leading to an episodic accretion pattern. These results indicate that this instability needs to be taken into account in evolutionary models of protoplanetary disks., Comment: Published in Astronomy Reports Vol. 67, No. 5, pp. 470-482 (2023)

Direct imaging observations of planets revealed that wide-orbit ($>10$ au) giant planets exist even around subsolar-metallicity host stars and do not require metal-rich environments for their formation. A possible formation mechanism of wide-orbit giant planets in subsolar-metallicity environments is the gravitational fragmentation of massive protoplanetary discs. Here, we follow the long-term evolution of the disc for 1 Myr after its formation, which is comparable to disc lifetime, by way of a two-dimensional thin-disc hydrodynamic simulation with the metallicity of 0.1 ${\rm Z}_{\odot}$. We find a giant protoplanet that survives until the end of the simulation. The protoplanet is formed by the merger of two gaseous clumps at $\sim$0.5 Myr after disc formation, and then it orbits $\sim$200 au from the host star for $\sim$0.5 Myr. The protoplanet's mass is $\sim$10 ${\rm M}_{\rm J}$ at birth and gradually decreases to 1 ${\rm M}_{\rm J}$ due to the tidal effect from the host star. The result provides the minimum mass of 1 ${\rm M}_{\rm J}$ for protoplanets formed by gravitational instability in a subsolar-metallicity disc. We anticipate that the mass of a protoplanet experiencing reduced mass loss thanks to the protoplanetary contraction in higher resolution simulations can increase to $\sim$10 ${\rm M}_{\rm J}$. We argue that the disc gravitational fragmentation would be a promising pathway to form wide-orbit giant planets with masses of $\ge1$ ${\rm M}_{\rm J}$ in subsolar-metallicity environments., Comment: 11 pages, 8 figures, submitted to MNRAS

We compute the evolution and rotational periods of young stars, using the MESA code, starting from a stellar seed, and take protostellar accretion, stellar winds, and the magnetic star-disk interaction into account. Furthermore, we add a certain fraction of the energy of accreted material into the stellar interior as additional heat and combine the resulting effects on stellar evolution with the stellar spin model. For different combinations of parameters, stellar periods at an age of 1~Myr range between 0.6~days and 12.9~days. Thus, during the relatively short time period of 1~Myr, a significant amount of stellar angular momentum can already be removed by the interaction between the star and its accretion disk. The amount of additional heat added into the stellar interior, the accretion history, and the presence of disk and stellar winds have the strongest impact on the stellar spin evolution during the first million years. The slowest stellar rotations result from a combination of strong magnetic fields, a large amount of additional heat, and effective winds. The fastest rotators combine weak magnetic fields and ineffective winds or result from a small amount of additional heat added to the star. Scenarios that could lead to such configurations are discussed. Different initial rotation periods of the stellar seed, on the other hand, quickly converges and do not affect the stellar period at all. Our model matches up to 90\% of the observed rotation periods in six young ($\lesssim 3$~Myr) clusters. Based on these intriguing results, we motivate to combine our model with a hydrodynamic disk evolution code to self-consistently include several important aspects such as episodic accretion events, magnetic disk winds, internal, and external photo-evaporation. (Shortened), Comment: 17 pages, 15 figures, accepted for publication in A&A

Modeling the dynamics of the formation and evolution of protostellar disks as well as the history of stellar mass accretion typically involve the numerical solution of complex systems of coupled differential equations. The resulting mass accretion history of protostars is known to be highly episodic due to recurrent instabilities and also exhibits short timescale flickering. By leveraging the strong predictive abilities of neural networks, we extract some of the critical temporal dynamics experienced during the mass accretion including periods of instability. Particularly, we utilize a novel form of the Echo-State Neural Network (ESN), which has been shown to efficiently deal with data having inherent nonlinearity. We introduce the use of Optimized-ESN (Opt-ESN) to make model-independent time series forecasting of mass accretion rate in the evolution of protostellar disks. We apply the network to multiple hydrodynamic simulations with different initial conditions and exhibiting a variety of temporal dynamics to demonstrate the predictability of the Opt-ESN model. The model is trained on simulation data of $\sim 1-2$ Myr, and achieves predictions with a low normalized mean square error ($\sim 10^{-5}$ to $10^{-3}$) for forecasts ranging between 100 and 3800 yr. This result shows the promise of the application of machine learning based models to time-domain astronomy., Comment: 16 pages, 13 figures

Most existing convolutional dictionary learning (CDL) algorithms are based on batch learning, where the dictionary filters and the convolutional sparse representations are optimized in an alternating manner using a training dataset. When large training datasets are used, batch CDL algorithms become prohibitively memory-intensive. An online-learning technique is used to reduce the memory requirements of CDL by optimizing the dictionary incrementally after finding the sparse representations of each training sample. Nevertheless, learning large dictionaries using the existing online CDL (OCDL) algorithms remains highly computationally expensive. In this paper, we present a novel approximate OCDL method that incorporates sparse decomposition of the training samples. The resulting optimization problems are addressed using the alternating direction method of multipliers. Extensive experimental evaluations using several image datasets show that the proposed method substantially reduces computational costs while preserving the effectiveness of the state-of-the-art OCDL algorithms.

