State Interactions Research Articles

Prediction of Successful Amorphous Solid Dispersion Pairs through Liquid State Nuclear Magnetic Resonance.

Amorphous solid dispersions (ASDs) function in part via a "parachute effect", i.e., polymer-enabled prolonged drug supersaturation, presumably through drug-polymer interactions in the liquid state. We aim to expand the utility of liquid state nuclear magnetic resonance (1HNMR) to streamline polymer selection for ASDs. Our hypothesis is that strong molecular interactions between polymer and drug in 1HNMR anticipate reduced precipitation kinetics in supersaturation studies. For three drug-polymer pairs (i.e., etravirine with each HPMC, HPMCAS-M, and PVP-VA), 1HNMR findings were compared to more common supersaturation studies. Drug-polymer interactions were assessed by saturation transfer difference NMR (STD-NMR) and T1 relaxation time. 2D-1H NOESY experiments were also performed. Supersaturation studies involved precipitation inhibition using the solvent-shift methodology. The results from STD-NMR and T1 relaxation time indicate etravirine bound preferably to HPMCAS-M > HPMC ≫ PVP-VA. STD-NMR and T1 relaxation time yielded insight into which fragments of etravirine structure bind with HPMCAS-M and HPMC. The strong interactions from STD-NMR and T1 relaxation time changes indicated that HPMCAS-M and HPMC, but not PVP-VA, are suitable polymers to maintain etravirine supersaturation and inhibit drug precipitation. 2D-1H NOESY results corroborate the findings of STD-NMR and T1 relaxation time, showing that etravirine interacts preferably to HPMCAS-M than to PVP-VA. Supersaturation studies using solvent-shift technique corroborated our hypothesis as predissolved HPMCAS-M and HPMC, but to a less extent PVP-VA, markedly promoted etravirine supersaturation and inhibited drug precipitation. Supersaturation studies agreed with STD-NMR and T1 relaxation time predictions, as HPMC and HPMCAS-M maintained etravirine in solution for longer time than PVP-VA. The results show promise of 1HNMR to streamline polymer selection in a nondestructive and resource sparing fashion for subsequent ASD development.

Exploring Charge Transfer Mechanisms in Schiff Base‐Modified N‐Doped GQDs: Insights from DFT and Pump‐Probe Spectroscopy for Bioimaging Applications

AbstractIn recent developments, graphene quantum dots (GQDs) have emerged as valuable tools for imaging and biosensing. Various modifications on the GQDs with any desired functionality and attachment of organic molecules and/or nanostructures allow tuning their photophysical properties as well as charge transfer dynamics for bioimaging applications. This study focuses on synthesizing and characterizing of polyethyleneimine‐functionalized nitrogen‐doped GQDs (NC1), Schiff base‐ functionalized nitrogen‐doped GQDs (NC2), and silver nanocomposites of these Schiff base‐functionalized nitrogen‐doped GQDs (NC3). We explore their absorption and emission properties to understand their interactions in the ground state. Furthermore, ultrafast transient absorption spectroscopy measurements reveal that the presence of NC3 shortens the excited state lifetime of NC1 due to charge transfer, resulting in reduced fluorescence intensity. Both experimental and DFT results suggest the potential of NC3 for bioimaging and sensing applications, making them promising candidates for phototheranostic purposes.

Face-to-Face Gold Porphyrins.

The interaction of square-planar metal complexes through space is of fundamental interest and relevant for the potential cooperative catalysis of two metal complex sites. In order to elucidate gold/gold, gold/porphyrin, and porphyrin/porphyrin interactions in the formal oxidation states +III and +II (after reduction) and in the excited triplet state after light excitation, a Pacman bis(gold(III)) complex [Au2(DPD)][PF6]2 with square-planar face-to-face gold(porphyrin) moieties has been prepared and characterized. Absorption and luminescence spectroscopy, cyclic voltammetry, and EPR spectroscopy on [Au2(DPD)]n+ and a mononuclear reference are complemented by DFT and TDDFT calculations.

Mechanisms of separation of the elastic step and the thermal step

The elastic interaction causes a two‐step conversion from the low‐spin (LS) to the high‐spin state (HS) following a femtosecond laser pulse excitation. These steps occur on different timescales: a spin conversion (elastic step) in a short time due to pressure propagation and a late spin conversion (thermal step) resulting from heat diffusion. In this paper, we provide a brief review of models for spin crossover phenomena, emphasizing the role of the difference of degeneracy of the HS state and LS state and elastic interaction due to changes in local structures. We also review theoretical approaches to these effects. Additionally, to analyze the dynamical process of spin conversion after photo‐irradiation, it is necessary to consider mechanisms of heat transfer among spins. Recently, we proposed a two‐temperature model that incorporates both lattice and spin temperatures, which enables us to reproduce the two steps under an early uniformization of the lattice temperature, highlighting the importance of the timescales of these processes. Furthermore, we explore possible mechanisms to separate the two steps by examining the different timescales of processes of spin conversions by mechanical and entropic forces, and also by considering changes of local temperature due to spin conversion.

