Free States Research Articles

Specifying conformational heterogeneity of multi-domain proteins at atomic resolution

The conformational landscape of multi-domain proteins is inherently linked to their specific functions. This also holds for polyubiquitin chains that are assembled by two or more ubiquitin domains connected by a flexible linker thus showing a large interdomain mobility. However, molecular recognition and signal transduction are associated with particular conformational substates that are populated in solution. Here, we apply high-resolution NMR spectroscopy in combination with dual-scale MD simulations to explore the conformational space of K6-, K29-, and K33-linked diubiquitin molecules. The conformational ensembles are evaluated utilizing a paramagnetic cosolute reporting on solvent exposure plus a set of complementary NMR parameters. This approach unravels a conformational heterogeneity of diubiquitins and explains the diversity of structural models that have been determined for K6-, K29-, and K33-linked diubiquitins in free and ligand-bound states so far. We propose a general application of the approach developed here to demystify multi-domain proteins occurring in nature.

Quantifying the phase of quantum states

Phase is a basic ingredient for quantum states since quantum mechanics uses complex numbers to describe quantum states. In this work, we introduce a rigorous framework to quantify the phase of quantum states. To do so, we regard phase as a quantum resource, and specify the free states and free operations. We determine the conditions a phase measure should satisfy and provide some phase measures. We also propose the notion of intrinsic phase for quantum states.

NMR-Chemical-Shift-Driven Protocol Reveals the Cofactor-Bound, Complete Structure of Dynamic Intermediates of the Catalytic Cycle of Oncogenic KRAS G12C Protein and the Significance of the Mg2+ Ion.

In this work, catalytically significant states of the oncogenic G12C variant of KRAS, those of Mg2+-free and Mg2+-bound GDP-loaded forms, have been determined using CS-Rosetta software and NMR-data-driven molecular dynamics simulations. There are several Mg2+-bound G12C KRAS/GDP structures deposited in the Protein Data Bank (PDB), so this system was used as a reference, while the structure of the Mg2+-free but GDP-bound state of the RAS cycle has not been determined previously. Due to the high flexibility of the Switch-I and Switch-II regions, which also happen to be the catalytically most significant segments, only chemical shift information could be collected for the most important regions of both systems. CS-Rosetta was used to derive an "NMR ensemble" based on the measured chemical shifts, which, however, did not contain the nonprotein components of the complex. We developed a torsional restraint set for backbone torsions based on the CS-Rosetta ensembles for MD simulations, overriding the force-field-based parametrization in the presence of the reinserted cofactors. This protocol (csdMD) resulted in complete models for both systems that also retained the structural features and heterogeneity defined by the measured chemical shifts and allowed a detailed comparison of the Mg2+-bound and Mg2+-free states of G12C KRAS/GDP.

Diverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S

Context-dependent dynamic histone modifications constitute a key epigenetic mechanism in gene regulation1–4. The Rpd3 small (Rpd3S) complex recognizes histone H3 trimethylation on lysine 36 (H3K36me3) and deacetylates histones H3 and H4 at multiple sites across transcribed regions5–7. Here we solved the cryo-electron microscopy structures of Saccharomyces cerevisiae Rpd3S in its free and H3K36me3 nucleosome-bound states. We demonstrated a unique architecture of Rpd3S, in which two copies of Eaf3–Rco1 heterodimers are asymmetrically assembled with Rpd3 and Sin3 to form a catalytic core complex. Multivalent recognition of two H3K36me3 marks, nucleosomal DNA and linker DNAs by Eaf3, Sin3 and Rco1 positions the catalytic centre of Rpd3 next to the histone H4 N-terminal tail for deacetylation. In an alternative catalytic mode, combinatorial readout of unmethylated histone H3 lysine 4 and H3K36me3 by Rco1 and Eaf3 directs histone H3-specific deacetylation except for the registered histone H3 acetylated lysine 9. Collectively, our work illustrates dynamic and diverse modes of multivalent nucleosomal engagement and methylation-guided deacetylation by Rpd3S, highlighting the exquisite complexity of epigenetic regulation with delicately designed multi-subunit enzymatic machineries in transcription and beyond.

SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic Nanomaterials.

ConspectusWhen the size of materials is reduced, their volume decreases much faster than their surface area, which in the most extreme case leads to 2D nanomaterials which are "all surface". Since atoms at the surface have free energies, electronic states, and mobility which are very different from bulk atoms, nanomaterials that have large surface-to-volume ratios can display remarkable new properties compared to their bulk counterparts. More generally, the surface is where nanomaterials interact with their environment, which in turn places surface chemistry at the heart of catalysis, nanotechnology, and sensing applications. Understanding and utilizing nanosurfaces are not possible without appropriate spectroscopic and microscopic characterization techniques. An emerging technique in this area is surface-enhanced Raman spectroscopy (SERS), which utilizes the interaction between plasmonic nanoparticles and light to enhance the Raman signals of molecules near the nanoparticles' surfaces. SERS has the great advantage that it can provide detailed in situ information on surface orientation and binding between molecules and the nanosurface. A long-standing dilemma that has limited the applications of SERS in surface chemistry studies is the choice between surface-accessibility and plasmonic activity. More specifically, the synthesis of metal nanomaterials with strong plasmonic and SERS-enhancing properties typically involves the use of strongly adsorbing modifier molecules, but these modifiers also passivate the surface of the product material, which prevents the general application of SERS in the analysis of weaker molecule-metal interactions.In this Account, we discuss our efforts in the development of modifier-free synthetic approaches to synthesize surface-accessible, plasmonic nanomaterials for SERS. We start by discussing the definition of "modifiers" and "surface-accessibility", especially in the context of surface chemistry studies in SERS. As a general rule of thumb, the chemical ligands on surface-accessible nanomaterials should be easily displaceable by a wide range of target molecules relevant to potential applications. We then introduce modifier-free approaches for the bottom-up synthesis of colloidal nanoparticles, which are the basic building blocks for nanotechnology. Following this, we introduce modifier-free interfacial self-assembly approaches developed by our group that allow the creation of multidimensional plasmonic nanoparticle arrays from different types of nanoparticle-building blocks. These multidimensional arrays can be further combined with different types of functional materials to form surface-accessible multifunctional hybrid plasmonic materials. Finally, we demonstrate applications for surface-accessible nanomaterials as plasmonic substrates for SERS studies of surface chemistry. Importantly, our studies revealed that the removal of modifiers led to not only significantly enhanced properties but also the observation of new surface chemistry phenomena that had been previously overlooked or misunderstood in the literature. Realizing the current limitations of modifier-based approaches provides new perspectives in manipulating molecule-metal interactions in nanotechnology and can have significant implications in the design and synthesis of the next generation of nanomaterials.

INTERNATIONAL POLITICAL DIALOGUE AS THE BASIS OF UKRAINE'S INTEGRATION INTO THE EU

The category "international political dialogue" is considered, which should be understood as a political-psychological and political-legal decision-making process by harmonizing the positions of states on complex problems and ensuring the process of their implementation. The most important prerequisites for interstate dialogue are the equality of the parties. The mutual interest of Ukraine and the European Union regarding the integration movement of Ukraine into the EU, which is the choice of the Ukrainian people, is emphasized. The main state documents that ensure this movement are considered. Since the EU is an integration entity of developed free and democratic states, it strives precisely for parity dialogue. In the conditions of globalization of socio-political development, political crisis, in particular, war, it is impossible to obtain EU membership without reaching a consensus on certain problematic issues and implementing the results of international political dialogue. The dictation of one party and/or the lack of willingness to negotiate excludes the existence of dialogue, as the agreement of the parties' positions is replaced by unilateral or multilateral (depending on the situation) pressure. Attention is paid to the complex process of ensuring political dialogue with a number of special measures (from defining the goal, resolving conflict situations to reaching the desired consensus). It was revealed that the obstacles to the effective political dialogue of Ukraine with the EU are the problems that the latter emphasizes: ineffective fight against corruption, slow reform of the law enforcement system, involvement of the judiciary; imperfection of the legal framework; uncompetitiveness of the financial system and the banking sector; weak protection of property rights of a potential investor.