Simple Summary In the bodies of animals, including birds, gene expression leads to the synthesis of many proteins. To provide optimal cellular and organismal properties and functions, many genes should work in concert, reaching certain balanced relationships (or networks) between them and the intensities of their expression. Here, we studied the expression of several genes responsible for muscle formation and growth in chick embryos of diverse breeds belonging to various utility types. Using two mathematical (fractal) models and the respective indices, we showed that there are specific coordinated patterns of gene expression in the embryonic breast and thigh muscles. These patterns correlated with growth rate of chicks after hatching and depended on a utility type of the breeds studied. Overall, the proposed models contributed to an expanded understanding of the coordinated gene expression in early development and growth, providing additional characteristics of genetic diversity in chickens. Abstract Elements of fractal analysis are widely used in scientific research, including several biological disciplines. In this study, we hypothesized that chicken breed biodiversity manifests not only at the phenotypic level, but also at the genetic-system level in terms of different profiles of fractal conformity and bioconsolidation in the early myogenesis gene expression. To demonstrate this effect, we developed two mathematical models that describe the fractal nature of the expression of seven key genes in the embryonic breast and thigh muscles in eight breeds of meat, dual purpose, egg and game types. In the first model, we produced breed-specific coefficients of gene expression conformity in each muscle type using the slopes of regression dependencies, as well as an integral myogenesis gene expression index (MGEI). Additionally, breed fractal dimensions and integral myogenesis gene expression fractal dimension index (MGEFDI) were determined. The second gene expression mod

Due to long-term domestication, breeding and divergent selection, a vast genetic diversity in poultry currently exists, with various breeds being characterized by unique phenotypic and genetic features. Assuming that differences between chicken breeds divergently selected for economically and culturally important traits manifest as early as possible in development and growth stages, we aimed to explore breed-specific patterns and interrelations of embryo myogenesis, nitric oxide (NO) metabolism and post-hatch growth rate (GR). These characteristics were explored in eight breeds of different utility types (meat-type, dual purpose, egg-type, game, and fancy) by incubating 70 fertile eggs per breed. To screen the differential expression of seven key myogenesis associated genes (MSTN, GHR, MEF2C, MYOD1, MYOG, MYH1, and MYF5), quantitative real-time PCR was used. We found that myogenesis associated genes expressed in the breast and thigh muscles in a coordinated manner showing breed specificity as a genetic diversity signature among the breeds studied. Notably, coordinated (“accord”) expression patterns of MSTN, GHR, and MEFC2 were observed both in the breast and thigh muscles. Also, associated expression vectors were identified for MYOG and MYOD1 in the breast muscles and for MYOG and MYF5 genes in the thigh muscles. Indices of NO oxidation and post-hatch growth were generally concordant with utility types of breeds, with meat-types breeds demonstrating higher NO oxidation levels and greater GR values as compared to egg-type, dual purpose, game and fancy breeds. The results of this study suggest that differences in early myogenesis, NO metabolism and post-hatch growth are breed-specific; they appropriately reflect genetic diversity and accurately capture the evolutionary history of divergently selected chicken breeds.

Aims. Our aim is to derive a fast and accurate method for computing the gravitational potential of astrophysical objects with high contrasts in density, for which nested or adaptive meshes are required. Methods. We present an extension of the convolution method for computing the gravitational potential to the nested Cartesian grids. The method makes use of the convolution theorem to compute the gravitational potential using its integral form. Results. A comparison of our method with the iterative outside-in conjugate gradient and generalized minimal residual methods for solving the Poisson equation using nonspherically symmetric density configurations has shown a comparable performance in terms of the errors relative to the analytic solutions. However, the convolution method is characterized by several advantages and outperforms the considered iterative methods by factors 10--200 in terms of the runtime, especially when graphics processor units are utilized. The convolution method also shows an overall second-order convergence, except for the errors at the grid interfaces where the convergence is linear. Conclusions. High computational speed and ease in implementation can make the convolution method a preferred choice when using a large number of nested grids. The convolution method, however, becomes more computationally costly if the dipole moments of tightly spaced gravitating objects are to be considered at coarser grids., Comment: Accepted for publication in Astronomy & Astrophysics

The effect of accretion bursts on massive young stellar objects (MYSOs) represents a new research field in the study of young stars and their environment. We aim to investigate the impact of an accretion burst on massive disks with different types of envelopes and to study the effects of an accretion burst on the temperature structure and the chemistry of the disk. We focus on water and methanol as chemical species for this paper. The thermochemical code of PRODIMO (PROtoplanetary DIsk MOdel) is used to perform simulation of high mass protoplanetary disk models with different types of envelopes under the presence of an accretion burst. The models in question represent different evolutionary stages of protostellar objects. We calculate and show the chemical abundances in three phases of the simulation (pre-burst, burst, and post-burst). More heavily embedded disks show higher temperatures. The impact of the accretion burst is mainly characterized by the desorption of chemical species present in the disk and envelope from the dust grains to the gas phase. When the post-burst phase starts, the sublimated species freeze out again. The degree of sublimation depends strongly on the type of envelope the disk is embedded in. An accretion burst in more massive envelopes produces stronger desorption of the chemical species. However, our models show that the timescale for the chemistry to reach the pre-burst state is independent of the type of envelope. The study shows that the disk's temperature increases with a more massive envelope enclosing it. Thus, the chemistry of MYSOs in earlier stages of their evolution reacts stronger to an accretion burst than at later stages where the envelope has lost most of its mass or has been dissipated. The study of the impact of accretion bursts could also provide helpful theoretical context to the observation of methanol masers in massive disks., Comment: 16 pages, 14 figures

