Junction Gaps Research Articles

Mattertronics for programmable manipulation and multiplex storage of pseudo-diamagnetic holes and label-free cells

Manipulating and separating single label-free cells without biomarker conjugation have attracted significant interest in the field of single-cell research, but digital circuitry control and multiplexed individual storage of single label-free cells remain a challenge. Herein, by analogy with the electrical circuitry elements and electronical holes, we develop a pseudo-diamagnetophoresis (PsD) mattertronic approach in the presence of biocompatible ferrofluids for programmable manipulation and local storage of single PsD holes and label-free cells. The PsD holes conduct along linear negative micro-magnetic patterns. Further, eclipse diode patterns similar to the electrical diode can implement directional and selective switching of different PsD holes and label-free cells based on the diode geometry. Different eclipse heights and junction gaps influence the switching efficiency of PsD holes for mattertronic circuitry manipulation and separation. Moreover, single PsD holes are stored at each potential well as in an electrical storage capacitor, preventing multiple occupancies of PsD holes in the array of individual compartments due to magnetic Coulomb-like interaction. This approach may enable the development of large programmable arrays of label-free matters with high throughput, efficiency, and reliability as multiplex cell research platforms.

LRRC19 Promotes Permeability of the Gut Epithelial Barrier Through Degrading PKC-ζ and PKCι/λ to Reduce Expression of ZO1, ZO3, and Occludin.

A dysfunctional gut epithelial barrier allows the augmented permeation of endotoxins, luminal antigens, and bacteria into the bloodstream, causing disease. The maintenance of gut epithelial barrier integrity may be regulated by multiple factors. Herein we analyze the role of leucine-rich repeat-containing protein 19 (LRRC19) in regulating the permeability of the gut epithelial barrier. We utilized Lrrc19 knockout (KO) mice and clinical samples through transmission electron, intestinal permeability assay, Western blot, and immunofluorescence staining to characterize the role of LRRC19 in the permeability of the gut epithelial barrier. We found that LRRC19, which is expressed in gut epithelial cells, impairs gut barrier function. Transmission electron micrographs revealed a tighter junction and narrower gaps in the colon epithelium cells in LRRC19 KO mice. There were lower levels of serum lipopolysaccharide and 4 kDa-fluorescein isothiocyanate-dextran after gavage in LRRC19 KO mice than in wild-type mice. We found that LRRC19 could reduce the expression of zonula occludens (ZO)-1, ZO-3, and occludin in the colonic epithelial cells. The decreased expression of ZO-1, ZO-3, and occludin was dependent on degrading protein kinase C (PKC) ζ and PKCι/λ through K48 ubiquitination by LRRC19. The expression of LRRC19 was also negatively correlated with ZO-1, ZO-3, occludin, PKCζ, and PKCι/λ in human colorectal cancers. The protein LRRC19 can promote the permeability of the gut epithelial barrier through degrading PKC ζ and PKCι/λ to reduce the expression of ZO-1, ZO-3, and occludin.

Evaluation of the Attenuation Rate for Clinical Application of a Flexible Skin Dosimeter in Radiotherapy

During radiotherapy, some patients owing to the variability in skin sensitivities, may experience adverse skin reactions for doses at which other patients are asymptomatic. Hence, when abnormal symptoms appear on a patient’s skin, the etiology should be verified. Accordingly, a surface dosimeter on the skin can help ascertain whether accurate doses are irradiated. Furthermore, surface doses are measured in the field junction gaps during craniospinal irradiation or during large-area radiotherapy to avoid adverse reactions due to cumulative skin doses from multiple beams. However, the point dose measurement errors of surface dosimeters exceed approximately 10% and have low-positional accuracies because the attachment sites are approximated with the help of the naked eye. Moreover, accurate information on field junction gaps cannot be obtained. Therefore, in clinical practice, a flexible array dosimeter is required as it can measure the dose distribution on the body surface by adapting its shape to the body curvatures. In this study, we implemented a flexible array dosimeter and, based on its constituent materials, evaluated the attenuation rate associated with its use. A polyester (PET) film was used as the underlying substrate. HgI2 and PbI2 photoconductors were used for their good performances in films. Furthermore, the measurement accuracy was verified through comparisons with Monte Carlo simulation outcomes. The resulting PET film had an attenuation rate of 2.22% at a 50-µm thickness. At the minimum material thickness of 25 µm, the attenuation rates for HgI2 and PbI2 were 4.69% and 5.72%, respectively. Further research is needed to fabricate HgI2-based digital skin dosimeters with a thickness under 25 µm. Radiation detection and pixel resolution should be evaluated to accurately confirm the field junction gap.