A Two-Species Finite Volume Scalar Model for Modeling the Diffusion of Poly(lactic-co-glycolic acid) into a Coronary Arterial Wall from a Single Half-Embedded Drug Eluting Stent Strut

This paper outlines the methodology and results for a two-species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA)) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two-species (free-drug and bound-drug) mass transport setup, including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of the drug between the free and bound-drug states. The model is solved by a 2D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over previously developed models using the finite-difference and finite element method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying the polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 h (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug.

Accelerated aging behavior and degradation mechanism of nitrile rubber in thermal air and hydraulic oil environments

AbstractThe aging behavior and degradation mechanism of nitrile rubber (NBR) under free and compression states were investigated in simulated air and hydraulic oil environments at various elevated temperatures. The variations in the crosslinking density, volatile components and the chemical structure of NBR during aging were studied using equilibrium swelling testing and dynamic mechanical analysis (DMA), pyrolysis‐gas chromatography–mass spectrometry and attenuated total reflection‐Fourier transform infrared spectroscopy. The migration of additives in different media and the crosslinking density of NBR aged in different conditions were compared. The tensile strength, DMA, and thermogravimetric analysis results were consistent with the changes in the crosslinking density of NBR and the migration of additives. Four effects of the simulated hydraulic system on the thermal aging of NBR were examined. Both the compression stress and the oil medium slowed the aging of NBR. The results can provide new insights into the use of NBR products in lubricating oil environments and NBR lifespan prediction in hydraulic working conditions.

Gravitation-induced temperature of single atoms on atomic and cosmological scales

The experimental findings on the rate of transfer of a single Xe atom from the sample surface towards the tip in the low temperature STM, induced by voltage pulses, are understood by assuming a vibrational temperature for a single Xe atom. But temperature is introduced in standard quantum physics as a parameter in the Boltzmann distribution of a statistical ensemble consisting of large number of non-interacting exact copies of the dynamical system under investigation. This represents a problem, if the system under investigation is to be described by a single pure quantum state being a solution of Schrödinger’s equation. In the framework of a quantum field theory based on Einstein-Hilbert action in high dimensions (EHHD) we demonstrate that temperature for a single atom emerges if the atom is beabled in a warp resonance due to entanglement with local gravitons (gravonons), living in high spacetime dimensions (11D). Desorbing Xe atom in a limbo state in the tunnel gap, due to destruction of the beable via inelastic tunnelling, is in Boltzmann distribution over plane waves {| k〉} since the squared overlap of the warp resonance with free plane wave states varies like exp(–Ek/kBTvib ) where Ek is the energy of the free particle state and Tvib is the vibrational temperature of Xe calculated from the shape and the extension of the warp resonance. The nature of the warp resonance varies with the tip-sample voltage (becoming more contracted at higher tunnelling currents, as the tip approaches the sample) and raises its energy to higher values. More contracted warps at higher tunnelling currents imply stronger overlap with free states of higher energy, described by Boltzmann factors of higher temperature. The mechanism generating single atom temperature generalizes to other dynamical processes where temperature is completely determined by the nature of the warp resonance in the beables. For homogeneous and isotropic systems this implies a universal value of the temperature everywhere in the system. With these considerations the mechanism is also applied to intergalactic hydrogen-atom clusters, where it explains the observed temperature of the CMB radiation and the absence of the horizon problem.