Object-centric architectures usually apply a differentiable module to the entire feature map to decompose it into sets of entity representations called slots. Some of these methods structurally resemble clustering algorithms, where the cluster's center in latent space serves as a slot representation. Slot Attention is an example of such a method, acting as a learnable analog of the soft k-means algorithm. Our work employs a learnable clustering method based on the Gaussian Mixture Model. Unlike other approaches, we represent slots not only as centers of clusters but also incorporate information about the distance between clusters and assigned vectors, leading to more expressive slot representations. Our experiments demonstrate that using this approach instead of Slot Attention improves performance in object-centric scenarios, achieving state-of-the-art results in the set property prediction task., Comment: 17 pages, 6 figures

Close encounters between young stellar objects in star forming clusters are expected to dramatically perturb circumstellar disks. Such events are witnessed in numerical simulations of star formation, but few direct observations of ongoing encounters have been made. Here we report sub-0".1 resolution Atacama Large Millimeter Array (ALMA) and Jansky Very Large Array (JVLA) observations towards the million year old binary protostar Z CMa in dust continuum and molecular line emission. A point source ~4700 au from the binary has been discovered at both millimeter and centimeter wavelengths. It is located along the extension of a ~2000 au streamer structure previously found in scattered light imaging, whose counterpart in dust and gas emission is also newly identified. Comparison with simulations shows signposts of a rare flyby event in action. Z CMa is a "double burster", as both binary components undergo accretion outbursts, which may be facilitated by perturbations to the host disk by flybys., Comment: Published in Nature Astronomy. Here is the authors' version with the Supplementary Information integrated into the Methods section

We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 Å from other K+ channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K+ channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state.

The voltage-gated potassium channel, KV11.1, encoded by the human Ether-à-go-go-Related Gene (hERG), is expressed in cardiac myocytes, where it is crucial for the membrane repolarization of the action potential. Gating of the hERG channel is characterized by rapid, voltage-dependent, C-type inactivation, which blocks ion conduction and is suggested to involve constriction of the selectivity filter. Mutations S620T and S641A/T within the selectivity filter region of hERG have been shown to alter the voltage dependence of channel inactivation. Because hERG channel blockade is implicated in drug-induced arrhythmias associated with both the open and inactivated states, we used Rosetta to simulate the effects of hERG S620T and S641A/T mutations to elucidate conformational changes associated with hERG channel inactivation and differences in drug binding between the two states. Rosetta modeling of the S641A fast-inactivating mutation revealed a lateral shift of the F627 side chain in the selectivity filter into the central channel axis along the ion conduction pathway and the formation of four lateral fenestrations in the pore. Rosetta modeling of the non-inactivating mutations S620T and S641T suggested a potential molecular mechanism preventing F627 side chain from shifting into the ion conduction pathway during the proposed inactivation process. Furthermore, we used Rosetta docking to explore the binding mechanism of highly selective and potent hERG blockers - dofetilide, terfenadine, and E4031. Our structural modeling correlates well with much, but not all, existing experimental evidence involving interactions of hERG blockers with key residues in hERG pore and reveals potential molecular mechanisms of ligand interactions with hERG in an inactivated state.

Optically addressable spin defects in silicon carbide (SiC) are an emerging platform for quantum information processing. Lending themselves to modern semiconductor nanofabrication, they promise scalable high-efficiency spin-photon interfaces. We demonstrate here nanoscale fabrication of silicon vacancy centres (VSi) in 4H-SiC without deterioration of their intrinsic spin-optical properties. In particular, we show nearly transform limited photon emission and record spin coherence times for single defects generated via ion implantation and in triangular cross section waveguides. For the latter, we show further controlled operations on nearby nuclear spin qubits, which is crucial for fault-tolerant quantum information distribution based on cavity quantum electrodynamics.

Beamforming is a signal processing technique to steer, shape, and focus an electromagnetic wave using an array of sensors toward a desired direction. It has been used in several engineering applications such as radar, sonar, acoustics, astronomy, seismology, medical imaging, and communications. With the advances in multi-antenna technologies largely for radar and communications, there has been a great interest on beamformer design mostly relying on convex/nonconvex optimization. Recently, machine learning is being leveraged for obtaining attractive solutions to more complex beamforming problems. This article captures the evolution of beamforming in the last twenty-five years from convex-to-nonconvex optimization and optimization-to-learning approaches. It provides a glimpse of this important signal processing technique into a variety of transmit-receive architectures, propagation zones, paths, and conventional/emerging applications., Comment: Accepted Paper in IEEE Signal Processing Magazine Special Issue on the 75th Anniversary of IEEE Signal Processing Society

Simultaneous sparse approximation (SSA) seeks to represent a set of dependent signals using sparse vectors with identical supports. The SSA model has been used in various signal and image processing applications involving multiple correlated input signals. In this paper, we propose algorithms for convolutional SSA (CSSA) based on the alternating direction method of multipliers. Specifically, we address the CSSA problem with different sparsity structures and the convolutional feature learning problem in multimodal data/signals based on the SSA model. We evaluate the proposed algorithms by applying them to multimodal and multifocus image fusion problems.

