Description Of Mechanisms Research Articles

Molecular mechanisms of lipid droplets-mitochondria coupling in obesity and metabolic syndrome: insights and pharmacological implications

Abnormal lipid accumulation is a fundamental contributor to obesity and metabolic disorders. Lipid droplets (LDs) and mitochondria (MT) serve as organelle chaperones in lipid metabolism and energy balance. LDs play a crucial role in lipid storage and mobilization, working in conjunction with MT to regulate lipid metabolism within the liver, brown adipose tissue, and skeletal muscle, thereby maintaining metabolic homeostasis. The novelty of our review is the comprehensive description of LD and MT interaction mechanisms. We also focus on the current drugs that target this metabolism, which provide novel approaches for obesity and related metabolism disorder treatment.

Integrating Enzyme-Based Kinetics in Reactive Transport Models to Simulate Spatiotemporal Dynamics of Biomarkers during Chlorinated Ethene Degradation.

Biomarkers such as functional gene mRNA (transcripts) and proteins (enzymes) provide direct proof of metabolic regulation during the reductive dechlorination (RD) of chlorinated ethenes (CEs). Yet, current models to simulate their spatiotemporal variability are not flexible enough to mimic the homologous behavior of RDase functional genes. To this end, we developed new enzyme-based kinetics to model the concentrations of CEs together with the transcript and enzyme levels during RD. First, the model was calibrated to existing microcosm data on RD of cis-DCE. The model mirrored the tceA and vcrA gene expression and the production of their enzymes in Dehalococcoides spp. Considering tceA and vcrA as homologous instead of nonhomologous improved fitting of the mRNA time series. Second, CEs and biomarker patterns were explored as a proof of concept under groundwater flow conditions, considering degraders occurring in immobile and mobile states. Under both microcosm and flow conditions, biomarker-rate relationships were nonlinear hysteretic because tceA and vcrA acted as homologous genes. The mobile biomarkers additionally undergo advective-dispersive transport, which increases the nonlinearity and makes the observed patterns even more challenging to interpret. The model offers a thorough mechanistic description of RD while also allowing simulation of spatiotemporal dynamic patterns of various key biomarkers in aquifers.

Elucidating the Signaling Pathways Involved in Erectile Dysfunction

Background: Erectile Dysfunction (ED) is a common sexual disorder among men aged 20 years and over. It is predominantly characterized by alterations in the key physiological pathways regulating erectile function, such as nitric oxide and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK). Beyond these pathways, multiple molecular signaling networks are involved in ED pathogenesis. Objective: This review aims todescribe the major signal transduction pathways that impact erectile function and contribute to the introduction of the pathogenesis of ED. Methods: A literature review of ED was performed from 2000 to 2023 using PubMed, Scopus, and Embase. “ED” and “related signaling pathway”, “molecular mechanisms” terms were used. Results: Further basic and clinical studies are required to define the underlying molecular mechanisms of ED. The signaling pathways that were not affected by phosphodiesterase type 5 inhibitors (PDE5i) may be the reason for the reduced efficacy of this first-line treatment option in a variety of conditions. Conclusion: There is still a need for a deeper description of the molecular mechanisms in terms of fibrosis, angiogenesis, apoptosis, inflammation, oxidative stress, autophagy, and hypoxia to identify new possible targets underlying the pathogenesis of ED. This comprehensive review expounds on the principal signaling pathways, offering valuable insights that may catalyze the development of innovative and enhanced therapies for managing ED.

Elucidating impacts of partitioning and transmembrane permeability on absorption of chemicals in human gastrointestinal tract

Estimating the fraction absorbed (Fabs) of orally ingested chemicals in the human gastrointestinal tract is pivotal for assessing chemical concentrations in the systemic circulation and informing potential toxicological impacts, especially in the era of “new approach methods” targeting chemical screening and prioritization. Here, we present an input-parsimonious and computationally efficient approach to support the screening-level estimation of Fabs from partitioning (characterized using the octanol–water partition coefficient at pH 7.4, KOW) and transmembrane permeability (characterized using the Caco-2 apparent permeability, Papp,Caco-2), based on a mechanistic description of processes involved in chemical absorption:Fabs=1-e-164571-2.40×10-9+2.40×10-9∙KOW∙10.0075∙1Papp,Caco-2-10.001530.346+10.00115Our approach demonstrates satisfactory performance in predicting Fabs for 176 hydrophobic and hydrophilic organic chemicals, with a Pearson correlation coefficient greater than 0.75 and a root mean square error of approximately 15 % in absolute Fabs values between experimental measurements and predictions. Our results show that the Fabs of highly hydrophobic chemicals (KOW > 108) are closely dependent on partitioning, whereas the Fabs of relatively hydrophilic chemicals (KOW < 106) are sensitive to transmembrane permeability. We also demonstrate that transmembrane permeability and partitioning are not interdependent, and both should be treated as fundamental chemical properties in predicting Fabs.

