Constriction Region Research Articles

Structural transformation between crystal and amorphous states and relating conductance variation in pure molybdenum nanocontacts

The amorphization and crystallization of the molybdenum (Mo) nanocontacts (NCs) via pulsed voltage application were observed in situ at the atomic resolution by transmission electron microscopy. Simultaneously, the variation in conductance of NCs during structural transformation was measured. The structural transformation could be controlled by the height of applied pulse waves. The amorphization was accelerated when NCs have longer constriction regions, which has not been found in NCs comprised of other metallic elements. The amorphized states of NCs were maintained during the observation at room temperature. The conductance ratio of amorphous Mo NCs to crystal Mo NCs was 0.62, which is lower than the ratio of liquid to solid Mo and is the lowest among those of other metallic NCs, leading to applications to advanced switching and memory functions.

Electric-Field-Driven Translocation of ssDNA through Hydrophobic Nanopores

The accurate sequencing of DNA using nanopores requires control over the speed of DNA translocation through the pores and also of the DNA conformation. Our studies show that ssDNA translocates through hourglass-shaped pores with hydrophobic constriction regions when an electric field is applied. The constriction provides a barrier to translocation and thereby slows down DNA movement through the pore compared with pores without the constriction. We show that ssDNA moves through these hydrophobic pores in an extended conformation and therefore does not form undesirable secondary structures that may affect the accuracy of partial current blockages for DNA sequencing.

Mapping of a novel clubroot resistance QTL using ddRAD-seq in Chinese cabbage (Brassica rapa L.)

BackgroundPlasmodiophora brassicae is a soil-borne plant pathogen that causes clubroot disease, which results in crop yield loss in cultivated Brassica species. Here, we investigated whether a quantitative trait locus (QTL) in B. rapa might confer resistance to a Korean P. brassicae pathotype isolate, Seosan. We crossed resistant and susceptible parental lines and analyzed the segregation pattern in a F2 population of 348 lines. We identified and mapped a novel clubroot resistance QTL using the same mapping population that included susceptible Chinese cabbage and resistant turnip lines. Forty-five resistant and 45 susceptible F2 lines along with their parental lines were used for double digest restriction site-associated DNA sequencing (ddRAD-seq). High resolution melting (HRM)-based validation of SNP positions was conducted to confirm the novel locus.ResultsA 3:1 ratio was observed for resistant: susceptible genotypes, which is in accordance with Mendelian segregation. ddRAD-seq identified a new locus, CRs, on chromosome A08 that was different from the clubroot resistance (CR) locus, Crr1. HRM analysis validated SNP positions and constricted CRs region. Four out of seventeen single nucleotide polymorphisms (SNPs) positions were within a 0.8-Mb region that included three NBS-LRR candidate genes but not Crr1.ConclusionThe newly identified CRs locus is a novel clubroot resistance locus, as the cultivar Akimeki bears the previously known Crr1 locus but remains susceptible to the Seosan isolate. These results could be exploited to develop molecular markers to detect Seosan-resistant genotypes and develop resistant Chinese cabbage cultivars.

Numerical Study of Creeping Flow Through Sinusoidally Periodic Tube

There has been renewed interest in the flow behaviour within tubes with periodically varying cross-section with the recognition that they can be used as particle separation devices. In this paper, we present a numerical study of the effect of tube geometry on creeping flow of viscous incompressible fluid through sinusoidally constricted periodic tube which is axisymmetric but longitudinally asymmetric. The boundary element method is used to solve for the flow in the tube by specifying the pressure drop across the ends of the tube. The boundary element equations have been formulated for ­an infinite periodic tube by writing the velocity in terms of the integrals over the tube boundary and is used to calculate the force on the tube boundary, to obtain the detailed velocity distribution within the tube and to determine the effect of amplitude and wavelength of corrugation on the structure of the flow. We have found that the highest axial velocity is at throat region and lowest axial velocity is at expansion region. Also, we have discovered that the maximum radial velocity occurs at diverging cross-section and minimum radial velocity occurs at converging cross-section. The tangential force on the tube wall is examined for different amplitudes and wavelengths of corrugation and observed that the tangential force is greater in the constricted region than in the expansion region. The physical quantities (such as velocity and force) increase with increasing amplitude and decrease with increasing wavelength. Finally, we have compared our results with the work of Hemmat and Borhan [3] and have found good agreement with them.