Graph Neural Networks (GNNs), particularly Graph Convolutional Neural Networks (GCNNs), have emerged as pivotal instruments in machine learning and signal processing for processing graph-structured data. This paper proposes an analysis framework to investigate the sensitivity of GCNNs to probabilistic graph perturbations, directly impacting the graph shift operator (GSO). Our study establishes tight expected GSO error bounds, which are explicitly linked to the error model parameters, and reveals a linear relationship between GSO perturbations and the resulting output differences at each layer of GCNNs. This linearity demonstrates that a single-layer GCNN maintains stability under graph edge perturbations, provided that the GSO errors remain bounded, regardless of the perturbation scale. For multilayer GCNNs, the dependency of system's output difference on GSO perturbations is shown to be a recursion of linearity. Finally, we exemplify the framework with the Graph Isomorphism Network (GIN) and Simple Graph Convolution Network (SGCN). Experiments validate our theoretical derivations and the effectiveness of our approach.

Aims. Dust plays a crucial role in the evolution of protoplanetary disks. We study the dynamics and growth of initially sub-$\mu m$ dust particles in self-gravitating young protoplanetary disks with various strengths of turbulent viscosity. We aim to understand the physical conditions that determine the formation and spatial distribution of pebbles when both disk self-gravity and turbulent viscosity can be concurrently at work. Methods. We perform the thin-disk hydrodynamics simulations of self-gravitating protoplanetary disks over an initial time period of 0.5 Myr using the FEOSAD code. Turbulent viscosity is parameterized in terms of the spatially and temporally constant $\alpha$-parameter, while the effects of gravitational instability on dust growth is accounted for by calculating the effective parameter $\alpha_{\rm GI}$. We consider the evolution of dust component including momentum exchange with gas, dust self-gravity, and also a simplified model of dust growth. Results. We find that the level of turbulent viscosity strongly affects the spatial distribution and total mass of pebbles in the disk. The $\alpha=10^{-2}$ model is viscosity-dominated, pebbles are completely absent, and dust-to-gas mass ratio deviates from the reference 1:100 value no more than by 30\% throughout the disk extent. On the contrary, the $\alpha=10^{-3}$ model and, especially, the $\alpha=10^{-4}$ model are dominated by gravitational instability. The effective parameter $\alpha+\alpha_{\rm GI}$ is now a strongly varying function of radial distance. As a consequence, a bottle neck effect develops in the innermost disk regions, which makes gas and dust accumulate in a ring-like structure. Abridged., Comment: Accepted for publication in Astronomy and Astrophysics

The effects of an accretion disk are crucial to understanding the evolution of young stars. During the combined evolution, stellar and disk parameters influence each other, motivating a combined stellar and disk model. This makes a combined numerical model, evolving the disk alongside the star, the next logical step in the progress of studying early stellar evolution. We aim to understand the effects of metallicity on the accretion disk and the stellar spin evolution during the T~Tauri phase. We combine the numerical treatment of a hydrodynamic disk with stellar evolution, including a stellar spin model, allowing a self-consistent calculation of the back-reactions between the individual components. We present the self-consistent theoretical evolution of T-Tauri stars coupled to a stellar disk. We find that disks in low metallicity environments are heated differently and have shorter lifetimes, compared to their solar metallicity counterparts. Differences in stellar radii, the contraction rate of the stellar radius, and the shorter disk lifetimes result in faster rotation of low metallicity stars. We present an additional explanation for the observed short disk lifetimes in low metallicity clusters. A combination of our model with previous studies (e.g., a metallicity-based photo-evaporation) could help to understand disk evolution and dispersal at different metallicities. Furthermore, the stellar spin evolution model includes several important effects, previously ignored (e.g., the stellar magnetic field strength and a realistic calculation of the disk lifetime) and we motivate to include our results as initial or input parameters for further spin evolution models, covering the stellar evolution towards and during the main sequence., Comment: accepted for publication in A&A

The burst mode of accretion in massive star formation is a scenario linking the initial gravitational collapse of parent pre-stellar cores to the properties of their gravitationally unstable discs and of their accretion-driven bursts. In this study, we present a series of high-resolution 3D radiation-hydrodynamics numerical simulations for young massive stars formed out of collapsing 100 Mo molecular cores spinning with several values of the ratio of rotational-to-gravitational energies beta=5%-9%. The models include the indirect gravitational potential caused by disc asymmetries. We find that this modifies the barycenter of the disc, causing significant excursions of the central star position, which we term stellar wobbling. The stellar wobbling slows down and protracts the development of gravitational instability in the disc, reducing the number and magnitude of the accretion-driven bursts undergone by the young massive stars, whose properties are in good agreement with that of the burst monitored from the massive protostar M17 MIR. Including stellar wobbling is therefore important for accurate modeling disc structures. Synthetic ALMA interferometric images in the millimeter waveband show that the outcomes of efficient gravitational instability such as spiral arms and gaseous clumps can be detected for as long as the disc is old enough and has already entered the burst mode of accretion., Comment: Accepted to MNRAS, see https://academic.oup.com/mnras/advance-article-abstract/doi/10.1093/mnras/stac2956/6761717?utm_source=advanceaccess&utm_campaign=mnras&utm_medium=email