Do regular quantum black holes exist?

Regular black holes do not exist in any classical theory of gravity including Einstein's general relativity. This unappealing feature is due to the appearance of a singularity in the interior of the black hole described by any classical theory. As Hawking argued, all known laws of physics must break down at the singularity. It is thus an important question whether this singularity can disappear in a quantum mechanical description of spacetime. In this letter, we therefore quantize the black hole interior in a Kantowski-Sachs minisuperspace representation in the presence of spontaneous Klein-Gordon matter field fluctuations. This leads to a Wheeler-DeWitt equation whose solution yields the interior wave function of the black hole. The regular part of this wave function satisfies the DeWitt boundary condition in that it vanishes at the singularity. Moreover, the wave function is regular and well behaved in the region around the singularity. These features of the wave function suggest that regular black holes do exist in quantum gravity.

What Can CISS Teach Us about Electron Transfer?

Electron transfer (eT) processes have garnered the attention of chemists and physicists for more than seven decades, and it is commonly believed that the essential features of the electron transfer mechanism are well understood─despite some open questions relating to the efficiency of long-range eT in some systems and temperature effects that are difficult to reconcile with the existing theories. The chiral induced spin selectivity (CISS) effect, which has been studied experimentally since 1999, demonstrates that eT through chiral systems depends on the electron's spin. Attempts to explain the CISS effect by adding spin-orbit coupling to the existing eT theories fails to reproduce the experimental results quantitatively, and it has become evident that the theory for explaining CISS must consider electron-vibration and/or electron-electron interactions. In this Perspective we identify some features of the CISS effect that imply that we should reconsider and refine the Marcus-Levich-Jortner mechanistic description for eT processes, especially for nonlinear systems and in the case of long-range eT.

Towards a complete description of the reaction mechanisms between nitrenium ions and water.

Nitrenium ions are intermediates in the metabolic routes producing the highly carcinogenic nitrosamines and binding to DNA molecules. The reaction mechanism of nitrenium molecules with explicit water molecules is sensibly dependent on the number of waters: when a second molecule is involved, it acts as a catalyst for the reaction, lowering intrinsic activation barriers regardless of the substituent. For all cases, the reaction force constants and reaction electron flux indicate highly synchronous reactions for . Conversely, for highly non-synchronous reactions are obtained, involving two separate proton transfers happening early and late in the reaction path. As a test case, for the simplest reactions, orbital interactions within the NBO paradigm, bond orders, and their derivatives indicate that each individual proton transfer is highly synchronous. Molecular geometries were optimized and characterized at the B3LYP/6-311++G(d, p) level. Intrinsic reaction coordinates were calculated. CCSD(T) single point energies with the same basis were computed on all stationary points. The reaction force, reaction force constant, and reaction electron flux are used to study the evolution of the reacting systems. Natural bond orbitals are used to understand the primitive changes driving the reaction.

Fermi and Luttinger Arcs: Two Concepts, Realized on One Surface.

We present an analytically solvable model for correlated electrons, which is able to capture the major Fermi surface modifications occurring in both hole- and electron-doped cuprates as a function of doping. The proposed Hamiltonian qualitatively reproduces the results of numerically demanding many-body calculations, here obtained using the dynamical vertex approximation. Our analytical theory provides a transparent description of a precise mechanism, capable of driving the formation of disconnected segments along the Fermi surface (the highly debated "Fermi arcs"), as well as the opening of a pseudogap in hole and electron doping. This occurs through a specific mechanism: The electronic states on the Fermi arcs remain intact, while the Fermi surface part where the gap opens transforms into a Luttinger arc.