The kinetic Hamiltonian with position-dependent mass

In the present paper we examine in a systematic way the most relevant orderings of pure kinetic Hamiltonians for five different position-dependent mass (PDM) profiles: soliton-like, reciprocal quadratic and biquadratic, exponential and parabolic. As a result of the non-commutativity between momentum and position operators, a diversity of effective potentials is generated. We analyze the whole set and find unexpected coincidences as well as discrepancies among them. We obtain analytically the full-spectrum of energies and solutions in the twenty-five cases considered. It is shown how the simple ordinary constant-mass solutions are transformed into a variety of complex combinations of transcendental functions and arguments. We find that particles with a non-uniform mass density can present discrete energy spectra as well as continuous ones which can be bounded or not. These results are consistent with the fact that although the external potential is zero, PDM eigenfunctions are not actual free states but a sort of effective waves in a solid-state sample. This is precisely the origin of the position-dependent mass. In all the events we obtain exact complete spectral expressions. Our methodological procedure thus puts a wide diversity of Hamiltonian seeds on an equal footing in order to be compared. This allows choosing the better arrangement to model a specific solid or heterostructure once the spectrum of a given material is experimentally available. Finally, we perform a one-dimensional model calculation of a double heterostructure with a parabolic PDM particle in the interface region. Our study is also indicated for applications inside material structures with the addition of external potentials.

A labeled dataset for building HVAC systems operating in faulted and fault-free states

Open data is fueling innovation across many fields. In the domain of building science, datasets that can be used to inform the development of operational applications - for example new control algorithms and performance analysis methods - are extremely difficult to come by. This article summarizes the development and content of the largest known public dataset of building system operations in faulted and fault free states. It covers the most common HVAC systems and configurations in commercial buildings, across a range of climates, fault types, and fault severities. The time series points that are contained in the dataset include measurements that are commonly encountered in existing buildings as well as some that are less typical. Simulation tools, experimental test facilities, and in-situ field operation were used to generate the data. To inform more data-hungry algorithms, most of the simulated data cover a year of operation for each fault-severity combination. The data set is a significant expansion of that first published by the lead authors in 2020.

Continuity of robustness measures in quantum resource theories

Robustness measures are increasingly prominent resource quantifiers that have been introduced for quantum resource theories such as entanglement and coherence. Despite the generality of these measures, their usefulness is hindered by the fact that some of their mathematical properties remain unclear, especially when the set of resource-free states is non-convex. In this paper, we investigate continuity properties of different robustness functions. We show that their continuity depends on the shape of the set of free states. In particular, we demonstrate that in many cases, star-convexity is sufficient for Lipschitz-continuity of the robustness, and we provide specific examples of sets leading to non-continuous measures. Finally, we illustrate the applicability of our results by defining a robustness of teleportability and of quantum discord.

Terrorism and the most dangerous threat to the whole world: current issues

Unfortunately, nowadays the general public and the world at large are going through high level of risk and dangerous due to a terrible threat of nuclear weapons as well as weapons of mass destruction. Here, the point is the pretending nuclear wars do not limit between only two parties or states, but goes far, might go to every single country which leads to the third world war, existence of humanity is under annihilation. In past decades societies in general thought only terrorists do terrorism, besides some countries which support radical groups and use them in secret, but now the situation is changed, the recognized states and countries announce frankly to use nuclear or mass destruction weapons, not just that but, becomes a title of their bulletin news which is in fact a dangerous precedent on the ground. The current situation is in the highest alarm and only a simple start with a spark by a conflict or non-conflict parties on the ground which goes under control and the whole world suffers from it. The world community has already had the bitterness and mass destroying of using nuclear weapon, but unfortunately it shows that not all states took the seriousness of humanitarian catastrophe after using nuclear weapon yet. It means any using of the mass destruction weapons will almost the end of living on the earth as the experts imagine and analyze how the case goes worse and worse day after day, even the international relationship in all aspects of diplomatic, economic, trade and other fields are deteriorated and not as before because of having desire by some states to occupy and takeover of other territories or free states under different names and non-logic reasons and that’s why almost all states try to rebuild its army and expense more and more money on its army and weapons. This threat is like a plague thus, if we do not have a medicine and solution it wipes out an entire population without any exception among countries whether the country is superpower or non-superpower including the permanent members of Security Council of United Notion. Hence, the article is based on said statements issued by high rank officials and other facts research.