3D simulations of high mass young stellar object (HMYSO) growth show that their circumstellar discs fragment onto multiple self-gravitating objects. Accretion of these by HMYSO may explain episodic accretion bursts discovered recently. We post-process results of a previous 3D simulation of a HMYSO disc with a 1D code that resolves the disc and object dynamics down to the stellar surface. We find that burst-like deposition of material into the inner disc seen in 3D simulations by itself does not always signify powerful accretion bursts. Only high density post-collapse clumps crossing the inner computational boundary may result in observable bursts. The rich physics of the inner disc has a significant impact on the expected accretion bursts: (1) In the standard turbulent viscosity discs, migrating objects can stall at a migration trap at the distance of a few au from the star. However, in discs powered by magnetised winds, the objects are able to cross the trap and produce bursts akin to those observed so far. (2) Migrating objects may interact with and modify the thermal (hydrogen ionisation) instability of the inner disc, which can be responsible for longer duration and lower luminosity bursts in HMYSOs. (3) If the central star is bloated to a fraction of an au by a previous episode of high accretion rate, or if the migrating object is particularly dense, a merger rather than a disc-mediated accretion burst results; (4) Object disruption bursts may be super-Eddington, leading to episodic feedback on HMYSO surroundings via powerful outflows., Comment: 19 pages, 16 figures, accepted to MNRAS

In the earliest phases of their evolution, stars gain mass through the acquisition of matter from their birth clouds. The widely accepted classical concept of early stellar evolution neglects the details of this accretion phase and assumes the formation of stars with large initial radii that contract gravitationally. In this picture, the common idea is that once the stars begin their fusion processes, they have forgotten their past. By analysing stellar oscillations in recently born stars, we show that the accretion history leaves a potentially detectable imprint on the stars' interior structures. Currently available data from space would allow discriminating between these more realistic accretion scenarios and the classical early stellar evolution models. This opens a window to investigate the interior structures of young pulsating stars that will also be of relevance for related fields, such as stellar oscillations in general and exoplanet studies., Comment: Open Access published in Nature Communications Supplementary Material is available at https://www.nature.com/articles/s41467-022-32882-0

We investigate the formation and evolution of "primordial" dusty rings occurring in the inner regions of protoplanetary discs, with the help of long-term, coupled dust-gas, magnetohydrodynamic simulations. The simulations are global and start from the collapse phase of the parent cloud core, while the dead zone is calculated via an adaptive $\alpha$ formulation by taking into account the local ionization balance. The evolution of the dusty component includes its growth and back reaction on to the gas. Previously, using simulations with only a gas component, we showed that dynamical rings form at the inner edge of the dead zone. We find that when dust evolution as well as magnetic field evolution in the flux-freezing limit are included, the dusty rings formed are more numerous and span a larger radial extent in the inner disc, while the dead zone is more robust and persists for a much longer time. We show that these dynamical rings concentrate enough dust mass to become streaming unstable, which should result in rapid planetesimal formation even in the embedded phases of the system. The episodic outbursts caused by the magnetorotational instability have significant impact on the evolution of the rings. The outbursts drain the inner disc of grown dust, however, the period between bursts is sufficiently long for the planetesimal growth via streaming instability.The dust mass contained within the rings is large enough to ultimately produce planetary systems with the core accretion scenario. The low mass systems rarely undergo outbursts and thus, the conditions around such stars can be especially conducive for planet formation., Comment: 21 pages, 14 figures

The spin evolution of young protostars, surrounded by an accretion disk, still poses problems for observations and theoretical models. In recent studies, the importance of the magnetic star-disk interaction for stellar spin evolution has been elaborated. The accretion disk in these studies, however, is only represented by a simplified model and important features are not considered. We combined the implicit hydrodynamic TAPIR disk code with a stellar spin evolution model. The influence of stellar magnetic fields on the disk dynamics, the radial position of the inner disk radius, as well as the influence of stellar rotation on the disk were calculated self-consistently. Within a defined parameter space, we can reproduce the majority of fast and slow rotating stars observed in young stellar clusters. Additionally, the back reaction of different stellar spin evolutionary tracks on the disk can be analyzed. Disks around fast rotating stars are located closer to the star. Consequently, the disk midplane temperature in the innermost disk region increases significantly compared to slow rotating stars. We can show the effects of stellar rotation on episodic accretion outbursts. The higher temperatures of disks around fast rotating stars result in more outbursts and a longer outbursting period over the disk lifetime. The combination of a long-term hydrodynamic disk and a stellar spin evolution model allows the inclusion of previously unconsidered effects such as the back-reaction of stellar rotation on the long-term disk evolution and the occurrence of accretion outbursts. However, a wider parameter range has to be studied to further investigate these effects. Additionally, a possible interaction between our model and a more realistic stellar evolution code (e.g., the MESA code) can improve our understanding of the stellar spin evolution and its effects on the pre-main sequence star., Comment: 12 pages, 7 figures, accepted by Astronomy & Astrophysics