Effect of miR-26b on gestational diabetes mellitus in rats via PI3K/Akt signaling pathway.

The aim of this study was to explore the influence of micro ribonucleic acid (miR)-26b on gestational diabetes mellitus in rats via the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathway. A total of 60 healthy pregnant female rats were randomly divided into three groups, including group A (normal group), group B (model group), and group C (model + miR-26b group). The differences in fasting blood glucose (FBG), C-reactive protein (CRP), and phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) among the three groups were analyzed via serum CRP test, morphological observation, quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and Western blotting, respectively. The levels of FBG ad CRP were significantly up-regulated in group B when compared with group A (p<0.01). Meanwhile, they increased significantly in group C when compared with group B (p<0.01). Rats in group A exhibited smooth and flat thoracic aortic intimas, as well as neatly arranged smooth muscle cells at the media layer. However, rats in group B showed fractured intimas with enlarged junction gaps, as well as necrotic and detached endothelial cells. Compared with group B, group C exhibited extremely poorly arranged cells at all the layers, rough and rugged intimas, larger areas of necrotic and detached endothelial cells, and markedly worsened lesions. QRT-PCR results indicated that the expression of phosphorylated-PI3K (p-PI3K) was significantly lower in group B than that of group A (p=0.04). Meanwhile, it was markedly lower in group C than that in group B (p=0.04). The expression of p-Akt was remarkably lower in group B than group A (p=0.04), which was also significantly lower in group C than group B (p=0.04). Compared with group A, the expressions of p-PI3K and p-Akt in the thoracic aorta of group B were evidently down-regulated (p<0.01). Furthermore, they decreased markedly in group C when compared with group B (p<0.01). MiR-26b accelerates the progression of gestational diabetes by inhibiting the PI3K/Akt signaling pathway.

Ginkgo biloba extract improves brain uptake of ginsenosides by increasing blood-brain barrier permeability via activating A1 adenosine receptor signaling pathway.

Ginkgo biloba leaves and Panax ginseng are Chinese medicine commonly used in combination for cerebral disease. To investigate the effect of standard extract of Ginkgo biloba leaves (EGb) on facilitating brain uptake of ginsenoside and its underlying mechanisms. The increasing uptake of ginsenosides in the brain of rats by EGb were detected by LC-MS/MS analysis. Evans blue and FITC-dextran leakage were determined to evaluate blood-brain barrier (BBB) permeability in vivo. Transendothelial electrical resistance (TEER) and Na-F penetration rate were measured with a co-culture of the human cerebral microvascular endothelial cell line (hCMEC/D3) and human normal glial cell line (HEB) in vitro BBB model. WB were used to analyzed the expression of BBB tight junctions (TJs) related protein (ZO-1, Occludin, Claudin-3, p-ERM, and p-MLC), ultrastructure of TJs was determined by transmission electron microscope. LC-MS/MS analysis demonstrated that EGb could improve brain uptake of ginsenoside Rg1, Re, Rd and Rb1. In vivo study showed that, BBB permeability was significantly increased after EGb administration, evidenced by the markedly increased penetration of FITC-dextran and Evans Blue into the mice brain parenchyma. In the in vitro BBB model, reduced TEER and increased Na-F penetration rate was observed in EGb group, which was associated with alteration of TJs ultrastructure. Furthermore, the expression of p-ERM and p-MLC in hCMEC/D3 as well as mice brain microvessels were significantly upregulated, but no significant change on the expression of TJs proteins (ZO-1, Occludin and Claudin-3). Moreover, the effect of EGb on in vitro BBB permeability and ERM, MLC phosphorylation was counteracted by DPCPX, an A1 adenosine receptor (A1R) antagonist. EGb might induce ERM/MLC phosphorylation and increase the cell-cell junction gaps to cause a reversible increase of the BBB permeability via A1R signaling pathway. Our results may contribute to better use of EGb in the treatment of brain diseases.

A compact microfluidic chip with integrated impedance biosensor for protein preconcentration and detection.