Electrostatic Probe Differential Analysis for Temperature Distribution Diagnostics of Constricted Arc Current-carrying Region in Sheet Slanting Tungsten Electrode with Insulating Solid Wall

Electrostatic Probe Differential Analysis for Temperature Distribution Diagnostics of Constricted Arc Current-carrying Region in Sheet Slanting Tungsten Electrode with Insulating Solid Wall

Fosfomycin Permeation through the Outer Membrane Porin OmpF

Fosfomycin is a frequently prescribed drug in the treatment of acute urinary tract infections. It enters the bacterial cytoplasm and inhibits the biosynthesis of peptidoglycans by targeting the MurA enzyme. Despite extensive pharmacological studies and clinical use, the permeability of fosfomycin across the bacterial outer membrane is largely unexplored. Here, we investigate the fosfomycin permeability across the outer membrane of Gram-negative bacteria by electrophysiology experiments as well as by all-atom molecular dynamics simulations including free-energy and applied-field techniques. Notably, in an electrophysiological zero-current assay as well as in the molecular simulations, we found that fosfomycin can rapidly permeate the abundant Escherichia coli porin OmpF. Furthermore, two triple mutants in the constriction region of the porin have been investigated. The permeation rates through these mutants are slightly lower than that of the wild type but fosfomycin can still permeate. Altogether, this work unravels molecular details of fosfomycin permeation through the outer membrane porin OmpF of E. coli and moreover provides hints for understanding the translocation of phosphonic acid antibiotics through other outer membrane pores.

Morphological Evaluation of the Nasopalatine Canal in Patients With Different Facial Profiles and Ages

To evaluate the influence of facial profile and age on the morphology of the nasopalatine canal. One hundred thirty-two cone-beam computed tomograms were classified according to facial profile-mesofacial, brachyfacial, and dolichofacial-and divided into the following age groups: 21 to 30, 31 to 40, 41 to 50, and 51 to 60years. Measurements were obtained for openings of the incisive and nasopalatine foramina, alveolar bone thickness, and the full length, most constricted region, and volume of the nasopalatine canal. Intra- and inter-examiner agreements were calculated using the intraclass correlation coefficient. After exploratory and descriptive analysis, data were subjected to 2-way analysis of variance and Tukey test for comparisons between facial profiles and age groups. The significance level was 5% (α=0.05). Intra- and inter-examiner reproducibilities were excellent for all measurements. Patients older than 50years presented a significantly larger nasopalatine canal than patients 21 to 30years old for all facial profiles (P≤.05). Linear measurements obtained from the nasopalatine canal showed no significant difference between facial profiles and age groups (P>.05). The nasopalatine canal was not influenced by facial profile but did exhibit an increased volume with aging, particularly after 50years of age.

Computational fluid dynamics analysis of H-uvulopalatopharyngoplasty in obstructive sleep apnea syndrome.

To explore the impact of H-uvulopalatopharyngoplasty (H-UPPP) in obstructive sleep apnea syndrome (OSAS) and gain insights into the potential mechanism underlying improvement by H-UPPP. In a cohort of 11 OSAS patients, computational fluid dynamics (CFD) models of the upper airway were obtained using commercial software from computed tomography (CT) datasets before and after H-UPPP. Morphological and numerical parameters were respectively computed and compared during the peak tidal inspiratory flow. The correlations among polysomnography endpoints, airway dimensions, and pre- and post-operative airflow properties were analyzed with Spearman's rank correlation. The preoperative minimum cross-sectional area was significantly increased by 89.56% (p < .05), with a positive correlation to the apnea hypoapnea index (AHI) (r = 0.974). However, the capacity of all pharyngeal regions was not significantly altered (p > .05). Following H-UPPP, we observed a significant increase in pressure and reduction of velocity (p < .05) in the previously constricted areas. The change in pressure and velocity were significantly correlated with AHI (r = 0.922 and r = 0.946, respectively). In addition, the pressure drop in the constricted area, oropharynx, and hypopharynx were also significantly decreased (p < .05). H-UPPP is capable of expanding the constricted region of the velopharynx and can decrease the airway resistance which will in turn decrease the workload necessary for breathing and facilitate inspiration.