Silk Fibroin/Poly(1,4-Butylene Succinate) Composite with Improved Thermostability and Cytocompatibility

This paper describes our research on a facile and effective approach to fabricate novel silk fibroin/poly(1,4-butylene succinate) (SF/PBS) composites for the first time. Scanning electron microscopy (SEM), infrared spectra (IR), X-ray diffraction (XRD) and Thermogravimetric analysis (TGA) were used to investigate the morphology, chemical structure, crystalline state, thermostability and possible interactions of SF with PBS for the SF/PBS composites. In addition, the determinations of the EC109 cell viability was also been completed to explore the influence of SF/PBS mass ratio on cytocompatibility. Because of the composite of SF with the PBS, the thermostability and cell viability of the SF/PBS composites were higher than those of neat SF material. However, SF did not chemically react with PMMA during the formation of the composite, and SF hardly interacts with PBS in the composite.

Supramolecular Interactions as Key in Racemic Resolution: New Insights into the (SSi)‐ and (RSi)‐Diastereomers of (1R,2S,5R)‐Methyl(1‐naphthyl)‐phenylmenthoxysilane of Sommer

AbstractA highly selective approach with high yields of two diastereomeric silicon‐stereogenic menthoxysilanes, (RSi)‐3 and (SSi)‐3, introduced by Sommer et al., could be established as well as investigated in detail using different analytical tools. Single‐crystal X‐ray diffraction analysis was used to examine the different crystallization rates while Hirshfeld surface analysis was applied to extend supramolecular interactions in the solid state which showed stronger hydrogen bridges for the faster crystallizing diastereomer (SSi)‐3. In addition, similar ground‐state energies haven been found for both diastereomers by DFT calculations. Subsequent NMR studies showed stable Si‐configurations wherein epimerization only started after more than 4 hours at 110 °C. Access to both diastereomers with opposite configuration at the stereogenic silicon center is achievable in high yields and high stereochemical purity using only naturally occurring (−)‐menthol as a reagent.

First combined tuning on transverse kinematic imbalance data with and without pion production constraints

We present the first combined tuning, using , of four transverse kinematic imbalance measurements of neutrino-hydrocarbon scattering, both with and without pion final states, from the T2K and MINERvA experiments. As a proof of concept, we have simultaneously tuned the initial state and final-state interaction models (SF-CFG and hA, respectively), producing a new effective model that more accurately describes the data. Published by the American Physical Society 2024

The comprehensive large-scale redevelopment of Pazhou Village in Guangzhou, China: The interaction of state, market and local community

Urban villages are an important element of the urban environment in China. Often characterized by high densities, illegal construction and poor quality, the key issue of urban villages for city planners and officials is whether to try to comprehensively redevelop them or opt for gradual upgrading. This paper provides an evaluation of the comprehensive redevelopment of Pazhou Village in Guangzhou, China, after a decade and shows that under certain important conditions including good co-operation between governments, developers and village collectives, land use intensification and participatory planning, it is possible for comprehensive redevelopment to benefit the original villagers. The redevelopment was initiated by the local state and the case study examines the dynamic interactions between the key actors and their respective roles in ensuring the success of the development. Using the theory of state entrepreneurialism, the findings highlight the leading yet subtle role of the state in Chinese cities.

Unraveling the developmental heterogeneity within the human retina to reconstruct the continuity of retinal ganglion cell maturation and stage-specific intrinsic and extrinsic factors.