Topological dynamics of adiabatic cat states

We consider a quantum topological frequency converter, realized by coupling a qubit to two slow harmonic modes. The dynamics of such a system is the quantum analog of topological pumping. Our quantum mechanical description shows that an initial state generically evolves into a superposition of two adiabatic states. The topological nature of the coupling between the qubit and the modes splits these two components apart in energy: for each component, an energy transfer at a quantized rate occurs between the two quantum modes, in opposite directions for the two components, reminiscent of the topological pumping. We denote such a superposition of two quantum adiabatic states distinguishable through measures of the modes’ energy an adiabatic cat state. We show that the topological coupling enhances the entanglement between the qubit and the modes, and we unveil the role of the quantum or Fubini-Study metric in the characterization of this entanglement.

Gamification: characteristics, trends, risks

Digital technologies development stimulates game elements inclusion into culture and different spheres of society. The identification of regularities and specifics of this process became the purpose of the study. The research methodology was based on the J. Huizing’s “man playing” concept and K. Verbach’s system description of gamification mechanisms. On the basis of these concepts, a grid of typical features of gamification has been compiled and gamification processes in different sociospheres analyzed. The research methods included the emerging gamification practices analysis. Based on the analysis results, trends and risks of implementing the game element into culture have been identified. The complex influence of gamification process on society and culture is manifested by consumers’ demand for interactivity, personal participation, and involvement (immersiveness) in almost all types of activities. These needs are strengthened under the influence of clip culture, making it easier for individuals to assimilate disparate and fragmented pieces of information. The request for immersiveness is closely related to the human need to be the author of the “text”, to control the plot, to create a plurality of readings (hypertext). It has been shown that gamification stimulates innovation in various areas, leads to the emergence of new products, processes, and services. The main risks of gamification development have been highlighted: hyperorientation to entertainment in areas that traditionally involve effort, and manipulation of people’s behavior in areas related to “shoulds”.

Inferring geometrical dynamics of cell nucleus translocation

The ability of eukaryotic cells to squeeze through constrictions is limited by the stiffness of their large and rigid nucleus. However, migrating cells are often able to overcome this limitation and pass through constrictions much smaller than their nucleus, a mechanism that is not yet understood. Here, we propose a methodological framework to observe, quantify, and model this phenomenon through a data-driven approach using microfluidic devices where cells migrate through controlled narrow spaces of sizes comparable to the ones encountered in physiological situations. Stochastic force inference is applied to experimental nuclear trajectories and nuclear shape descriptors, resulting in equations that effectively describe the kinematics of this phenomenon. By employing a model where the channel geometry is an explicit parameter and by training it over experimental data with different sizes of constrictions, we ensure that the resulting equations are predictive. Altogether, the approach developed here paves the way for a mechanistic and quantitative description of dynamical cell complexity during its motility. Published by the American Physical Society 2024

Comments on wormholes and factorization

In AdS/CFT partition functions of decoupled copies of the CFT factorize. In bulk computations of such quantities contributions from spacetime wormholes which link separate asymptotic boundaries threaten to spoil this property, leading to a “factorization puzzle.” Certain simple models like JT gravity have wormholes, but bulk computations in them correspond to averages over an ensemble of boundary systems. These averages need not factorize. We can formulate a toy version of the factorization puzzle in such models by focusing on a specific member of the ensemble where partition functions will again factorize.As Coleman and Giddings-Strominger pointed out in the 1980s, fixed members of ensembles are described in the bulk by “α-states” in a many-universe Hilbert space. In this paper we analyze in detail the bulk mechanism for factorization in such α-states in the topological model introduced by Marolf and Maxfield (the “MM model”) and in JT gravity. In these models geometric calculations in α states are poorly controlled. We circumvent this complication by working in approximate α states where bulk calculations just involve the simplest topologies: disks and cylinders.One of our main results is an effective description of the factorization mechanism. In this effective description the many-universe contributions from the full α state are replaced by a small number of effective boundaries. Our motivation in constructing this effective description, and more generally in studying these simple ensemble models, is that the lessons learned might have wider applicability. In fact the effective description lines up with a recent discussion of the SYK model with fixed couplings [1]. We conclude with some discussion about the possible applicability of this effective model in more general contexts.

