Sequential Mechanism Research Articles

Reading problems and their connection with visual search and attention.

Attention has been hypothesized to act as a sequential gating mechanism for the orderly processing of letters and words. These same visuoattentional processes are often assumed to partake in some but not all types of visual search. In the current study, 24 dyslexic and 36 typical readers completed an attentionally demanding visual conjunction search. Visual feature search served as an internal control. It has been suggested that reading problems should go hand in hand with specific problems in visual conjunction search-particularly elevated conjunction search slopes (time per search item)-often interpreted as a problem with visual attention. Results showed that reading problems were associated with slower visual search, especially conjunction search. However, reading deficits were not associated with increased conjunction search slopes but instead with increased search intercepts, traditionally not interpreted as reflecting attention. We discuss these results in the context of hypothesized visuoattentional problems in dyslexia. Remaining open to multiple interpretations of the data, the current study demonstrates that difficulties in visual search are associated with reading problems, in accordance with growing literature on visual cognition problems in developmental dyslexia.

A Deepening Political Crisis, Military Involvement and Economic Woes: Evidence From Pakistan

This paper discusses instances of growing military involvement, unceasing political crises and deepening economic grievances impacting Pakistan. The study contributes to the existing literature on three accounts: first, by taking Pakistan’s current context fuelled with regard to growing military engagement, strained civil–military relations and economic uncertainties, second, by explaining the relevance of the joint endogeneity principle with respect to political instability and economic growth and third, by theorizing the linkage of the political spectrum through existing hypotheses. It concludes that Pakistan needs to adopt sequential policy restructuring mechanisms and restore political stability to eliminate military involvement from its political fabric.

An alpha-helical lid guides the target DNA toward catalysis in CRISPR-Cas12a

CRISPR-Cas12a is a powerful RNA-guided genome-editing system that generates double-strand DNA breaks using its single RuvC nuclease domain by a sequential mechanism in which initial cleavage of the non-target strand is followed by target strand cleavage. How the spatially distant DNA target strand traverses toward the RuvC catalytic core is presently not understood. Here, continuous tens of microsecond-long molecular dynamics and free-energy simulations reveal that an α-helical lid, located within the RuvC domain, plays a pivotal role in the traversal of the DNA target strand by anchoring the crRNA:target strand duplex and guiding the target strand toward the RuvC core, as also corroborated by DNA cleavage experiments. In this mechanism, the REC2 domain pushes the crRNA:target strand duplex toward the core of the enzyme, while the Nuc domain aids the bending and accommodation of the target strand within the RuvC core by bending inward. Understanding of this critical process underlying Cas12a activity will enrich fundamental knowledge and facilitate further engineering strategies for genome editing.

Structural determination and kinetic analysis of the transketolase from Vibrio vulnificus reveal unexpected cooperative behavior.

Vibrio vulnificus (vv) is a multidrug-resistant human bacterial pathogen whose prevalence is expected to increase over the years. Transketolases (TK), transferases catalyzing two reactions of the nonoxidative branch of the pentose-phosphate pathway and therefore linked to several crucial metabolic pathways, are potential targets for new drugs against this pathogen. Here, the vvTK is crystallized and its structure is solved at 2.1 Å. A crown of 6 histidyl residues is observed in the active site and expected to participate in the thiamine pyrophosphate (cofactor) activation. Docking of fructose-6-phosphate and ferricyanide used in the activity assay, suggests that both substrates can bind vvTK simultaneously. This is confirmed by steady-state kinetics showing a sequential mechanism, on the contrary to the natural transferase reaction which follows a substituted mechanism. Inhibition by the I38-49 inhibitor (2-(4-ethoxyphenyl)-1-(pyrimidin-2-yl)-1H-pyrrolo[2,3-b]pyridine) reveals for the first time a cooperative behavior of a TK and docking experiments suggest a previously undescribed binding site at the interface between the pyrophosphate and pyridinium domains.

Common Sequential Organization of Face Processing in the Human Brain and Convolutional Neural Networks

Face processing includes two crucial processing levels – face detection and face recognition. However, it remains unclear how human brains organize the two processing levels sequentially. While some studies found that faces are recognized as fast as they are detected, others have reported that faces are detected first, followed by recognition. We discriminated the two processing levels on a fine time scale by combining human intracranial EEG (two females, three males, and three subjects without reported sex information) and representation similarity analysis. Our results demonstrate that the human brain exhibits a “detection-first, recognition-later” pattern during face processing. In addition, we used convolutional neural networks to test the hypothesis that the sequential organization of the two face processing levels in the brain reflects computational optimization. Our findings showed that the networks trained on face recognition also exhibited the “detection-first, recognition-later” pattern. Moreover, this sequential organization mechanism developed gradually during the training of the networks and was observed only for correctly predicted images. These findings collectively support the computational account as to why the brain organizes them in this way.