First chromosome data on Steindachneridion doceanum (Siluriformes: Pimelodidae): a critically endangered catfish endemic of the Doce River basin, Brazil

ABSTRACT The present report represents the first cytogenetic description of Steindachneridion doceanum, great catfish which is currently at high extinction risk and it is listed as threatened on the red list of the Brazilian Ministry of the Environment, also are suggested karyotype relationships with other species of the same genus endemic from other river basins. The results revealed a diploid number of 2n = 56 and the karyotype composed of 18 metacentric, 20 submetacentric, 10 subtelocentric and 8 acrocentric chromosomes (NF = 104). The AgNORs and CMA3 signals were coincident in location occupying the short arm of an acrocentric chromosome pair (25th), in a secondary constriction. The 5S rDNA genes were localized on the short arms of one subtelocentric pair. C-banding revealed terminal blocks on the short arms on many chromosomes as well as terminal positive bands at the both ends of a submetacentric pair. C banding also revealed a large heterochromatic block in the secondary constriction (25th) region that was coincident with the AgNORs sites and CMA3+ bright bands. In spite S. doceanum represent an endemic taxon, in spite their geographic isolation their cytogenetic characteristics show similarities with other species of the genus.

Single-Molecule Dynamics and Discrimination between Hydrophilic and Hydrophobic Amino Acids in Peptides, through Controllable, Stepwise Translocation across Nanopores.

In this work, we demonstrate the proof-of-concept of real-time discrimination between patches of hydrophilic and hydrophobic monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when serine or isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent “molecular brake” on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

Getting Drugs through Small Pores: Exploiting the Porins Pathway in Pseudomonas aeruginosa.

Understanding molecular properties of outer membrane channels of Gram-negative bacteria is of fundamental significance as they are the entry point of polar antibiotics into bacteria. Outer membrane proteomics revealed OccK8 (OprE) to be among the five most expressed substrate specific channels of the clinically important Pseudomonas aeruginosa. The high-resolution X-ray structure and electrophysiology highlighted a very narrow pore. However, experimental in vitro methods showed the transport of natural amino acids and antibiotics, among them ceftazidime. We used molecular dynamics simulations to reveal the importance of the physicochemical properties of ceftazidime in modulating the translocation through OccK8, proposing a structure-function relationship. As in general porins, the internal electric field favors the translocation of polar molecules by gainful energy compensation in the central constriction region. Importantly, the comparatively narrow OccK8 pore can undergo a substrate-induced expansion to accommodate relatively large-sized substrates.

Electric-Field-Driven Translocation of ssDNA through Hydrophobic Nanopores.

The accurate sequencing of DNA using nanopores requires control over the speed of DNA translocation through the pores and also of the DNA conformation. Our studies show that ssDNA translocates through hourglass-shaped pores with hydrophobic constriction regions when an electric field is applied. The constriction provides a barrier to translocation and thereby slows down DNA movement through the pore compared with pores without the constriction. We show that ssDNA moves through these hydrophobic pores in an extended conformation and therefore does not form undesirable secondary structures that may affect the accuracy of partial current blockages for DNA sequencing.

The Over-Reset Phenomenon in Ta2O5 RRAM Device Investigated by the RTN-Based Defect Probing Technique

Despite the tremendous efforts in the past decade devoted to the development of filamentary resistive-switching devices (RRAM), there is still a lack of in-depth understanding of its over-reset phenomenon. At higher reset stop voltages that exceed a certain threshold, the resistance at high resistance state reduces, leading to an irrecoverable window reduction. The over-reset phenomenon limits the maximum resistance window that can be achieved by using a higher Vreset, which also degrades its potential in applications such as multi-level memory and neuromorphic synapses. In this letter, the over-reset is investigated by cyclic reset operations with incremental stop voltages, and is explained by defect generation in the filament constriction region of Ta2O5 RRAM devices. This is supported by the statistical spatial defects profile obtained from the random telegraph noise based defect probing technique. The impact of forming compliance current on the over-reset is also evaluated.

Second-Sphere Effects on Methane Hydroxylation in Cu-Zeolites

Two [Cu2O]2+ cores have been identified as the active sites of low temperature methane hydroxylation in the zeolite Cu-MOR. These cores have similar geometric and electronic structures, yet different reactivity with CH4: one reacts with a much lower activation enthalpy. In the present study, we couple experimental reactivity and spectroscopy studies to DFT calculations to arrive at structural models of the Cu-MOR active sites. We find that the more reactive core is located in a constricted region of the zeolite lattice. This leads to close van der Waals contact between the substrate and the zeolite lattice in the vicinity of the active site. The resulting enthalpy of substrate adsorption drives the subsequent H atom abstraction step-a manifestation of the "nest" effect seen in hydrocarbon cracking on acid zeolites. This defines a mechanism to tune the reactivity of metal active sites in microporous materials.