We study the influence of different metallicities on the physical, thermal, and chemical properties of protoplanetary disks, and in particular on the formation and destruction of carbon-based molecules. With the thermo-chemical code ProoDIMO we investigate the impact of lower metallicities on the radiation field, disk temperature, and the abundance of different molecules (H$_2$O, CH$_4$, CO, CO$_2$, HCN, CN, HCO$^+$ and N$_2$H$^+$). We use a fiducial disk model as a reference model and produce two models with lower metallicity. The resulting influence on different chemical species is studied by analyzing their abundance distribution throughout the disk and their vertical column density. Furthermore, the formation and destruction reactions of the chemical species are studied. The results show a relation between the metallicity of the disk and the strength of the stellar radiation field inside the disk. As the metallicity decreases the radiation field is able to penetrate deeper regions of the disk. As a result, there is a stronger radiation field overall in the disk with lower metallicity which also heats up the disk. This triggers a series of changes in the chemical formation and destruction efficiencies for different chemical species. In most cases, the available species abundances change and have greater values compared to scaled-down abundances by constant factors. Metallicity has a clear impact on the snowline of the molecules studied here as well. As metallicity decreases the snowlines are pushed further out and existing snow rings shrink in size., Comment: 19 pages, 18 figures

Cosmic metallicity evolution possibly creates the diversity of star formation modes at different epochs. Gravitational fragmentation of circumstellar discs provides an important formation channel of multiple star systems, including close binaries. We here study the nature of disc fragmentation, systematically performing a suite of two-dimensional radiation-hydrodynamic simulations, in a broad range of metallicities, from the primordial to the solar values. In particular, we follow relatively long-term disc evolution over 15 kyr after the disc formation, incorporating the effect of heating by the protostellar irradiation. Our results show that the disc fragmentation occurs at all metallicities $1$--$0$ $Z_{\odot}$, yielding self-gravitating clumps. Physical properties of the clumps, such as their number and mass distributions, change with the metallicity due to different gas thermal evolution. For instance, the number of clumps is the largest for the intermediate metallicity range of $10^{-2}$--$10^{-5}$ $Z_{\odot}$, where the dust cooling is effective exclusively in a dense part of the disc and causes the fragmentation of spiral arms. The disc fragmentation is more modest for $1$--$0.1$ $Z_{\odot}$ thanks to the disc stabilization by the stellar irradiation. Such metallicity dependence agrees with the observed trend that the close binary fraction increases with decreasing metallicity in the range of $1$--$10^{-3}$ $Z_{\odot}$., Comment: 17 pages, 16 figures, submitted to MNRAS

Close encounters between young stellar objects in star forming clusters are expected to dramatically perturb circumstellar disks. Such events are witnessed in numerical simulations of star formation, but few direct observations of ongoing encounters have been made. Here we report sub-0".1 resolution Atacama Large Millimeter Array (ALMA) and Jansky Very Large Array (JVLA) observations towards the million year old binary protostar Z CMa in dust continuum and molecular line emission. A point source ~4700 au from the binary has been discovered at both millimeter and centimeter wavelengths. It is located along the extension of a ~2000 au streamer structure previously found in scattered light imaging, whose counterpart in dust and gas emission is also newly identified. Comparison with simulations shows signposts of a rare flyby event in action. Z CMa is a "double burster", as both binary components undergo accretion outbursts, which may be facilitated by perturbations to the host disk by flybys., Comment: Published in Nature Astronomy. Here is the authors' version with the Supplementary Information integrated into the Methods section

Colour centres are a promising quantum information platform, but coherence degradation after integration in nanostructures has hindered scalability. Here, the authors show that waveguide-integrated V-Si centres in SiC maintain spin-optical coherences, enabling nuclear high-fidelity spin qubit operations. Optically addressable spin defects in silicon carbide (SiC) are an emerging platform for quantum information processing compatible with nanofabrication processes and device control used by the semiconductor industry. System scalability towards large-scale quantum networks demands integration into nanophotonic structures with efficient spin-photon interfaces. However, degradation of the spin-optical coherence after integration in nanophotonic structures has hindered the potential of most colour centre platforms. Here, we demonstrate the implantation of silicon vacancy centres (V-Si) in SiC without deterioration of their intrinsic spin-optical properties. In particular, we show nearly lifetime-limited photon emission and high spin-coherence times for single defects implanted in bulk as well as in nanophotonic waveguides created by reactive ion etching. Furthermore, we take advantage of the high spin-optical coherences of V-Si centres in waveguides to demonstrate controlled operations on nearby nuclear spin qubits, which is a crucial step towards fault-tolerant quantum information distribution based on cavity quantum electrodynamics., Funding Agencies|Ion Beam Centre at Helmholtz-Zentrum Dresden-Rossendorf; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2020-05444]; Swedish Energy AgencySwedish Energy AgencyMaterials & Energy Research Center (MERC) [43611-1]; EUEuropean Commission [862721]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW 2018.0071]; UC Davis Summer GSR Award; National Science FoundationNational Science Foundation (NSF) [CAREER-2047564]; EU-FET Flagship on Quantum Technologies [820394, 820445]; European Research Council (ERC) grant SMelEuropean Research Council (ERC); Max Planck SocietyMax Planck SocietyFoundation CELLEX; German Research FoundationGerman Research Foundation (DFG) [SPP 1601, FOR 2724]; German Federal Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [16KIS0867]