Application of biomaterial-based three-dimensional bioprinting for organ-on-a-chip fabrication

An organ-on-a-chip is a microfluidic device that simulates the microenvironment of organs, facilitating the study of human physiology and disease mechanisms. Through the integration of tissue engineering and micromachining technologies, it effectively manages the cellular microenvironment and implements tissue-specific functions and physiological responses with high fidelity. Several factors must be appropriately considered in the fabrication of an organ-on-a-chip, including the choice of biomaterials to simulate the extracellular matrix (ECM), selection of cells constituting the target organ, incorporation of humanized design to realize the primary function and structure of the organ, and the use of appropriate biofabrication methods to build a tissue-specific environment. Notably, three-dimensional (3D) bioprinting has emerged as a promising method for biofabricating organ-on-a-chip. Three-dimensional bioprinting offers versatility in adapting to various biomaterials with different physical properties, allowing precise control of 3D cell arrays and facilitating cyclic movements of fluidic flow within microfluidic platforms. These capabilities enable the precise fabrication of organ-on-a-chip that reflects tissue-specific functions and microenvironments. Additionally, 3D-bioprinted organ-on-a-chip can serve as a disease-on-a-chip platform, achieved through the implementation of pathophysiological environments and integration with devices such as bioreactors. Their significance in pharmacology research lies in their exceptional resemblance to the 3D microenvironment structure of actual organs, which are conducive for the validation of sequential mechanism of drug action. This review describes recent examples of organ-on-a-chip applications for various organs and state-of-the-art 3D bioprinting techniques employed in organ-on-a-chip fabrication. The discussion extends to the future prospects of this technology, encompassing aspects such as commercialization through mass production and its potential application in personalized medicine or drug-screening platforms. Serving as a relevant guide, this review offers insights for future research and developments in in vitro micromodel fabrication.

Kinetic analysis of the three-substrate reaction mechanism of an NRPS-independent siderophore (NIS) synthetase.

The biosynthesis of many bacterial siderophores employs a member of a family of ligases that have been defined as NRPS-independent siderophore (NIS) synthetases. These NIS synthetases use a molecule of ATP to produce an amide linkage between a carboxylate and an amine. Commonly used carboxylate substrates include citrate or α-ketoglutarate, or derivatives thereof, while the amines are often hydroxamate derivatives of lysine or ornithine, or their decarboxylated forms cadaverine and putrescine. Enzymes that employ three substrates to catalyze a reaction may proceed through alternate mechanisms. Some enzymes use sequential mechanisms in which all three substrates bind prior to any chemical steps. In such mechanisms, substrates can bind in a random, ordered, or mixed fashion. Alternately, other enzymes employ a ping-pong mechanism in which a chemical step occurs prior to the binding of all three substrates. Here we describe an enzyme assay that will distinguish among these different mechanisms for the NIS synthetase, using IucA, an enzyme involved in the production of aerobactin, as the model system.

Beyond 1 Million Nodes—Crowdsourced Video CDN: Architecture, Technology, and Economy

The video service has already become one of the Internet killer applications. To deliver the ever growing video traffic with the Quality of Experience (QoE) guarantee, deploying the infrastructure of Content Delivery Network (CDN) closer and closer to users has been a noticeable trend. And this trend becomes more promising when recently CDNs providers start utilizing the storage and network resources of the edge network devices (e.g., the Wi-Fi Access Points) for content delivery [13], i.e., crowdsourced CDN. In this article, we envision the crowdsourced CDN and propose a set of practical strategies to guide the implementation of such new paradigm. Firstly, we perform a large-scale measurement to explore the geo-content popularity and the geo-heterogeneity of the resource distribution. Benefiting from the measurement observations, we design the key solutions for the system operation, including regional content popularity prediction based on Markov Decision Process (MDP), region partition for the edge device organization and the collaborative content replication. Moreover, we consider the economic issues and propose a sequential auction mechanism to cope with the resource allocation when multiple Content Providers (CPs) compete for the edge resources for their content caching. We also demonstrate the performance gain of our design with data-driven simulation.