Molecular Structure and Permeability at the Interface between Phase-Separated Membrane Domains.

Phase-separated membrane domains, also known as lipid rafts, are believed to play an important role in cell function. Although most rafts are sterol-enriched membrane regions, evidence suggests that living cells may also contain gel-like rafts. Interactions between gel and fluid domains have a large impact on membrane properties, as is the case with permeability. The membrane permeability may reach a peak at the main phase transition temperature, by far exceeding the values recorded at the fluid phase. It has been proposed that gel-fluid interfaces are leaky, but the effect has not yet been demonstrated at the molecular level. Here, we performed atomistic molecular dynamics simulations of phospholipid bilayers with coexisting gel-like and fluid domains. We found that the thickness mismatch between both phases, the membrane elasticity, and the lipid packing acted together to promote the formation of a thickness minimum at the gel-fluid interface. Free energy calculations showed that pore-mediated ionic permeation was strongly facilitated at the constriction region, whereas water permeation by simple diffusion was only marginally affected. Long-lived, peristaltic undulations were recorded at the bulk fluid phase near the main transition temperature. They gave rise to thickness minima that, although shallower than the interface constrictions, could also enhance permeability. Finally, we demonstrated that an interface constriction was also formed at the boundaries of regular, cholesterol-enriched lipid rafts. Our simulation results will hopefully contribute to a better understanding of biological processes such as transport, signaling, and cellular damage promoted by low temperature and dehydration.

Flow of emulsion drops through a constricted microcapillary channel

Enhanced oil recovery methods based on emulsion injection in porous media are based on the higher pressure drop in the emulsion flow when it is compared to the flow of the continuous phase at the same flow rate. This phenomenon depends on both viscous and capillary effects at the pore scale as the drops flow through the pore throats. In this work, we present a broad numerical study on the flow of planar emulsion drops through a constricted microcapillary channel that represents a pore throat connecting two adjacent pore bodies in a typical porous media. The emulsion concentration in the constriction region was controlled by a process of continuous injection of drops upstream the narrow channel. Both velocity and traction fields at the channel boundaries and drop surface are computed with the Boundary Element Method, and the position of the free surfaces in the flow is evolved by solving a kinematic equation in a Lagrangian representation. We investigate the effects of drop size, drop-to-basis fluid viscosity ratio and capillary number on the pressure loss by using a mobility reduction factor. The flow rate – pressure drop relation is studied by analyzing the mobility reduction factor as a function of the capillary number. It was found that a more efficient pore scale mobility control by emulsion injection can be achieved for high-viscosity drops that have the same size or are larger than the constriction at very low capillary number.

Effect of conductance linearity and multi-level cell characteristics of TaOx-based synapse device on pattern recognition accuracy of neuromorphic system

To improve the classification accuracy of an image data set (CIFAR-10) by using analog input voltage, synapse devices with excellent conductance linearity (CL) and multi-level cell (MLC) characteristics are required. We analyze the CL and MLC characteristics of TaOx-based filamentary resistive random access memory (RRAM) to implement the synapse device in neural network hardware. Our findings show that the number of oxygen vacancies in the filament constriction region of the RRAM directly controls the CL and MLC characteristics. By adopting a Ta electrode (instead of Ti) and the hot-forming step, we could form a dense conductive filament. As a result, a wide range of conductance levels with CL is achieved and significantly improved image classification accuracy is confirmed.

Identification and Functional Analysis of the First Aquaporin from Striped Stem Borer, Chilo suppressalis.