Tissue development is a complex spatiotemporal process with multiple interdependent components. Anatomical, histological, sequencing, and evolutional strategies can be used to profile and explain tissue development from different perspectives. The introduction of scRNAseq methods and the computational tools allows to deconvolute developmental heterogeneity and draw a decomposed uniform map. In this manuscript, we decomposed the development of a human retina with a focus on the retinal ganglion cells (RGC). To increase the temporal resolution of retinal cell classes maturation state we assumed the working hypothesis that that maturation of retinal ganglion cells is a continuous, non-discrete process. We have assembled the scRNAseq atlas of human fetal retina from fetal week 8 to week 27 and applied the computational methods to unravel maturation heterogeneity into a uniform maturation track. We align RGC transcriptomes in pseudotime to map RGC developmental fate trajectories against the broader timeline of retinal development. Through this analysis, we identified the continuous maturation track of RGC and described the cell-intrinsic (DEGs, maturation gene profiles, regulons, transcriptional motifs) and -extrinsic profiles (neurotrophic receptors across maturation, cell-cell interactions) of different RGC maturation states. We described the genes involved in the retina and RGC maturation, including de novo RGC maturation drivers. We demonstrate the application of the human fetal retina atlas as a reference tool, allowing automated annotation and universal embedding of scRNAseq data. Altogether, our findings deepen the current knowledge of the retina and RGC maturation by bringing in the maturation dimension for the cell class vs. state analysis. We show how the pseudotime application contributes to developmental-oriented analyses, allowing to order the cells by their maturation state. This approach not only improves the downstream computational analysis but also provides a true maturation track transcriptomics profile.

Tensor product space for studying the interaction of bipartite states of light with nanostructures

Tensor product space for studying the interaction of bipartite states of light with nanostructures

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species. The degree to which LC activity is homogenous across these factors, however, has never been assessed due to the small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) and show diversity across both intrinsic and extrinsic factors such as species, age, sex and brain state. We use a negative binomial regression model to compare activity from male monkeys, and rats and mice of both sexes that were recorded across brain states from brain slices ex vivo or under different anesthetics or during wakefulness in vivo . LC activity differed due to complex interactions of species, sex, and brain state. The LC became more active during aging, independent of sex. Finally, in contrast to the foundational principle that all species express two distinct LC firing modes ("tonic" or "phasic"), we discovered great diversity within spontaneous LC firing patterns. Different factors were associated with higher incidence of some firing modes. We conclude that the activity of the evolutionarily-ancient LC is not conserved. Inherent differences due to age and species-sex-brain state interactions have implications for understanding the role of LC in species-specific naturalistic behavior, as well as in psychiatric disorders, cardiovascular disease, immunology, and metabolic disorders.

Mice employ a bait-and-switch escape mechanism to de-escalate social conflict.

Intraspecies aggression has profound ecological and evolutionary consequences, as recipients can suffer injuries, decreases in fitness, and become outcasts from social groups. Although animals implement diverse strategies to avoid hostile confrontations, the extent to which social influences affect escape tactics is unclear. Here, we used computational and machine-learning approaches to analyze complex behavioral interactions as mixed-sex groups of mice, Mus musculus, freely interacted. Mice displayed a rich repertoire of behaviors marked by changes in behavioral state, aggressive encounters, and mixed-sex interactions. A distinctive behavioral sequence consistently occurred after aggressive encounters, where males in submissive states quickly approached and transiently interacted with females immediately before the aggressor engaged with the same female. The behavioral sequences were also associated with substantially fewer physical altercations. Furthermore, the male's behavioral state could be predicted by distinct features of the behavioral sequence, such as kinematics and the latency to and duration of male-female interactions. More broadly, our work revealed an ethologically relevant escape strategy influenced by the presence of females that may serve as a mechanism for de-escalating social conflict and preventing consequential reductions in fitness.

Unilateral acts of states in the international legal system

The article examines unilateral acts of states in the international legal system based on a complex systemic analysis. The methodological basis was the dialectical method, which made it possible to understand the essence of international legal obligations of states in inseparable unity and general connection. The relevance of the study is determined by the trends inherent in modern international law. First, with the development of information technologies, and especially with the development of forms of information transmission, the sphere of activity of states is transformed. An increasing number of interested persons knows their positions on a wide range of international legal issues. On the one hand, it simplifies the process of identifying the state’s position when its analysis is necessary for international legal qualification. On the other hand, in such a situation, the possibilities for interpreting the behavior of a specific state from the point of view of its agreement or disagreement with a certain legal situation expand. In the practice of international relations, there is an expansion of the system of sources of international law. The study of these sources is necessary for understanding the foundations of international law, solving specific international problems and increasing the effectiveness of international cooperation. As the practice of international jurisdictional bodies accumulated, the subject of study of which was unilateral acts of states, the research emphasis shifted from establishing the essence of unilateral acts to assessing their relationship with the sources of international law. It is noted that unilateral acts play an important independent role in the modern international system, which is characterized by both fragmentation and growing globalization. Modern means of communication have made it possible to make unilateral acts one of the most frequently used tools of state interaction. The appropriateness and necessity of the development of the legal regime of unilateral acts is emphasized and substantiated. Unilateral acts of states are recognized as independent additional sources of international law capable of generating international legal norms, and they can be found in the «sources» section of many leading international legal documents.