In this study, a low-cost, compact biochip is designed and fabricated for protein detection. Nanofractures formed by self-assembled gold nanoparticles at junction gaps are applied for ion enrichment and depletion to create a trapping zone when electroosmotic flow occurs in microchannels. An impedance measurement module is implemented based on the lock-in amplifier technique to measure the impedance change during antibody growth on the gold electrodes which is caused by trapped proteins in the detection region. The impedance measurement results confirm the presence of trapped proteins. Distinguishable impedance profiles, measured at frequencies in the range of 10-100 kHz, for the detection area taken before and after the presence of proteins validate the performance of the proposed system.

Entrainment, retention, and transport of freely swimming fish in junction gaps between commercial barges operating on the Illinois Waterway

Abstract Large Electric Dispersal Barriers were constructed in the Chicago Sanitary and Ship Canal (CSSC) to prevent the transfer of invasive fish species between the Mississippi River Basin and the Great Lakes Basin while simultaneously allowing the passage of commercial barge traffic. We investigated the potential for entrainment, retention, and transport of freely swimming fish within large gaps (> 50 m3) created at junction points between barges. Modified mark and capture trials were employed to assess fish entrainment, retention, and transport by barge tows. A multi-beam sonar system enabled estimation of fish abundance within barge junction gaps. Barges were also instrumented with acoustic Doppler velocity meters to map the velocity distribution in the water surrounding the barge and in the gap formed at the junction of two barges. Results indicate that the water inside the gap can move upstream with a barge tow at speeds near the barge tow travel speed. Water within 1 m to the side of the barge junction gaps was observed to move upstream with the barge tow. Observed transverse and vertical water velocities suggest pathways by which fish may potentially be entrained into barge junction gaps. Results of mark and capture trials provide direct evidence that small fish can become entrained by barges, retained within junction gaps, and transported over distances of at least 15.5 km. Fish entrained within the barge junction gap were retained in that space as the barge tow transited through locks and the Electric Dispersal Barriers, which would be expected to impede fish movement upstream.

SU‐F‐E‐20: A Mathematical Model of Linac Jaw Calibration Integrated with Collimator Walkout

Purpose:Accurate jaw calibration is possible, but it does not necessarily achieve good junctions because of collimator rotation walkout. We developed a mathematical model seeking to pick an origin for calibration that minimizes the collimator walkout effect.Methods:We use radioopaque markers aligned with crosshair on the EPID to determine the collimator walkout at collimator angles 0°, 90° and 270°. We can accurately calibrate jaws to any arbitrary origin near the radiation field centre. While the absolute position of an origin moves with the collimator walkout, its relative location to the crosshair is an invariant. We studied two approaches to select an optimal origin. One approach seeks to bring all three origin locations (0°–90°–270°) as close as possible by minimizing the perimeter of the triangle formed by these points. The other approach focuses on the gap for 0°–90° junctions.Results:Our perimeter cost function has two variables and non‐linear behaviour. Generally, it does not have zero‐perimeter‐length solution which leads to perfect jaw matches. The zero solution can only be achieved, if the collimator rotates about a single fixed axis. In the second approach, we can always get perfect 0°–0° and 0°–90° junctions, because we ignore the 0°–270° situation. For our TrueBeams, both techniques for selecting an origin improved junction dose inhomogeneities to less than ±6%.Conclusion:Our model considers the general jaw matching with collimator rotations and proposes two potential solutions. One solution optimizes the junction gaps by considering all three collimator angles while the other only considers 0°–90°. The first solution will not give perfect matching, but can be clinically acceptable with minimized collimator walkout effect, while the second can have perfect junctions at the expense of the 0°–270° junctions. Different clinics might choose between these two methods basing on their clinical practices.

Enhancement of Tumor-Targeted Delivery of Bacteria with Nitroglycerin Involving Augmentation of the EPR Effect.

The use of bacteria, about 1 μm in size, is now becoming an attractive strategy for cancer treatment. Solid tumors exhibit the enhanced permeability and retention (EPR) effect for biocompatible macromolecules such as polymer-conjugated anticancer agents, liposomes, and micelles. This phenomenon permits tumor-selective delivery of such macromolecules. We report here that bacteria injected intravenously evidenced a property similar to that can of these macromolecules. Bacteria that can accumulate selectively in tumors may therefore be used in cancer treatment.Facultative or anaerobic bacteria will grow even under the hypoxic conditions present in solid tumors. We found earlier that nitric oxide (NO) was among the most important factors that facilitated the EPR effect via vasodilatation, opening of endothelial cell junction gaps, and increasing the blood flow of hypovascular tumors. Here, we describe the augmentation of the EPR effect by means of nitroglycerin (NG), a commonly used NO donor, using various macromolecular agents in different tumor models. More importantly, we report that NG significantly enhanced the delivery of Lactobacillus casei to tumors after intravenous injection of the bacteria, more than a tenfold increase in bacterial accumulation in tumors after NG treatment. This finding suggests that NG has a potential advantage to enhance bacterial therapy of cancer, and further investigations of this possibility are warranted.