The adaptive flexibility of rhythmic attentional sampling in attending to multiple targets.

Recent behavioral and neural imaging studies revealed a rhythmic sampling in the theta-band (3-8 Hz) of attention. Such observation indicates that visual attention sequentially visits attended locations rapidly and periodically to cover multiple spatial locations, which is believed driven by a general sampling mechanism with a sampling rate invariant to the number of targets. However, a general sampling mechanism with a fixed rate would lead to the consequence that it would take longer time for attention to revisit the same item when attention needs to cover more items, which could impair perceptual continuity. It is unclear whether and how the attentional sampling mechanism can flexibly adapt to varying task demand to balance between covering more items and maintaining stable perception. Here with five behavioral experiments, we investigated how the sequential sampling mechanism adapts to the need of attending to from one to four locations. With state-of-the-art analysis methods, results show clear evidence of sequential sampling in attending to multiple locations, that both theta-band oscillations and phase-shift among different locations were observed in the behavioral performance. At each location, the oscillation period increased when the attended locations increased from one to three, maintaining a relatively stable attention-dwelling time at each location. Critically, oscillation period remained essentially the same from three to four, suggesting a flexible task-driven acceleration of attentional sampling to keep the revisiting duration within a reasonable range. Thus, our results reveal that the generally stable rhythmic attention mechanism could flexibly adjust its sampling rate to accommodate increased attentional demands. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

ОБОСНОВАНИЕ ПАРАМЕТРОВ ПОГРУЗОЧНО-ТРАНСПОРТНОГО АГРЕГАТА С РАСШИРЕННЫМИ ФУНКЦИОНАЛЬНЫМИ ВОЗМОЖНОСТЯМИ

The design of a loading and transport unit based on a stacker is proposed and developed, the service area is increased in relation to the base machine due to the use of a sequential structure manipulation mechanism, which reduces the time of performing a technological operation in automated production during loading, unloading and transportation of piece cylindrical cargoes in warehouse operations. A kinematic study of the loader mechanism has been carried out. A theoretical service area has been built. Stability in the longitudinal and transverse planes is calculated, the maximum weight of the lifted load and the angle of inclination at which the loader will lose stability are calculated.

M2-YOLOX: A Novel Method for Object Detection Based on an Improved YOLOX Algorithm Introducing a Global Attention Mechanism and a Feature Enhancement Module

Deep learning-based algorithms for detecting objects in remote sensing images have produced excellent results recently. However, the target recognition and classification process of remote sensing images has problems such as dense targets, uneven distribution, large-scale changes and complex backgrounds. In order to improve the effectiveness of existing detection methods, based on the YOLOX algorithm, a remote sensing image object detection algorithm introducing Global Attention Mechanism (GAM) and Feature Enhancement Module (FEM) proposed, named the M2-YOLOX(GAM+FEM+YOLOX) algorithm. First, a novel GAM module is developed that employs a sequential channel-space attention mechanism and redesigns the Convolutional Block Attention Module (CBAM), to address the issues of low effective information extraction and weak information representation of the feature map in the backbone network. CBAM is capable of amplifying global dimensional interaction features while reducing information dispersion as well. Second, the goal of the FEM is to improve the target feature extraction capabilities of the backbone feature extraction network by fusing numerous perceptual field features in lower-level feature maps. Then, the Flexible Rectified Linear Unit (FReLU) activation function is introduced under the action of feature fusion and global attention mechanism. Four-way feature map output in Feature Pyramid Networks (FPN) with Non-Maximum Suppression (NMS) and score filtering for object detection and output results. In comparison to the YOLOX algorithm, the experimental results show that the mAP value of the M2-YOLOX algorithm is improved by 0.0123, the LAMR value is decreased by 0.0150, the Precision rate value is increased by 0.105450, the Recall value is increased by 0.053250, and the mF1 value is increased by 0.0425.

Design, synthesis and preliminary biological evaluation of rivastigmine-INDY hybrids as multitarget ligands against Alzheimer's disease by targeting butyrylcholinesterase and DYRK1A/CLK1 kinases.