Pentadic Cartography and India’s Foreign Policy: Insights from Jaishankar’s GLOBSEC Forum Interview

ABSTRACT India’s rise as the world’s largest democracy and its challenge to the Western-defined global order have attracted significant scholarly, political, and media attention. Using Anderson and Prelli’s pentadic cartography to enhance discursive analysis in international relations, this paper looks at journalist Maithreyi Seetharaman’s interview with Subrahmanyam Jaishankar, India’s External Affairs Minister at the GLOBSEC Forum in Bratislava, Slovakia. Depicting three interlocking maps of the symbolic landscape of the interview, we highlight the use of Seetharaman and Jaishankar’s scene-act ratio, situating India’s actions in its geopolitical contexts. Jaishankar’s dual use of materialist and idealist discourses presents India as both a reactive agent influenced by external circumstances and a proactive agent with its own distinct goals and ethical considerations. This approach offers a comprehensive understanding of international politics, balancing dominant empirical narratives in IR and emphasising a complex interplay of motives that drive state behaviour. Through this case study, we advocate for a broader application of pentadic cartography in international relations to uncover the deeper meanings and contexts that shape state actions, providing a richer, more textured understanding of geopolitics, global diplomacy and state interaction.

The Solid-State Multi-Color Fluorescence Switching from a [2.2]Paracyclophane-Based Triarylborane.

The fluorophores, the fluorescence of which can be switched between multi bright colors in the solid state, show promising applications not only in the sophisticated multicolor display but also in the advanced encryption and anti-counterfeiting systems. However, it is very challenging to obtain such fluorophores. Herein, we disclose such an example, g-BPhANMe2-Cp, which contains an electron-donating dimethylamino (NMe2) and an electron-accepting [(2-dimesitylboryl)phenyl]acetyl at the pseudo-gem position of [2.2]paracyclophane skeleton. This molecule can display tricolor mechanochromic luminescence (MCL) due to the different responses of the mechanically ground amorphous state to heating and solvent-fuming. Owing to the absence of intermolecular π-π interactions in the solid state, the fluorescence efficiency is very high irrespective of its morphological state (ΦF=0.60-0.87). Moreover, this molecule also displays reversible acidochromic luminescence (ACL) by protonation and deprotonation of NMe2 with trifluoroacetic acid (TFA) and triethylamine (TEA), respectively. The protonated sample fluoresces (ΦF=0.31) at much shorter wavelength due to the interruption of intramolecular charge transfer process. Therefore, with the combination of tricolor MCL and ACL properties, the solid-state emission of g-BPhANMe2-Cp can be switched among four bright fluorescence colors of yellow, green, cyan and blue via treatment with appropriate stimulus.

Sublingual immune cell clusters and dendritic cell distribution in the oral cavity.

The oral mucosa is the first line of defense against pathogenic bacteria and plays a vital role in maintaining tolerance to food antigens and commensal bacteria. We used CD11c reporter mice to visualize dendritic cells (DCs), a key immune cell population, in the oral cavity. We identified differences in DC density in each oral tissue region. Sublingual immune cell clusters (SLICs) extended from the lamina propria to the epithelium, where DCs and T cells resided in close contact with each other and innate lymphoid cells (ILCs). Targeted in situ photolabeling revealed that the SLICs comprised mostly of CD11c+CD11b+ DCs and were enriched for cDC1s and Langerhans cells. Although the frequency of T cell subsets was similar within and outside the SLICs, tissue resident memory T cells were significantly enriched within the clusters and cluster size increased in response to inflammation. Collectively, we found that SLICs form a unique microenvironment that facilitates T cell-DC interactions in the steady state and during inflammation. Since the oral mucosa is an important target for needle-free vaccination and sublingual immunotherapy to induce tolerogenic responses, the novel insight into the localized immunoregulation provided in this study may accelerate the development of these approaches.

Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.

Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as invivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.

Benchmarking the non-flow contributions to the elliptic flow parameter (v 2) in proton-proton collisions