Calculating electronic tunnel currents in networks of disordered irregularly shaped nanoparticles by mapping networks to arrays of parallel nonlinear resistors

We have shown both theoretically and experimentally that tunnel currents in networks of disordered irregularly shaped nanoparticles (NPs) can be calculated by considering the networks as arrays of parallel nonlinear resistors. Each resistor is described by a one-dimensional or a two-dimensional array of equal size nanoparticles that the tunnel junction gaps between nanoparticles in each resistor is assumed to be equal. The number of tunnel junctions between two contact electrodes and the tunnel junction gaps between nanoparticles are found to be functions of Coulomb blockade energies. In addition, the tunnel barriers between nanoparticles were considered to be tilted at high voltages. Furthermore, the role of thermal expansion coefficient of the tunnel junction gaps on the tunnel current is taken into account. The model calculations fit very well to the experimental data of a network of disordered gold nanoparticles, a forest of multi-wall carbon nanotubes, and a network of few-layer graphene nanoplates over a wide temperature range (5-300 K) at low and high DC bias voltages (0.001 mV–50 V). Our investigations indicate, although electron cotunneling in networks of disordered irregularly shaped NPs may occur, non-Arrhenius behavior at low temperatures cannot be described by the cotunneling model due to size distribution in the networks and irregular shape of nanoparticles. Non-Arrhenius behavior of the samples at zero bias voltage limit was attributed to the disorder in the samples. Unlike the electron cotunneling model, we found that the crossover from Arrhenius to non-Arrhenius behavior occurs at two temperatures, one at a high temperature and the other at a low temperature.

Protein preconcentration using nanofractures generated by nanoparticle-assisted electric breakdown at junction gaps.

Sample preconcentration is an important step that increases the accuracy of subsequent detection, especially for samples with extremely low concentrations. Due to the overlapping of electrical double layers in the nanofluidic channel, the concentration polarization effect can be generated by applying an electric field. Therefore, a nonlinear electrokinetic flow is induced, which results in the fast accumulation of proteins in front of the induced ionic depletion zone, the so-called exclusion-enrichment effect. Nanofractures were created in this work to preconcentrate proteins via the exclusion-enrichment effect. The protein sample was driven by electroosmotic flow and accumulated at a specific location. The preconcentration chip for proteins was fabricated using simple standard soft lithography with a polydimethylsiloxane replica. Nanofractures were formed by utilizing nanoparticle-assisted electric breakdown. The proposed method for nanofracture formation that utilizes nanoparticle deposition at the junction gap between microchannels greatly decreases the required electric breakdown voltage. The experimental results indicate that a protein sample with an extremely low concentration of 1 nM was concentrated to 1.5×104-fold in 60 min using the proposed chip.

An investigation on piezoresistive behavior of carbon nanotube/polymer composites: II. Positive piezoresistive effect

Due to the diversity of carbon nanotubes (CNTs), polymers, and the preparation processes of the composites, CNT-filled polymeric composites present various piezoresistive properties. One puzzling issue is the concurrence of a negative piezoresistive effect and a positive piezoresistive effect in composites with different polymer matrixes. In this paper, we present a microscopic view of the nature of the positive piezoresistive effect and its dependence on the polymer matrix types based on the model in our previous study, in which the piezoresistive behavior was tailored by a parameter—the average junction gap variation (AJGV)—describing the statistical property of the CNT conductive network. The microscopic movement process of CNTs embedded in a polymer matrix was analyzed and then the Poisson’s ratio of the polymer matrix was determined as a key factor that is in charge of negative or positive piezoresistive properties. The obstacle effect of polymer chains on the movement of CNTs was also found to be responsible for the positive piezoresistive effect as it affects the AJGV in compressive strain. Based on numerical simulations of CNT network deformation with different Poisson’s ratios and minimum junction gaps caused by the obstacle effect, the positive piezoresistive effect was found resulted from the obstacle effect on CNT junction gap variations that exceeds the initial value of the AJGV caused by the CNT network deformation, and only occur under the precondition of the polymer matrixes with a large Poisson’s ratio close to 0.5. The conclusions were then verified experimentally using composites with two kinds of polymer matrixes with significantly different Poisson’s ratios.