Drug isomers may differ in their proarrhythmia risk. An interesting example is the drug sotalol, an antiarrhythmic drug comprising d- and l- enantiomers that both block the hERG cardiac potassium channel and confer differing degrees of proarrhythmic risk. We developed a multi-scale in silico pipeline focusing on hERG channel - drug interactions and used it to probe and predict the mechanisms of pro-arrhythmia risks of the two enantiomers of sotalol. Molecular dynamics (MD) simulations predicted comparable hERG channel binding affinities for d- and l-sotalol, which were validated with electrophysiology experiments. MD derived thermodynamic and kinetic parameters were used to build multi-scale functional computational models of cardiac electrophysiology at the cell and tissue scales. Functional models were used to predict inactivated state binding affinities to recapitulate electrocardiogram (ECG) QT interval prolongation observed in clinical data. Our study demonstrates how modeling and simulation can be applied to predict drug effects from the atom to the rhythm for dl-sotalol and also increased proarrhythmia proclivity of d- vs. l-sotalol when accounting for stereospecific beta-adrenergic receptor blocking.

В разделе сырьевая база угля для коксования описаны характеристики угольных концентратов обогатительных фабрик входящих в производственную шихту. Раздел определение размолоспособности угольных концентратов содержит описание методов определения размолоспособности угля и описан ситовый состав входящих угольных концентратов. В разделе прогнозирование качества кокса выполнен анализ засорения угольных концентратов породными и промпродуктовыми включениями, описан порядок расчетов комплексного показателя коксуемости шихт., The section raw material base of coal for coking describes the characteristics of coal concentrates of processing plants included in the production charge. The section determination of the grinding capacity of coal concentrates contains a description of methods for determining the grinding capacity of coal and describes the sieve composition of the incoming coal concentrates. In the section predicting the quality of coke, the analysis of clogging of coal concentrates with rock and industrial product inclusions is performed, and the procedure for calculating the complex coking index of the charge is described.

It is now a widely held view that, in their formation and early evolution, stars build up mass in bursts. The burst mode of star formation scenario proposes that the stars grow in mass via episodic accretion of fragments migrating from their gravitationally unstable circumstellar discs, and it naturally explains the existence of observed pre-main-sequence bursts from high-mass protostars. We present a parameter study of hydrodynamical models of massive young stellar objects (MYSOs) that explores the initial masses of the collapsing clouds (Mc = 60-200 Modot) and ratio of rotational-to-gravitational energies (β = 0.005-0.33). An increase in Mc and/or β produces protostellar accretion discs that are more prone to develop gravitational instability and to experience bursts. We find that all MYSOs have bursts even if their pre-stellar core is such that β ≤ 0.01. Within our assumptions, the lack of stable discs is therefore a major difference between low- and high-mass star formation mechanisms. All our disc masses and disc-to-star mass ratios Md/M⊙ > 1 scale as a power law with the stellar mass. Our results confirm that massive protostars accrete about 40, -, 60 percent of their mass in the burst mode. The distribution of time periods between two consecutive bursts is bimodal: there is a short duration (∼ 1, -, 10 yr) peak corresponding to the short, faintest bursts and a long-duration peak (at ∼ 103 104 yr) corresponding to the long, FU-Orionis-type bursts appearing in later disc evolution, i.e. around 30 kyr after disc formation. We discuss this bimodality in the context of the structure of massive protostellar jets as potential signatures of accretion burst history. © 2020 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society.

Luminosity bursts in young FU Orionis-type stars warm up the surrounding disks of gas and dust, thus inflicting changes on their morphological and chemical composition. In this work, we aim at studying the effects that such bursts may have on the spatial distribution of dust grain sizes and the corresponding spectral index in protoplanetary disks. We use the numerical hydrodynamics code FEOSAD, which simulates the co-evolution of gas, dust, and volatiles in a protoplanetary disk, taking dust growth and back reaction on gas into account. The dependence of the maximum dust size on the water ice mantles is explicitly considered. The burst is initialized by increasing the luminosity of the central star to 100-300 L_sun for a time period of 100 yr. The water snowline shifts during the burst to a larger distance, resulting in the drop of the maximum dust size interior to the snowline position because of more efficient fragmentation of bare grains. After the burst, the water snowline shifts quickly back to its preburst location followed by renewed dust growth. The timescale of dust regrowth after the burst depends on the radial distance so that the dust grains at smaller distances reach the preburst values faster than the dust grains at larger distances. As a result, a broad peak in the radial distribution of the spectral index in the millimeter dust emission develops at \approx 10 au, which shifts further out as the disk evolves and dust grains regrow to preburst values at progressively larger distances. This feature is most pronounced in evolved axisymmetric disks rather than in young gravitationally unstable counterparts, although young disks may still be good candidates if gravitational instability is suppressed. Abridged., Comment: Accepted for publication by Astronomy & Astrophysics