Abstract This manuscript reports on the elliptic flow parameter, $v_{_2}$, in proton-proton (p-p) collisions using PYTHIA8 event generator simulations. The typical Event Plane ($EP$) method $v_{_2}$($EP$) as the one used for the real data analysis has been adopted to measure the $v_{_2}$ of particles composed of different quark flavors, and produced at mid-pseudorapidity $|\eta| \le 1$ at center-of-mass energy $\sqrt{s}$ = 200 GeV and $\sqrt{s}$ = 13 TeV. The event plane has been constructed using the soft charged particles with transverse momentum ($p{_{_T}} < $ 2 GeV/c) produced in various $\eta$ ranges. The pseudorapidity gap technique ($\Delta\eta$) between the particle of interest and the soft charged particles contributed to the event plane constructions has been utilized to benchmark the non-flow contributions. The $v_{_2}^{\pi^{^\pm,}\pi^{^0}}$, $v_{_2}^{J/\psi,\Upsilon, K, D, B}$, and the $v_{_2}^{\gamma_{dir}}$ show similar pattern dependence on the transverse momentum for the same $\Delta\eta$, at both $\sqrt{s}$ = 200 GeV and $\sqrt{s}$ = 13 TeV. At each center-of-mass energy, the measured $v_{_2}$ shows obvious dependence on the quark flavor contents where $v_{_2}^{\gamma_{dir}}$ $\le$ $v_{_2}^{J/\psi, \Upsilon, K, D, B}$ $\le$ $v_{_2}^{\pi^{^\pm,}\pi^{^0}}$ for similar $\Delta\eta$ gap. The measured $v_{_2}$ shows slightly higher values at smaller $\sqrt{s}$ for particles of similar values of $\Delta\eta$ gaps, particularly at small $\Delta\eta$ gap. The measured $v_{_2}$ for all particles shows systematic decreases with increasing the $\Delta\eta$ gap as expected from the previous experimental results. Because PYTHIA8 simulations do not incorporate final state interactions, the $v_{_2}(EP)$ values reported here primarily reflect the non-flow contributions and its dependence on the quark contents, pseudorapidity gap as a function on $p_{T}$ at each center of mass-energy. These contributions should be carefully subtracted from the signal in real data analysis that employs the same event plane determination algorithm.

Superconductivity in ZrB12 under High Pressure

Transition metal borides have emerged as pivotal players in various fields. In addition to their exceptional properties such as high hardness, a high melting point, and corrosion resistance, certain compounds exhibit remarkable characteristics including superconductivity, magnetism, electrical conductivity, and catalytic activity. Among these compounds, ZrB12 has garnered significant attention due to its unique physicochemical properties. However, previous research on ZrB12 has predominantly focused on its mechanical behavior while overlooking the electron-electron interactions of the superconducting state. In this paper, resistance characterization of ZrB12 under high-pressure conditions was conducted to further investigate its superconductivity. Our research findings indicate that ZrB12 maintains its superconductivity within a pressure range of 0 to 1.5 GPa and is classified as a type 2 superconductor. Additionally, the results confirm the anisotropic nature of ZrB12’s superconductivity. As the pressure increases, the superconducting transition temperature undergoes a gradual decrease. Remarkably, ZrB12 exhibits metallic behavior under pressures up to 31.4 GPa. The observed decline in superconductivity in ZrB12 can be ascribed to the intensified influence of Zr’s movement on phonon dispersion, ultimately leading to a reduction in carrier concentration.

Towards Nickel-NHC Fluoro Complexes-Synthesis of Imidazolium Fluorides and Their Reactions with Nickelocene.

While hundreds of complexes of the general formula [Ni(η5-C5H5)(NHC)(X)] exist (NHC = a N-heterocyclic carbene, X = Cl, Br, I), none is yet known with X = F. We attempted to prepare such a species by reacting nickelocene with imidazolium fluorides. Three imidazolium fluorides (ImH)+ F- [Im = (N,N'-bis-(R)-imidazolium: 1a, IMe, R = Me; 1b, IMes, R = 2,4,6-trimethylphenyl; 1c, IPr, R = 2,6-diisopropylphenyl)] were prepared and characterized by spectroscopic methods. In addition, the salts 1b [(IMesH)+ F-] and 1c [(IPrH)+ F-] were subjected single-crystal X-ray diffraction experiments. The reactions of these imidazolium fluorides with nickelocene did not lead to [Ni(η5-C5H5)(NHC)(F)] species. Instead, the reaction of 1a [(IMeH)+ F-] and 1b [(IMesH)+ F-] with nickelocene led to the salt 2 [Ni(η5-C5H5)(IMe)2]+ F- and to the square planar complex 3atrans-[NiF2(IMes)2] respectively. Both complexes were characterized spectroscopically and by single crystal X-ray diffraction. All four X-ray diffraction studies reveal hydrogen bonding and hydrogen interactions with the F atom or anion, and in some cases with solvent molecules of crystallization, and these phenomena are all discussed. Complex 2, in particular, exhibited a wide range of interesting H-bonded interactions in the solid state. Complexes 2 and 3a were tested as catalysts for Suzuki-Miyaura coupling but were not promising: complex 2 was inactive, and while 3a did indeed catalyze the reaction, it gave widely diverging results owing to its instability in solution.