Based on a multitarget approach implementing rivastigmine-INDY hybrids 1, we identified a set of pseudo-irreversible carbamate-type inhibitors of eqBuChE that, after carbamate transfer at the active site serine residue, released the corresponding INDY analogues 2 endowed with hDYRK1A/hCLK1 kinases inhibitory properties. A SAR study and molecular docking investigation of both series of compounds 1 and 2 revealed that appropriate structural modifications at the carbamate moiety and at the N-appendage of the benzothiazole core led to potent and selective eqBuChE inhibitors with IC50 up to 27 nM and potent hDYRK1A and hCLK1 inhibitors with IC50 up to 106 nM and 17 nM respectively. Pleasingly, identification of the matched pair of compounds 1b/2b with a good balance between inhibition of eqBuChE and hDYRK1A/hCLK1 kinases (IC50 = 68 nM and IC50 = 529/54 nM, respectively) further validated our multitarget approach based on a sequential mechanism of action. In addition, target compound 1b exhibited a suitable ADMET profile, including good brain permeability and high stability in PBS, encouraging further biological investigation as a drug candidate.

Re-evaluation of the sequential 3α reaction in stellar conditions

The formation of carbon via the triple alpha process is a key step in stellar production reactions of light ions and heavily impacts the life-cycle of red giant stars. Here, we propose a novel theoretical approach for sequential mechanism of the helium burning process, based on the Imaginary Time Method (ITM) and semiclassical models. We compare our results to those of the NACRE collaboration, which has set the standard for the past decades. Our calculations differ by several orders of magnitude in the low temperature region, which may seriously affect the early evolution of helium burning stars.

Surface Engineering of Natural Killer Cells with CD44-targeting Ligands for Augmented Cancer Immunotherapy.

Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.

Physical modeling of the effect of refilling the melt into an ingot knock-off head on solidification and structure formation

The paper presents the results of a laboratory study of the effect of refilling the ingot knock-off head with melt in a certain time interval after pouring the ingot body on solidification and structure formation of the model ingot. The research was carried out by the method of physical (cold) modeling for which a laboratory installation (casting form-mold) was developed and manufactured. It allows visually studying the processes occurring during solidification and structure formation on a 19.6-ton model ingot. We used sodium sulfuric acid (crystalline hyposulfite) as a modeling solution. Correspondence of the processes occurring on the model and in real conditions of industrial ingots casting was evaluated using similarity criteria obtained on the basis of dimension theory with analysis of physico-chemical processes occurring during casting and crystallization of the ingot. Casting of the melt into the casting form-mold was downhill. In order to assess changes in the temperature field during casting and crystallization of the ingot in the entire solidification time, we performed thermometry of the mold model surface. Analysis of the conducted studies results showed that refilling the melt before 40 min leads to stimulation of early settling of crystals (“rain of crystals”), which contributes to an increase in the crystallization directivity in vertical direction. It was established that in a conventional ingot up to 40 min solidification proceeds by a sequential mechanism, and after that the crystals begin to settle (“rain of crystals”) and the solidification of the ingot passes through a volume-sequential mechanism. Refilling the ingot knock-off head with melt 40 min after pouring the ingot body contributed to the continuation of the sequential mechanism of ingot solidification, which led to the formation of a monolithic defect-free structure in the ingot body and the least development of shrinkage shell in the knock-off head. The results obtained make it possible to develop a technology for differentiated ingots casting when filling their knock-off heads with melt in a certain time interval after pouring the ingot body, which will affect the process of metal structure formation and reduce defective zones.

Role of the Solvent and Intramolecular Hydrogen Bonds in the Antioxidative Mechanism of Prenylisoflavone from Leaves of Vatairea guianensis.

This work discusses the electron structure, antioxidative properties, and solvent contribution of two new antioxidant molecules discovered, named S10 and S11, extracted from a medicinal plant called Vatairea guianensis, found in the Amazon rain-forest. To gain a better understanding, a study using density functional theory coupled with the polarizable-continuum model and the standard 6-311++G(d,p) basis set was conducted. The results indicate that S10 has a higher antioxidant potential than S11, confirming the experimental expectations. In the gas phase, the hydrogen atom transfer route dominates the hydrogen scavenging procedure. However, in the water solvents, the antioxidant mechanism prefers the sequential proton loss electron transfer mechanism. Furthermore, the solvent plays a fundamental role in the antioxidant mechanism. The formation of an intramolecular OH···OCH3 hydrogen bond is crucial for accurately describing the hydrogen scavenging phenomenon, better aligning with the experimental data. The results suggest that the two isoflavones investigated are promising for the pharmacologic and food industries.