Rolled‐Up Membranes from GaAs/AlOx Core‐Shell Nanowire Ensembles Through Natural Oxidation

AbstractThe formation of rolled‐up cylindrical membranes stemming from the strain deformation‐induced delamination of a film‐like nanowires array composed of coalesced GaAs nanowires embedded in AlOx with a buried GaAs/AlAs core‐shell structure is reported. The delamination of the nanowires array film is driven by natural oxidation resulting from prolongated exposure to ambient atmosphere. Investigation of the structural characteristics of the nanowires in the array reveals an analytical description of the oxidation mechanism leading to the formation of the rolled‐up structures. The membrane can easily transfer by simply shaking off the surface membranes of the sample. The cylindrical membranes maintain the optical properties of the core GaAs nanowires surrounded by native oxide. The findings show the prospects for area‐saving and transferable semiconductor devices with advanced nanoscale optical functions.

Scalable quantum detector tomography by high-performance computing

Abstract At large scales, quantum systems may become advantageous over their classical counterparts at performing certain tasks. Developing tools to analyze these systems at the relevant scales, in a manner consistent with quantum mechanics, is therefore critical to benchmarking performance and characterizing their operation. While classical computational approaches cannot perform like-for-like computations of quantum systems beyond a certain scale, classical high-performance computing (HPC) may nevertheless be useful for precisely these characterization and certification tasks. By developing open-source customized algorithms using high-performance computing, we perform quantum tomography on a megascale quantum photonic detector covering a Hilbert space of 106. This requires finding 108 elements of the matrix corresponding to the positive operator valued measure (POVM), the quantum description of the detector, and is achieved in minutes of computation time. Moreover, by exploiting the structure of the problem, we achieve highly efficient parallel scaling, paving the way for quantum objects up to a system size of 1012 elements to be reconstructed using this method. In general, this shows that a consistent quantum mechanical description of quantum phenomena is applicable at everyday scales. More concretely, this enables the reconstruction of large-scale quantum sources, processes and detectors used in computation and sampling tasks, which may be necessary to prove their nonclassical character or quantum computational advantage.

Quantitative Study on Reinforcing Mechanism of Nanofiller Network in Silicone Elastomer Based on Fluorescence Labeling Technology

Although there have been many theoretical studies on the enhancement effect of nanofiller networks and their interaction with elastomer molecular chains on the mechanical properties of elastomers, its mechanism description is still not completely clear. One of the main obstacles is the lack of quantitative characterization techniques and corresponding theoretical models for the three-dimensional morphology of complex nanofiller networks. In this paper, the precipitated silica-filled silicone rubber was studied by fluorescence labeling combined with laser scanning confocal microscopy, and the real three-dimensional images of dispersion and aggregation structure of filled rubber systems were obtained. The microstructure evolution of nano-particle aggregates caused by the increase in the filler volume fraction was quantitatively described, and the reinforcement mechanism of elastomers with a distribution of aggregates and filler networks composed of nanoparticles was studied. Furthermore, a nano-composite reinforcement model based on volume fraction, particle shape, interaction, and filler dispersion has been proposed.

Using artificial neural networks to elucidate retention interactions on stationary phases with amine moieties dedicated to supercritical fluid chromatography

The retention mechanisms of small molecules on a wide range of stationary phases using different mobile phase compositions are one of the most discussed topics in current state-of-the-art supercritical fluid chromatography (SFC). Although various theories have been published on retention behavior, prediction, and stability over time, an in-depth insight into the mechanisms is still lacking. Our study focused on the description of the retention mechanisms on columns with amine moieties, i.e., 2-ethylpyridine, 2-picolylamine, 1-aminoanthracene, and diethylamine, dedicated to SFC, using three different compositions of organic modifier, i.e., methanol, methanol + 10 mmol/L NH3, and methanol + 2 % H2O, in CO2. An extensive set of analytes characterized by more than 200 molecular descriptors was used. The importance of the effect of each molecular descriptor on the retention behavior was determined by artificial neural networks. Thus, the descriptors increasing and/or decreasing retention on individual columns using different mobile phase compositions were defined. The data collected over one year of column use were statistically evaluated to describe the retention behavior of small molecules on the tested stationary phases using three organic modifiers and to describe the changes in retention behavior over time.As the development of the SFC method can be laborious and time-consuming, this publication offers a detailed description of the interactions taking place between the analyte and the SFC stationary phase. Understanding these fundamental processes will enable faster development of SFC methods using quality-by-design principles.