The four mechanisms of dental resorption initiation

The aim of this study is to present a classification with a clinical application for root resorption, so that diagnosis will be more objective and immediately linked to the source of the problem, leading the clinician to automatically develop the likely treatment plan with a precise prognosis. With this purpose, we suggest putting together all diagnosed dental resorptions into one of these four criteria: 1) Root resorption caused by cementoblast cell death, with preservation of the Malassez epithelial rests. 2) Root resorption by cementoblasts and Malassez epithelial rests death. 3) Dental resorption by odontoblasts cell death with preservation of pulp vitality. 4) Dental resorption by direct exposure of dentin to gingival connective tissue at the cementoenamel junction gaps.

Electron transport in discontinuous gold films and the effect of Coulomb blockade and percolation

Understanding the electron transport in disordered assemblies of weakly coupled nano-sized metal clusters is important for many applications. Here, we investigate experimentally and theoretically the electron transport properties of metal cluster assemblies in the form of discontinuous gold films. Discontinuous films of different average island size are produced by sputter deposition, and the resistance and the non-linear current-voltage (I-V) characteristics of the films are measured as a function of temperature. To interpret the experimental electron transport data, a conduction percolation model is employed where broad probability distributions for both the tunnel junction gaps and the Coulomb blockade energies are used. Excellent agreement between experimental data and model calculations is found. In particular, the non-Arrhenius resistive behavior, the I-V power-law behavior, and the I-V characteristics at large bias voltage are all shown to be due to a conduction percolation mechanism governing disordered networks of nano-sized metal islands connected by tunnel junctions.

A Cell- Surface Polymer Reptation Mechanism for Tumor Transendothelial Transport of Macromolecules

Polymer reptation is a process by which flexible linear polymers can migrate around obstacles and through pores and around other polymer molecules. It has successfully described quantitative behavior of polymer melts and has been invoked in explaining DNA separation according to length in sequencing gels. This mechanism may therefore be useful in delivering contrast agents or therapeutic drugs to tumors as these must traverse from the intravascular space through the tumor endothelial junction gaps and into the tumor. In this work, we show that polymers capable of weak interactions with tumor endothelium can translocate into the tumor interstitium at up to 9 times the rate of polymers without such cell-surface interactions. We propose a new mechanism by which the polymers diffuse along the cell surface and through cell junction gaps that occur in the tumor endothelium. This process can be halted in a number of ways that demonstrate that the surface interaction is essential for the higher transport rate. Alternative transport mechanisms are ruled out by further tests of polymer length scaling dependence, and by comparison of transport rates to those for globular constructs. Polymers of Gd-DTPA-polylysine and related backbones were investigated in an animal model of breast cancer and prostate cancer. Polymer lengths ranged from 30 nm to 300 nm, (from 100 to 700 lysine residues) and the polymer constructs had a cross section of approximately 1.2 nm in radius. Polymer uptake rate into tumors for an equivalent hydrodynamic size globular macromolecule was some 135 times larger demonstrating the importance of this transport mechanism compared to free diffusion of globular macromolecules through the endothelium junction pores. The polymer length scaling, with monomer number N, on rate of tumor transport goes as N(-1), which rejects alternative transport processes such as pinocytosis, active transport, and particle like center of mass diffusion through pores. This N(-1) scaling implies a cell-surface assisted polymer reptation process. This new transport mechanism allows very strong discrimination of aggressive tumors from nonaggressive tumors in animal model studies.

Analysis of Waveguide Junction Discontinuities and Gaps Using Finite Element Method

A Finite Element Method (FEM) is presented to determine reflection and transmission coefficients of rectangular waveguide junction discontinuities. H-, E- plane discontinuities in a concentric/non concentric rectangular waveguide junction are analyzed using the FEM procedure. Also, reflection and transmission coefficients due to presence of a gap between two sections of a rectangular waveguide are determined using the FEM. The numerical results obtained using the FEM procedure are compared with results obtained using the Mode Matching Method (MMM) and with measured data.