COMPARATIVE ANALYSIS OF THE BEARING CAPACITY OF PLANETARY MECHANISMS FORMED ON THE BASIS BY TWO SIMPLE JAMES PLANETARY MECHANISMS, ACCORDING TO SEQUENTIAL NON-LOOP AND CLOSED KINEMATIC SCHEMES WITH ONE LOOP

The article presents a method for comparative analysis of the bearing capacity of planetary mechanisms of various kinematic schemes using several CAD/CAE software environments. To implement the method of comparative analysis, the KOMPAS-3D and SolidWorks software environments were used. In the first environment, calculations were performed according to the method of the GOST 21354-87 standard. The initial data and results of calculations performed by the KOMPAS-GEARS software package are stored in the appropriate files. In the second environment, a parametric 3D geometric solid model of the kinematic scheme of the planetary mechanism was created. According to this model, such characteristics of gears as mass and axial moment of inertia were determined. These characteristics are used to perform optimization calculations of the mass and speed of the designed planetary mechanism. The study of the speed of the planetary mechanism can be carried out in SolidWorks Motion. The overall dimensions of the model allow the designer to assess the acceptability of the design constraints for given dimensions to the specified requirements. According to the method, a study was made of the suitability of gear designs that were designed for a closed planetary mechanism as gears of an open-loop sequential planetary mechanism. The closed planetary gear is formed by two simple James planetary gears. The circuities planetary gear is formed by the series connection of the same simple planetary gears. Two cases of loading gears for a given kinematic scheme of the planetary mechanism were studied. Keywords: simple James planetary mechanism (mechanisms type ); closed planetary mechanism; contourless planetary gear; moment of inertia of gear-wheel; gear mass; planetary gear mass; contact strength of the gearing; bending strength of the gearing; toothing resource; 3D geometric solid model of the kinematic scheme of the planetary mechanism

A DFT study of the isomer variety of dimer-core argento-carbon clusters: From “butterflies” to side-attached to core–shell systems

Mixed metal-based nanosystems play increasingly important roles in modern technologies, and combination of silver and carbon have various current applications. Present DFT-based study addresses small carbon-silver clusters with minimal dicarbon component and predicts a few groups of flat and 3D isomers. They are analyzed and compared in terms of structure and stability, charge distribution and polarity, vibrations, and IR spectra. Structures with the C2 dopant at the periphery or centre of the Agn (n = 4–18) hosts are considered, found to exhibit considerable stabilities, and their evolution with the systems size is followed. Simulated IR spectra are predicted to be mainly represented by bands at low frequencies, characteristically dominated by a brightest line which can, however, split upon encapsulation of the carbon core inside the silver shell. Relative intensities of the spectra are related to the structural features, and a hypothetical sequential fragment-based exothermic mechanism for the core–shell system formation is considered.

Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives.

The selective functionalization of trifluoromethyl groups through C-F cleavage poses a significant challenge due to the high bond energy of the C(sp3)-F bonds. Herein, we present dihydroacridine derivatives as photocatalysts that can functionalize the C-F bond of trifluoromethyl groups with various alkenes under mild conditions. Mechanistic studies and DFT calculations revealed that upon irradiation, the dihydroacridine derivatives exhibit high reducibility and function as photocatalysts for reductive defluorination. This process involves a sequential single-electron transfer mechanism. This research provides valuable insights into the properties of dihydroacridine derivatives as photocatalysts, highlighting the importance of maintaining a planar conformation and a large conjugated system for optimal catalytic activity. These findings facilitate the efficient catalytic reduction of inert chemical bonds.

Modeling the Weak pH Dependence of Proton-Coupled Electron Transfer for Tryptophan Derivatives.

The oxidation of tryptophan (Trp) is an important step in many biological processes and often occurs by sequential or concerted proton-coupled electron transfer (PCET). The apparent rate constants for the photochemical oxidation of two Trp derivatives in water have been shown to be pH-independent at low pH and to exhibit weak pH dependence at higher pH. Herein, these systems are investigated with a general, multi-channel model that includes sequential and concerted mechanisms as well as various proton donors and acceptors. This model can reproduce the kinetic data for both Trp derivatives with physically meaningful parameters and suggests that the weak pH dependence may arise from the competition between OH- and H2O as proton acceptors in concerted PCET. Deprotonation of an ammonium group for one of the systems leads to a more complex pH dependence at higher pH. This work demonstrates the importance of considering multiple competing channels for the analysis of the pH dependence of apparent PCET rate constants.