State Structures Research Articles

On the Question of the Social Origins of Early Cossack Communities: Results, Methodology and Prospects of Research

Introduction. Addressing the complex and controversial problem of domestic Cossack studies – the determination of the stage affiliation of early Slavic Cossack communities – the author sets himself the task of summing up many years of discussions, identifying the most promising directions for further research, and identifying the associated methodological guidelines. Methods and materials. Many studies of the problem of the stage affiliation of early Cossack communities, carried out by pre-revolutionary, Soviet, and modern Russian Cossack researchers, as well as works on male unions and communities of the Slavic, Caucasian, and Turkic worlds, served as materials for the article. The analysis of sources and scientific publications was carried out using comparative historical and structural-functional methods, as well as methods of classification and typologization. Analysis. The available scientific papers on the problem were classified based on the social and political prototypes of early Cossack communities determined by scientists. Three groups of versions about the social nature of early Cossack communities have been identified, which correlate them: 1) with state structures; 2) with paramilitary communities that existed in the South Russian steppes and adjacent territories at the same time as the Cossacks; 3) with archaic structures (the so-called military democracy and male unions). Results. Defining the third direction as the most promising, the author of the article suggests expanding research on the cultural and historical comparison of Cossack organizations with archaic male unions and their later forms known in the Turkic, Caucasian, and Slavic worlds. We should start this case by adhering to a set of crucial methodological principles. These principles indicate that male unions were cultural universals, and their correlation with Cossack organizations may indicate not so much (and not only) genetic connections as typological ones. In contrast to the Caucasian and Central Asian unions, Cossack communities arose outside the metropolis, which, on the one hand, led to the need for them to build their own potestar structures and, on the other hand, determined the strong external impact on them from the Russian state. The development of Cossack communities did not follow the path of evolution but was first carried out in the form of a rollback to the archaic and then was associated with a series of sociocultural transformations.

Predicting ELNES/XANES spectra by machine learning with an atomic coordinate-independent descriptor and its application to ground-state electronic structures

ELNES/XANES spectra can be observed using TEM or synchrotron radiation and can elucidate the unoccupied state electronic structures of an excited states. The computation of their features is usually demanding substantial computational resources due to the requisite structure optimization and electronic structure calculations. Herein, we leverage a machine learning technique alongside an atomic-coordinate-independent descriptor, SMILES, to yield the ELNES/XANES spectra, directly, with heightened precision. Moreover, our approach extends to obtain ground state electronic structure, namely PDOS at both occupied and unoccupied ground states, underscoring its viability for a ground-state spectroscopy. Our study revealed that incorporation of long-SMILES molecules into the training dataset enhances prediction accuracy for such molecular structures. This study's direct derivation of spectroscopy from SMILES strings holds promise for expediting spectroscopic inquiries.

Accurately Predicting Barrier Heights for Radical Reactions in Solution Using Deep Graph Networks.

Quantitative estimates of reaction barriers and solvent effects are essential for developing kinetic mechanisms and predicting reaction outcomes. Here, we create a new data set of 5,600 unique elementary radical reactions calculated using the M06-2X/def2-QZVP//B3LYP-D3(BJ)/def2-TZVP level of theory. A conformer search is done for each species using TPSS/def2-TZVP. Gibbs free energies of activation and of reaction for these radical reactions in 40 common solvents are obtained using COSMO-RS for solvation effects. These balanced reactions involve the elements H, C, N, O, and S, contain up to 19 heavy atoms, and have atom-mapped SMILES. All transition states are verified by an intrinsic reaction coordinate calculation. We next train a deep graph network to directly estimate the Gibbs free energy of activation and of reaction in both gas and solution phases using only the atom-mapped SMILES of the reactant and product and the SMILES of the solvent. This simple input representation avoids computationally expensive optimizations for the reactant, transition state, and product structures during inference, making our model well-suited for high-throughput predictive chemistry and quickly providing information for (retro-)synthesis planning tools. To properly measure model performance, we report results on both interpolative and extrapolative data splits and also compare to several baseline models. During training and testing, the data set is augmented by including the reverse direction of each reaction and variants with different resonance structures. After data augmentation, we have around 2 million entries to train the model, which achieves a testing set mean absolute error of 1.16 kcal mol-1 for the Gibbs free energy of activation in solution. We anticipate this model will accelerate predictions for high-throughput screening to quickly identify relevant reactions in solution, and our data set will serve as a benchmark for future studies.