Aquaporins are integral membrane proteins some of which form high capacity water-selective channels, promoting water permeation across cell membranes. In this study, we isolated the aquaporin transcript (CsDrip1) of Chilo suppressalis, one of the important rice pests. CsDrip1 included two variants, CsDrip1_v1 and CsDrip1_v2. Although CsDrip1_v2 sequence (>409 bp) was longer than CsDrip1_v1, they possessed the same open reading frame (ORF). Protein structure and topology of CsDrip1 was analyzed using a predicted model, and the results demonstrated the conserved properties of insect water-specific aquaporins, including 6 transmembrane domains, 2 NPA motifs, ar/R constriction region (Phe69, His194, Ser203, and Arg209) and the C-terminal peptide sequence ending in “SYDF.” Our data revealed that the Xenopus oocytes expressing CsDrip1 indicated CsDrip1 could transport water instead of glycerol, trehalose and urea. Further, the transcript of CsDrip1 expressed ubiquitously but differentially in different tissues or organs and developmental stages of C. suppressalis. CsDrip1 mRNA exhibited the highest level of expression within hindgut and the third instar larvae. Regardless of pupae and adults, there were significantly different expression levels of CsDrip1 gene between male and female. Different from at low temperature, the transcript of CsDrip1 in larvae exposed to high temperature was increased significantly. Moreover, the mRNA levels of CsDrip1 in the third instar larvae, the fifth instar larvae, pupae (male and female), and adults (male and female) under different humidities were investigated. However, the mRNA levels of CsDrip1 of only female and male adults were changed remarkably. In conclusions, CsDrip1 plays important roles in maintaining water homeostasis in this important rice pest.

Enrofloxacin Permeation Pathways across the Porin OmpC

In Gram-negative bacteria, the lack or quenching of antibiotic translocation across the outer membrane is one of the main factors for acquiring antibiotic resistance. An atomic-level comprehension of the key features governing the transport of drugs by outer-membrane protein channels would be very helpful in developing the next generation of antibiotics. In a previous study [ J. D. Prajapati et al. J. Chem. Theory Comput. 2017 , 13 , 4553 ], we characterized the diffusion pathway of a ciprofloxacin molecule through the outer membrane porin OmpC of Escherichia coli by combining metadynamics and a zero-temperature string method. Here, we evaluate the diffusion route through the OmpC porin for a similar fluoroquinolone, that is, the enrofloxacin molecule, using the previously developed protocol. As a result, it was found that the lowest-energy pathway was similar to that for ciprofloxacin; namely, a reorientation was required on the extracellular side with the carboxyl group ahead before enrofloxacin reached the constriction region. In turn, the free-energy basins for both antibiotics are located at similar positions in the space defined by selected reaction coordinates, and their affinity sites share a wide number of porin residues. However, there are some important deviations due to the chemical differences of these two drugs. On the one hand, a slower diffusion process is expected for enrofloxacin, as the permeation pathway exhibits higher overall energy barriers, mainly in the constriction region. On the other hand, enrofloxacin needs to replace some polar interactions in its affinity sites with nonpolar ones. This study demonstrates how minor chemical modifications can qualitatively affect the translocation mechanism of an antibiotic molecule.

A tunable microfluidic 3D stenosis model to study leukocyte-endothelial interactions in atherosclerosis.

Atherosclerosis, a chronic inflammatory disorder characterized by endothelial dysfunction and blood vessel narrowing, is the leading cause of cardiovascular diseases including heart attack and stroke. Herein, we present a novel tunable microfluidic atherosclerosis model to study vascular inflammation and leukocyte-endothelial interactions in 3D vessel stenosis. Flow and shear stress profiles were characterized in pneumatic-controlled stenosis conditions (0%, 50% and 80% constriction) using fluid simulation and experimental beads perfusion. Due to non-uniform fluid flow at the 3D stenosis, distinct monocyte (THP-1) adhesion patterns on inflamed [tumor necrosis factor-α (TNF-α) treated] endothelium were observed, and there was a differential endothelial expression of intercellular adhesion molecule-1 (ICAM-1) at the constriction region. Whole blood perfusion studies also showed increased leukocyte interactions (cell rolling and adherence) at the stenosis of healthy and inflamed endothelium, clearly highlighting the importance of vascular inflammation, flow disturbance, and vessel geometry in recapitulating atherogenic microenvironment. To demonstrate inflammatory risk assessment using leukocytes as functional biomarkers, we perfused whole blood samples into the developed microdevices (80% constriction) and observed significant dose-dependent effects of leukocyte adhesion in healthy and inflamed (TNF-α treated) blood samples. Taken together, the 3D stenosis chip facilitates quantitative study of hemodynamics and leukocyte-endothelial interactions, and can be further developed into a point-of-care blood profiling device for atherosclerosis and other vascular diseases.