Physics-informed neural networks for dynamic process operations with limited physical knowledge and data

In chemical engineering, process data are expensive to acquire, and complex phenomena are difficult to fully model. We explore the use of physics-informed neural networks (PINNs) for modeling dynamic processes with incomplete mechanistic semi-explicit differential–algebraic equation systems and scarce process data. In particular, we focus on estimating states for which neither direct observational data nor constitutive equations are available. We propose an easy-to-apply heuristic to assess whether estimation of such states may be possible. As numerical examples, we consider a continuously stirred tank reactor and a liquid-liquid separator. We find that PINNs can infer immeasurable states with reasonable accuracy, even if respective constitutive equations are unknown. We thus show that PINNs are capable of modeling processes when relatively few experimental data and only partially known mechanistic descriptions are available, and conclude that they constitute a promising avenue that warrants further investigation.

Формализованные схемы механизма управления организационной системой, реализующей циклы производства как совокупность разнородных бизнес-процессов

The article is devoted to the development of a mechanism for the efficient use of available resources of the organiza-tional system (OS) of a manufacturing enterprise with a cascade model of the production life cycle, in the context of the need to promptly increase the volume of manufactured products and reduce the time of delivery of products to the customer. Object of study: mechanism of resource management of the OS. Subject of study: formal aspects of this mechanism that help reduce the risk of making irrational heuristic decisions. Purpose of study: development of a for-mal-ized description of an effective mechanism of resource management of the OS. Methods: resource and process approach to management, project management and analogy method, methods and means of schematic modeling of electronic means. Main results and their significance: for individual business processes and the entire production cycle, based on the introduced components, formalized diagrams of the mechanism of optimal resource management of the OS were constructed, which made it possible, based on their application, to increase the efficiency of using the availa-ble re-sources of the enterprise and increase the output (rate of production) of its final products. Limitations of the de-veloped approach are shown.

World Trends in State Regulation of the Development of Organic Agriculture and the Market of Organic Products: The Experience of the USA, the EU and Russia

The relevance of the topic of research is determined by the need to address the problems of environmental and socioeconomic nature arising against the background of industrialized society, which causes interest in the development of organic agriculture and the formation of a dynamically growing market for organic products. The purpose of the study is to analyze the trends in the development of the global organic market and a comparative analysis of the practices of state regulation of this segment in the United States, the EU and Russia. In the course of the work such scientific methods as synthesis and deduction were used; the information and analytical base was the data of the journal “The World of Organic Agriculture” and publicly available information from the official websites of the Ministries of Agriculture of the United States and the Russian Federation, the European Commission, the Union of Organic Agriculture. The article presents the results of consideration of the dynamics of sales volumes and changes in the average per capita consumption of organic products in the world market, as well as the description of mechanisms of state regulation of organic agriculture and the organic market in the United States, the EU and Russia, highlighting their distinctive characteristics. The study of such issues allows to rationally apply foreign experience, excluding a high degree of risk when making strategic decisions in the formation of directions of development of the agrarian sector of the economy within the framework of national interests. The results of the study can be useful both in the development of programs for the development of organic agriculture at the level of sub-sectors of the economy, and in relation to the subjects of the Russian Federation, striving for sustainable development of the regional market of this type of products.

Axion detection via superfluid 3He ferromagnetic phase and quantum measurement techniques

We propose to use the nuclear spin excitation in the ferromagnetic A1 phase of the superfluid 3He for the axion dark matter detection. This approach is striking in that it is sensitive to the axion-nucleon coupling, one of the most important features of the QCD axion introduced to solve the strong CP problem. We review a quantum mechanical description of the nuclear spin excitation and apply it to the estimation of the axion-induced spin excitation rate. We also describe a possible detection method of the spin excitation in detail and show that the combination of the squeezing of the final state with the Josephson parametric amplifier and the homodyne measurement can enhance the sensitivity. It turns out that this approach gives good sensitivity to the axion dark matter with the mass of O\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\mathcal{O} $$\\end{document}(1) μeV depending on the size of the external magnetic field. We estimate the parameters of experimental setups, e.g., the detector volume and the amplitude of squeezing, required to reach the QCD axion parameter space.