Facile C[sbnd]H aryl and O[sbnd]H bonds activation at dirhenium site of [Re2(CO)8(THF)2] complex

The activation of small molecules is a topic of great interest and previously we reported on the easy activation of different types of EH bonds at the dinuclear complex [Re2(CO)8(THF)2] (1) where labile THF molecules coordinate to adjacent rhenium(0) atoms. Here we extend the reactivity of 1 reporting on the oxidative addition of benzene and toluene at room temperature to give [Re2(μ-H)(μ-κC-Ar)(CO)8], Ar = −C6H5 (2) and −C6H4Me (3). Compound 3 is a new example of μ-κC-Ar dinuclear rhenium complex and has been obtained as para and meta isomers (3a,b). It is known from the literature that 2 can activate arenes and heteroarenes via reductive elimination of benzene and oxidative addition of CH bonds to the dinuclear fragment. Here we have studied the reaction of 2 with C6D6 and H2CC(H)Ph and determined the kinetic constants by 1H NMR (1.4 × 10−5 s−1 at 308 K and 1.1 × 10−5 s−1 at 298 K, respectively). The results indicate that the rate-determining step of the reaction is the reductive elimination of benzene, while the oxidative addition is fast. Water and methanol react with 1 in toluene at room temperature to give the hydroxo and methoxo hydrido complexes [Re2(μ-H)(μ-OR)(CO)8], RH (5) and CH3 (6). On reacting 1 with water in deuterated toluene, and monitoring by 1H/2H NMR, a preferential deuteration of the hydride site to give [Re2(μ-D)(μ-OH)(CO)8] is evidenced. This finding excludes the oxidative addition of water on the dinuclear “Re2(CO)8” fragment while supporting a heterolytic addition of water via protonation at the µ-κC-tolyl group, elimination of toluene and addition of OH−. Single crystal X-ray diffraction analyses have been performed for complexes 3a, 5 and 6 and their solid state structures have been determined. In particular, the crystal structure of 5 results in a new polymorphic form (5b) and it is discussed in comparison with the already known one (5a).

Donor-only substituted benzene achieves thermally activated delayed fluorescence

Thermally activated delayed fluorescence (TADF) is a promising mechanism for harvesting triplet excitons in organic light-emitting diodes (OLEDs). The donor–acceptor (D–A) design is the most conventional strategy for developing efficient TADF emitters. A subsequently emerged approach, known as the multiple resonance (MR) effect, also employs electron-donating and electron-withdrawing functional groups. Thus, developing TADF materials has traditionally relied on ingenuity in selecting and combining two functional units. Here, we have realized a TADF molecule by utilizing only a carbazole donor moiety. This molecule is an unusual example in the family of TADF materials and offers better insight into the electronic structures in the excited states for luminescent materials.

Prolinol‐Derived Phenoxy‐Amidine Titanium Complexes in Asymmetric Silylcyanation of Aldehydes

AbstractThree new tridentate phenoxy‐amidine ligands (FA) have been prepared via the ring‐opening of benzoxazole by 2‐(methylamino)ethanol, L‐prolinol and L‐diphenylprolinol. Coordination studies of these FA ligands with Ti have led to the synthesis of the complexes (L1–L3)Ti(OiPr)2 (1 a–3 a) and (L1–L3)TiCl2(thf) (1 b–3 b). The solid state structures of the dichlorido FA−Ti complexes revealed a distorted octahedral geometry around the metallic centre provided by the FA ligand in mer‐fashion, the two residual chloro ligands in cis arrangement and a THF molecule. The chiral Ti‐FA complexes were shown to promote the asymmetric silylcyanation reaction. With benzaldehyde as substrate, the best catalyst was the dichlorido Ti complex 3 b with a diphenylprolinol in the ligand backbone. It afforded the cyanhydrine with 68 % conversion and 74 % ee after 24 h in DCM at –20 °C. The diisopropoxy Ti complex 3 a was remarkably active with pivalaldehyde as substrate, yielding the cyanosilylated product with 99 % conversion and 61 % ee after only 30 min at −60 °C.