Attainability and Lower Semi-continuity of the Relative Entropy of Entanglement and Variations on the Theme

The relative entropy of entanglement E_R is defined as the distance of a multipartite quantum state from the set of separable states as measured by the quantum relative entropy. We show that this optimisation is always achieved, i.e. any state admits a closest separable state, even in infinite dimensions; also, E_R is everywhere lower semi-continuous. We use this to derive a dual variational expression for E_R in terms of an external supremum instead of infimum. These results, which seem to have gone unnoticed so far, hold not only for the relative entropy of entanglement and its multipartite generalisations, but also for many other similar resource quantifiers, such as the relative entropy of non-Gaussianity, of non-classicality, of Wigner negativity—more generally, all relative entropy distances from the sets of states with non-negative lambda -quasi-probability distribution. The crucial hypothesis underpinning all these applications is the weak*-closedness of the cone generated by free states, and for this reason, the techniques we develop involve a bouquet of classical results from functional analysis. We complement our analysis by giving explicit and asymptotically tight continuity estimates for E_R and closely related quantities in the presence of an energy constraint.

Compact, easy-accessible and tunable double injection micro-ring element for real-time spectral reshaping

To realize the compact and easy-accessible performance of the programmable multipurpose photonic integrated circuits, a tunable double injection micro-ring element on the silicon-on-insulator (SOI) platform is proposed in this paper. The element possesses an inherent property that can provide two free spectral range states for only one single ring length. Reconfigurability and programmability can be realized by modulating a specific group of parameters, including coupling coefficients, phase difference, and power splitting ratio. Various spectra are experimentally demonstrated and characterized at wavelengths around 1550 nm, such as rectangular, tangent-like, bandpass, and so on. By taking the advantage of the SOI platform, the power consumption and footprint are improved compared to schemes with similar configurations.

Pore-scale modelling of water sorption in nanopore systems of shale

Water vapor sorption in nanoporous media with complex pore structures, like shale, is not well understood. To address this, a pseudopotential lattice Boltzmann method (LBM) is developed to investigate water sorption behavior. The LBM model incorporates long-range molecular forces using a modified Shan-Chen model based on the Carnahan-Starling equation of state. The simulation results show that the presence of water films in nanopores can create a liquid pressure difference of up to 100 MPa between confined and free states. The adsorption theories based on simple pore shapes are not applicable to nanoporous systems with complex pore geometries. Additionally, when the relative humidity exceeds 1, water vapor condenses inside hydrophobic nanostructures while being attracted by neighboring liquid, leading to cluster formation. In water-wet nanoporous media, capillary condensation occurs progressively from small throats to large pores, and the sorption curves vary smoothly with pressure variation. In mixed-wet nanoporous media, the sorption curves exhibit no hysteresis in the early desorption stage, where the adsorption and desorption processes occur in the region around the hydrophobic particles and are reversible. Overall, this study provides valuable insights into water sorption behavior in nanopore systems of shale and sets the foundation for modelling liquid-vapor distribution in nanoporous media at the pore scale.

Epigenetic switching with asymmetric bridging interactions

Gene expression states are often stably sustained in cis despite massively disruptive events like DNA replication. This is achieved by on-going enzymatic activity that maintains parts of the DNA in either heterochromatic (packed) or euchromatic (free) states, each of which is stabilized by both positive feedback and bridging interactions between individual nucleosomes. In contrast to condensed matter, however, the dynamics is not only governed by equilibrium binding interactions but is also mediated by enzymes that recognize and act on specific amino acid tails of the nucleosomes. The mechanical result is that some nucleosomes can bind to one another and form tightly packed polymer configurations, whereas others remain unbound and form free, noncompact polymer configurations. Here, we study the consequences of such an asymmetric interaction pattern on the dynamics of epigenetic switching. We develop a 3D polymer model and show that traits associated with epigenetic switching, such as bistability and epigenetic memory, are permitted by such a model. We find, however, that the experimentally observed burst-like nature of some epigenetic switches is difficult to reproduce by this biologically motivated interaction. Instead, the behavior seen in experiments can be explained by introducing partial confinement, which particularly affects the euchromatic regions of the chromosome.