Previous observations have shown that the $\lesssim$10 au, $\gtrsim$400 K hot inner disk of the archetypal accretion outburst young stellar object, FU Ori, is dominated by viscous heating. To constrain dust properties in this region, we have performed radio observations toward this disk using the Karl G. Jansky Very Large Array (JVLA) in 2020 June-July, September, and November. We also performed complementary optical photometric monitoring observations. We found that the dust thermal emission from the hot inner disk mid-plane of FU Ori has been approximately stationary and the maximum dust grain size is $\gtrsim$1.6 mm in this region. If the hot inner disk of FU Ori which is inward of the 150-170 K water snowline is turbulent (e.g., corresponding to a Sunyaev & Shakura viscous $\alpha_{t}\gtrsim$0.1), or if the actual maximum grain size is still larger than the lower limit we presently constrain, then as suggested by the recent analytical calculations and the laboratory measurements, water-ice free dust grains may be stickier than water-ice coated dust grains in protoplanetary disks. Additionally, we find that the free-free emission and the Johnson B and V bands magnitudes of these binary stars are brightening in 2016-2020. The optical and radio variability might be related to the dynamically evolving protostellar or disk accretion activities. Our results highlight that hot inner disks of outbursting objects are important laboratories for testing models of dust grain growth. Given the active nature of such systems, to robustly diagnose the maximum dust grain sizes, it is important to carry out coordinated multi-wavelength radio observations., Comment: 27 pages, 11 figures, accepted to ApJ

We conduct simulations of the inner regions of protoplanetary disks (PPDs) to investigate the effects of protostellar magnetic fields on their long-term evolution. We use an inner boundary model that incorporates the influence of a stellar magnetic field. The position of the inner disk is dependent on the mass accretion rate as well as the magnetic field strength. We use this model to study the response of a magnetically truncated inner disk to an episodic accretion event. Additionally, we vary the protostellar magnetic field strength and investigate the consequences of the magnetic field on the long-term behavior of PPDs. We use the fully implicit 1+1D TAPIR code which solves the axisymmetric hydrodynamic equations self-consistently. Our model allows us to investigate disk dynamics close to the star and to conduct long-term evolution simulations simultaneously and includes the radial radiation transport in the stationary diffusion limit. We include stellar magnetic torques, the influence of a pressure gradient, and a variable inner disk radius in the TAPIR code to describe the innermost disk region in a more self-consistent manner and can show that this approach alters the disk dynamics considerably compared to a simplified diffusive evolution equation, especially during outbursts. The influences of a prescribed stellar magnetic field, local pressure gradients, and a variable inner disk radius result in a more consistent description of the gas dynamics in the innermost regions of PPDs. Combining magnetic torques acting on the innermost disk regions with the long-term evolution of PPDs yields previously unseen results, whereby the whole disk structure is affected over its entire lifetime. Additionally, we want to emphasize that a combination of our 1+1D model with more sophisticated multi-dimensional codes could improve the understanding of PPDs even further.

Context: The pre-main sequence evolution is often simplified by choosing classical initial models. These have large initial radii and sufficient uniform contraction to make them fully convective. Contrary to that, real stars are born as small protostellar seeds in collapsing molecular clouds and obtain their final mass by means of accretion. Aims: We aim to constrain the input physics of accretion on protostellar seeds with observed spectroscopic parameters and stellar pulsations of young stellar objects and pre-main sequence stars. Methods: We conducted a literature search for spectroscopic samples of young stellar objects and pre-main sequence stars including all previously known pulsators. The sample size of pulsating pre-main sequence stars is increased by analysing TESS observations and presenting discoveries in CoRoT data. We employ MESA and GYRE to calculate evolutionary tracks of accreting protostellar seeds in a constant accretion scenario, the subsequent pre-main sequence evolution, and their pulsation properties. The results are then compared with observations to constrain the input physics. Results: We discuss 16 formerly unknown pulsating pre-main sequence stars and candidates that are either of SPB, $\delta$ Scuti,$\gamma$ Doradus or $\delta$ Scuti - $\gamma$ Doradus hybrid type. We find that evolutionary tracks with a mass accretion rate of $5\times10^{-6} M_\odot/{\rm yr}$ and fraction of injected accretion energy of $\beta=0.1$ provide the best results in enveloping the spectroscopic parameters of pre-main sequence stars in a constant accretion scenario. The calculated instability regions constrain the atmospheric boundary conditions to Eddington Gray atmospheres; we discuss the future potential for additional constraints by instability regions that are dependent on radial order. We present a possible candidate for pulsations in M-type young stellar objects., Comment: 21 pages plus 12 for the appendix, 17 figures plus 27 for the appendix, accepted for publication in Astronomy & Astrophysics

FU Orionis-type objects (FUors) are low-mass pre-main sequence stars undergoing a temporary, but significant increase of mass accretion rate from the circumstellar disk onto the protostar. It is not yet clear what triggers the accretion bursts and whether the disks of FUors are in any way different from disks of non-bursting young stellar objects. Motivated by this, we conducted a 1.3 mm continuum survey of ten FUors and FUor-like objects with ALMA, using both the 7 m array and the 12 m array in two different configurations to recover emission at the widest possible range of spatial scales. We detected all targeted sources and several nearby objects as well. To constrain the disk structure, we fit the data with models of increasing complexity from 2D Gaussian to radiative transfer, enabling comparison with other samples modeled in a similar way. The radiative transfer modeling gives disk masses that are significantly larger than what is obtained from the measured millimeter fluxes assuming optically thin emission, suggesting that the FUor disks are optically thick at this wavelength. In comparison with samples of regular Class II and Class I objects, the disks of FUors are typically a factor of 2.9-4.4 more massive and a factor of 1.5-4.7 smaller in size. A significant fraction of them (65-70%) may be gravitationally unstable., Comment: 34 pages, 8 tables, 29 figures, accepted for publication in the Astrophysical Journal Supplement Series