Analysis of prospects and problems in the development of human resources for the employment of Ukrainian refugees

An influx of workers who have accumulated knowledge in labor markets other than the current one can have particularly large effects on the development of the host country's human resources. Other things being equal, a region with higher fluctuations in the number of highly skilled workers should be in a better position than a region with low mobility. Refugee laws are in constant evolution, reflecting the changing political, economic, and legal environments. This paper examines the situation that has developed in the Czech Republic after the arrival of a large number of refugees from Ukraine, in terms of their opportunities and prospects, as well as their ability to enter the labor market in accordance with their education and previous professional activities. The purpose of this study is to analyse the potential and obstacles to the labor integration of Ukrainian refugees, given the situation of uncertainty and the measures taken by the Czech government and state structures to receive refugees. The article considers the objective and subjective prerequisites for the labor integration of refugees, taking into account their socio-demographic characteristics and subjective intentions for the future.

Mechanical performance of completely GFRP-tendon-reinforced concrete slabs considering compressive-tensile membrane action

Presently, increasingly more concrete structures strengthened with glass-fiber-reinforced polymer (GFRP) tendons have been employed in practical civil engineering owing to outstanding advantages, such as anti-corrosion, cost-effectiveness, and ease of production. These structures have demonstrated unique characteristics and mechanical response compared to steel-tendon-reinforced concrete structures in both service and ultimate load-bearing states. Therefore, in this study, to analyze completely GFRP-tendon-reinforced concrete slabs under localized wheel pressure, loading tests were conducted on two full-scale fabricated frame structures while considering the influence of membrane action on the cover slab. The mechanical response of these structures was revealed using the obtained load-displacement curves, ultimate bearing capacity, and crack morphology. The membrane action mechanism of the slab under weak lateral constraints was studied through the finite element method. The method to determine the effective membrane region of the reinforced slab was discussed and the corresponding ultimate bearing capacity was proposed considering the compressive-tensile membrane action under different failure modes. This model provides a preliminary reference for the quantitative determination of the structural properties of GFRP-tendon-reinforced concrete slabs.

Accessing the Cloke-Wilson Rearrangement via Conjugate Addition of Phosphoranes to Michael Acceptors: A Route to Cyclopropanes and 5-Membered Ring Heterocycles Investigated by Density Functional and Ab Initio Theory.

Conjugate addition of unstabilized Wittig-type phosphonium ylides to 1,1-diacceptor- and 1-acceptor-substituted alkenes is investigated by density functional theory and high-level ab initio (DLPNO-CCSD(T)) calculations. The results indicate that the initial conjugate addition step should be facile with barriers predicted to be between 0 and 21 kcal mol-1. Potential intramolecular follow-up reactions include the formation of acceptor-substituted cyclopropanes as well as the formation of dihydrofuran derivatives via intramolecular SN2-type transition state structures. The barriers calculated for these potentially valuable cyclization reactions are substantial with Gibbs free energies of activation between 19 and 40 kcal mol-1. Competing reaction channels include Wittig olefination (for ketones and aldehydes), as well as Claisen condensation reactions. The reaction offers an alternative entry point to the nucleophile-catalyzed Cloke-Wilson rearrangement.

The origin of selectivity in the trimerization of 1,3-cyclopentadiene from an activation strain perspective.

Quantum chemical modeling (DFT-PBE0/cc-pVTZ) of the [4 + 2]-cycloaddition reaction of 1,3-cyclopentadiene (CPD) to (exo/endo)-dicyclopentadiene (DCPD) was carried out, resulting in 14 products-CPD trimers. According to calculations, exo-addition of CPD to the norbornene (NB) fragment of DCPD and trans-addition of CPD to the cyclopentene (CP) fragment of DCPD are kinetically preferred. Ring strain energies ERS were calculated for all trimers using the homodesmotic reaction approach. The least strained trimers are formed by exo-addition of CPD to the NB fragment of exo-DCPD, while the most strained ones are formed by endo-addition of CPD to the NB fragment of endo-DCPD. ERS values are in good agreement with thermodynamic stability of trimers. Analysis of activation energy using the activation strain model showed steric effects causing deformation of the DCPD molecule upon reaching the transition state to be the leading factor of the magnitude of the cycloaddition reaction activation barrier. Deformation of the DCPD molecule mostly occurs in two dihedral angles-the angle of escape of H atoms from the plane of the double bond involved in cycloaddition and the angle between the NB and CP fragments. The sum of deviations of these angles in the transition states (or products) structures is in good agreement with Gibbs activation energies of cycloaddition reactions of CPD to DCPD. Quantum chemical calculations were carried out using density functional theory in Gaussian 09 software. Hybrid exchange-correlation PBE0 functional was used with cc-pVTZ basis set.

Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase.

The enzymes 3-methylcrotonyl-coenzyme A (CoA) carboxylase (MCC), pyruvate carboxylase and propionyl-CoA carboxylase belong to the biotin-dependent carboxylase family located in mitochondria. They participate in various metabolic pathways in human such as amino acid metabolism and tricarboxylic acid cycle. Many human diseases are caused by mutations in those enzymes but their structures have not been fully resolved so far. Here we report an optimized purification strategy to obtain high-resolution structures of intact human endogenous MCC, propionyl-CoA carboxylase and pyruvate carboxylase in different conformational states. We also determine the structures of MCC bound to different substrates. Analysis of MCC structures in different states reveals the mechanism of the substrate-induced, multi-element synergistic activation of MCC. These results provide important insights into the catalytic mechanism of the biotin-dependent carboxylase family and are of great value for the development of new drugs for the treatment of related diseases.

Study of political developments in democratic, communist and dictatorial systems and their impact on power, governance and human rights

In the current era, the world is experiencing profound political and economic shifts, marking a departure from the norms that dominated the pre-industrial period. Notably, the dissolution of feudal and communal systems, which were emblematic of an economy rooted in pastoral ideologies, has been underway since the French Revolution. This transformative period has not only reshaped global dynamics but also led to the reconstitution of modern state structures within the context of institutional states. This research delves into the evolving patterns of political changes and their economic repercussions in the contemporary global landscape. Our study aims to decipher the dynamics of international transformations within the global political arena and explore their interconnections with the emerging world order. Furthermore, we have endeavored to trace the philosophical political roots that underpinned these economic systems, examining their genesis and subsequent influence on political developments across various regimes, with a particular focus on implications for human rights. An analytical methodology underpins our examination of these political transformations. Central to our inquiry is the following pivotal question: What is the impact of developments in political and economic systems in the contemporary world on authority, governance, and human rights? To address this question, we deemed it necessary to discuss three topics related to political transformation, presenting an analysis for each of the following axes: 1-Circumstances and history of modern political transformations. 2-Modern political demands, compared to advanced political aspirations. 3-Human rights, between liberal propaganda and democracy. Our findings reveal that political variables have undergone substantial changes that significantly influence political ideologies, the conceptualization of authority, and human rights considerations. Among these influential factors are: Globalization and Technology: Technological advancements and the expansion of global communications via the Internet have opened new avenues for political discourse and interaction. This development transcends local boundaries, positioning politics as a globally interconnected phenomenon. Social and Cultural Transformations: There has been a significant shift in social and cultural paradigms, particularly in the heightened awareness of human rights. This shift has broadened the scope of political thought and necessitated the integration of these issues into both national and international political dialogues. Economic Transformations: The evolution of economic structures, spurred by technological progress and globalization, has profound implications for political theories concerning the equitable distribution of wealth, economic opportunities, poverty alleviation, and addressing economic disparities.

ADMINISTRATIVE AND LEGAL GUIDELINES FOR STANDARDIZATION OF FINANCIAL REPORTING OF ENTERPRISES AS SOCIO-ECONOMIC SYSTEMS

This article aims to present an approach for determining the most effective administrative and legal guidelines for the standardization of financial reporting in modern open socio-economic systems. It emphasizes the current state of financial reporting of these open socio-economic systems at the time of analysis and the application of the proposed approach. As the most common form of open socio-economic systems today, enterprises are taken as the basis. The method of multi-criteria decision analysis (MCDA), which encompasses various approaches to decision-making based on multiple criteria, including hierarchical analysis, was applied. In addition to its comprehensiveness, the method of pairwise comparison, which involves the use of two elements for comparison, was also applied. Experts were involved in the assessment and determination of the administrative and legal guidelines. As a result, an approach to forming key administrative and legal guidelines for the standardization of financial reporting was developed, which, unlike other similar approaches, aims to take into account external environmental factors and the changes they bring in order to try to adjust financial reporting standardization policies in complex development conditions. The practical value is revealed in the possibility of application by state bodies and structures involved in the development and establishment of financial reporting standards in Ukraine.