Quantitative characterization of shale pore connectivity and controlling factors using spontaneous imbibition combined with nuclear magnetic resonance T2 and T1-T2

Shale oil can be extracted from shale by using interconnected pore networks. The migration of hydrocarbon molecules within the shale is controlled by pore connectivity. However, assessing the pore connectivity of shale oil reservoirs is uncommon. To characterize pore connectivity and clarify its controlling factors, this study used spontaneous imbibition (SI) combined with nuclear magnetic resonance (NMR) T2 and T1-T2 technologies on shale oil reservoirs selected from the Shahejie Formation in the Dongying Sag, Bohai Bay Basin. According to the findings, the SI processes of shales include fast-rising, slow-rising, and stable stages. The fast-rising stage denotes pore connectivity. The shales studied have poor connectivity, with lower imbibition slopes and connected porosity ratios, but large effective tortuosity. During the SI process, micropores have the highest imbibition saturation, followed by mesopores and macropores. Furthermore, n-dodecane ingested into micropores appears primarily as adsorbed, whereas n-dodecane appears primarily as free states in mesopores and macropores during the SI process. The pore connectivity of the shales under study is primarily controlled by inorganic minerals. Quartz and feldspar develop large and regular pores, resulting in better pore connectivity, whereas clay minerals and calcite with plenty of complex intragranular pores do not. Organic matter negatively influences pore connectivity because the dissolution of calcite by organic acid produced during hydrocarbon generation leads to a more complex and heterogeneous pore structure. This study sheds light on the pore connectivity and controlling factors of the shale oil reservoir and aids in the understanding of shale oil mobility.

Continuum of Bound States in a Non-Hermitian Model.

In a Hermitian system, bound states must have quantized energies, whereas free states can form a continuum. We demonstrate how this principle fails for non-Hermitian systems, by analyzing non-Hermitian continuous Hamiltonians with an imaginary momentum and Landau-type vector potential. The eigenstates, which we call "continuum Landau modes" (CLMs), have Gaussian spatial envelopes and form a continuum filling the complex energy plane. We present experimentally realizable 1D and 2D lattice models that host CLMs; the lattice eigenstates are localized and have other features matching the continuous model. One of these lattices can serve as a rainbow trap, whereby the response to an excitation is concentrated at a position proportional to the frequency. Another lattice can act a wave funnel, concentrating an input excitation onto a boundary over a wide frequency bandwidth. Unlike recent funneling schemes based on the non-Hermitian skin effect, this requires a simple lattice design with reciprocal couplings.

Formation of an Extended Quantum Dot Array Driven and Autoprotected by an Atom-Thick h-BN Layer.

Engineering quantum phenomena of two-dimensional nearly free electron states has been at the forefront of nanoscience studies ever since the first creation of a quantum corral. Common strategies to fabricate confining nanoarchitectures rely on manipulation or on applying supramolecular chemistry principles. The resulting nanostructures do not protect the engineered electronic states against external influences, hampering the potential for future applications. These restrictions could be overcome by passivating the nanostructures with a chemically inert layer. To this end we report a scalable segregation-based growth approach forming extended quasi-hexagonal nanoporous CuS networks on Cu(111) whose assembly is driven by an autoprotecting h-BN overlayer. We further demonstrate that by this architecture both the Cu(111) surface state and image potential states of the h-BN/CuS heterostructure are confined within the nanopores, effectively forming an extended array of quantum dots. Semiempirical electron-plane-wave-expansion simulations shed light on the scattering potential landscape responsible for the modulation of the electronic properties. The protective properties of the h-BN capping are tested under various conditions, representing an important step toward the realization of robust surface state based electronic devices.