Первый храм в Челябинской крепости в контексте сакрализации пространства в ходе русской колонизации Урала и Сибири

The first temple in the Chelyabinsk fortress in the context of the sacralization of space during the Russian colonization of the Urals and Siberia.The article, on the basis of the sources involved, deals in general terms with the main problems of temple building in the frontier zone in the process of Russian colonization of the Urals and Siberia from the late XVI to the 1730s. Sources are acts of record documentation: decrees, orders, reports. The purpose of the article is to analyze the relationship between state and church structures in temple building. The work is done within the framework of cultural history.The main institutions of the colonization process were the structures of the state and the church, the direct actors were peasants, merchants and servicemen of various categories, and the Posad population. The consolidation of Russia in new territories was carried out through the sacralization of space. The starting point in this process was the construction of the first Orthodox church. Initially, the question of building a temple was raised by both the secular authorities and parishioners, depending on the specific situation. Then the functions of establishing the ecclesiastical and administrative structure were delegated by the center to the field.If earlier the chain looked like this: Orthodox first settlers - the center in Moscow - the royal decree in place of the voivode - implementation, execution of the decision on the spot; then a new link appears at the diocesan level in the person of the bishop. This was caused, first of all, by the increasing scale of colonization, the complication of the secular and ecclesiastical-administrative structure. In the record correspondence, the idea of the impossibility of the existence of an Orthodox person without a temple can be traced.To find out the initiators of the nomination of the first temple in the Chelyabinsk fortress, an analysis of the names of the bishops of the Siberian Metropolis, in charge of which the fortress was located, was undertaken; monks of the Assumption Dalmatian Monastery in 1735, whose archimandrite was instructed to lay the church; the heads of the families of the fortress, recorded in the census of 1739 – 1740. From this it was concluded that the "symphony" of the initiative "from above" and the initiative "from below" was made.

Dynamically Tunable Circularly Polarized Selectivity in Plasmon-Enhanced Halide Perovskite Nanocrystal Glasses.

Ultrafast spin manipulation for optical spin-logic applications requires material systems with strong spin-selective light-matter interactions. The optical Stark effect can realize spin-selective light-matter interactions by breaking the degeneracy of spin-selective transitions with an external electric field. Halide perovskites have large exciton binding energies, which enable a room-temperature optical Stark effect. However, halide perovskites are prone to degradation when interacting with light and polar solvents, limiting further integration with nanophotonic structures. We demonstrate a hybrid material system consisting of CsPbBr3 nanocrystal glass weakly coupled to resonant plasmonic silver nanoparticles, showing ultrafast tunable spin-based polarization selectivity at room temperature. We performed circularly polarized pump-probe characterizations to investigate the optical Stark effect in this material system, which resulted in a maximum energy shift of ∼3.67 meV (detuning energy of 0.11 eV and pump intensity of 0.62 GW/cm2). We show that halide perovskite nanocrystal glasses have excellent resistance to heat and moisture, which may be favorable for integration with nanophotonic structures for further engineering polarization states, energy tuning, and coherence time.

To justification of concrete strength criterion at biaxial compression

Introduction. Numerous experimental data from Russian and foreign researchers indicate that the classical plasticity hypotheses do not take into account the different resistance to uniaxial tension and compression, the influence of the spherical tensor. At the same time, experiments show that the ultimate resistance depends on the type of stress state, and hydrostatic pressure increases the strength and plasticity of solids. Aim. To establish the dependence of the influence of the second component of stresses during biaxial compression of concrete on the parameters of the complete diagrams of deformation of the material σbR and εbR it is necessary to describe these diagrams, and to construct a closed curve on the plane of the main stresses (concrete strength criterion). Materials and methods. Based on the experimental materials of foreign and domestic researchers, including the experiments of the authors of the article, methods of mechanics of deformed solids, limit curves and a closed curve on the plane of the main stresses in the form of a chain line forming the smallest area strength surface in the form of a catenoid are proposed. Results. The article provides an analysis of the known strength criteria from the point of view of their geometric interpretation in the stress space. It is shown that these studies relate mainly to metals and metal structures, and for the design of reinforced concrete and steel-concrete structures in a complex stress state, it is necessary to develop an appropriate criterion for the strength of concrete. Conclusions. As a result, the proposed limit curves and the surface (material strength criterion) on the plane of main stresses in the form of a catenoid accurately reflect the behavior of concrete under conditions of uniform and uneven flat stress state, and the equation of the surface in the form of a catenoid is a generalization of the equations of limit curves for each of the three types of flat stress state. At the same time, there is no overestimation of strength in the "compression – compression" area in this case.

Structural insights into the diversity and DNA cleavage mechanism of Fanzor

Fanzor (Fz) is an ωRNA-guided endonuclease extensively found throughout the eukaryotic domain with unique gene editing potential. Here, we describe the structures of Fzs from three different organisms. We find that Fzs share a common ωRNA interaction interface, regardless of the length of the ωRNA, which varies considerably across species. The analysis also reveals Fz's mode of DNA recognition and unwinding capabilities as well as the presence of a non-canonical catalytic site. The structures demonstrate how protein conformations of Fz shift to allow the binding of double-stranded DNA to the active site within the R-loop. Mechanistically, examination of structures in different states shows that the conformation of the lid loop on the RuvC domain is controlled by the formation of the guide/DNA heteroduplex, regulating the activation of nuclease and DNA double-stranded displacement at the single cleavage site. Our findings clarify the mechanism of Fz, establishing a foundation for engineering efforts.

Structures of multiple states of the nicotinamide nucleotide transhydrogenase from Escherichia coli

Structures of multiple states of the nicotinamide nucleotide transhydrogenase from Escherichia coli

Insights from Ca2+→Sr2+ substitution on the mechanism of O-O bond formation in photosystem II.

In recent years, there has been a steady interest in unraveling the intricate mechanistic details of water oxidation mechanism in photosynthesis. Despite the substantial progress made over several decades, a comprehensive understanding of the precise kinetics underlying O-O bond formation and subsequent evolution remains elusive. However, it is well-established that the oxygen evolving complex (OEC), specifically the CaMn4O5 cluster, plays a crucial role in O-O bond formation, undergoing a series of four oxidative events as it progresses through the S-states of the Kok cycle. To gain further insights into the OEC, researchers have explored the substitution of the Ca2+ cofactor with strontium (Sr), the sole atomic replacement capable of retaining oxygen-evolving activity. Empirical investigations utilizing spectroscopic techniques such as XAS, XRD, EPR, FTIR, and XANES have been conducted to probe the structural consequences of Ca2+→Sr2+ substitution. In parallel, the development of DFT and QM/MM computational models has explored different oxidation and protonation states, as well as variations in ligand coordination at the catalytic center involving amino acid residues. In this review, we critically evaluate and integrate these computational and spectroscopic approaches, focusing on the structural and mechanistic implications of Ca2+→Sr2+ substitution in PS II. We contribute DFT modelling and simulate EXAFS Fourier transforms of Sr-substituted OEC, analyzing promising structures of the S3 state. Through the combination of computational modeling and spectroscopic investigations, valuable insights have been gained, developing a deeper understanding of the photosynthetic process.

Concentration effect of zinc ions on amyloid fibrillation of hen egg-white lysozyme with thermal treatment revealed by Raman spectroscopy

Accumulation of Zn2+ ions in protein aggregates has been suggested to be a key factor in Alzheimer’s disease etiology. However, the specific influence of Zn2+ ions on the formation of amyloid fibrils or amorphous aggregates is still much debated. Herein, we conducted a combined study of Raman spectroscopy, UV–vis absorption spectroscopy and ThT fluorescence assay on the concentration effects of Zn2+ ions on amyloid fibrillation of hen egg-white lysozyme with thermal treatment. The addition of Zn2+ ions showed a negligible effect on unfolding of the protein tertiary structures and nucleation pathways on amyloid fibrillation. In contrast, a distinct concentration-dependence was observed for the influence of Zn2+ ions on the transformation of lysozyme secondary structures. At low concentration, the metal ions do not affect the populations of major secondary structures in the final state after incubation, while they at high concentration exhibit a promotion effect on the transformation from α-helix to β-sheet-like structures. These findings provide insights into the multifaceted impact of Zn2+ ions on protein aggregation, shedding light on potential therapeutic strategies for neurodegenerative diseases.