Leak Channel Research Articles

MOLECULAR MECHANISMS OF NOCICEPTION IN CHRONIC PROSTATITIS

Introduction. The need to understand the pathophysiology of prostatitis is determined by its prevalence, usually chronic progressive course, significant impact on quality of life, fertility and sexuality. The modern arsenal of medicines allows us to achieve a clinically significant effect. Along with this, non-pharmacological methods are widely used to increase the effectiveness of treatment. However, despite significant successes in the treatment of prostatitis, the problems of insufficient efficiency remain unsolved by modern urology, and it is extremely difficult to help these patients. Understanding the pathophysiology of the disease has always been the key to successful diagnosis and treatment. That is why it is important to determine the mechanisms of development of painful manifestations of prostatitis.
 The aim. To describe the main molecular mechanisms of tissue damage reception, in particular of the prostate gland, which are perceived as pain sensations.
 Materials and methods. An evaluation of modern literature devoted to the mechanisms of creation of nerve impulses due to damage and inflammation of the prostate gland was carried out. The search was conducted in the MEDLINE and databases of the National Library of Ukraine named after V.I. Vernadsky.
 Results. The main molecular mechanisms of nociception in chronic prostatitis have been determined. A review of modern literature devoted to the study of pain mechanisms as a biologically significant signal of damage at the molecular level of reception is presented. Attention is focused on the features of nociception in prostatitis, its connection with the production of inflammatory mediators, possible mechanisms of hyperalgesia and allodynia.
 As a result of stress and tissue damage, the production and release of inflammatory mediators such as interleukins, interferon, prostaglandins, bradykinin, adenosine triphosphate, protons and nerve growth factor increase. These mediators activate pain receptors located on nerve endings and are ion channels of various types: transient receptor potential, acid, purinergic, and potassium ion leak channels.
 Conclusions. The presented literature data describe the mechanisms of nociception, hyperalgesia and allodynia in chronic prostatitis, the understanding of which can be the basis for the development of new methods of diagnosis and treatment.

Potassium Leak Channels and Mitochondrial Complex I Interact in Glutamatergic Interneurons of the Mouse Spinal Cord.

Volatile anesthetics induce hyperpolarizing potassium currents in spinal cord neurons that may contribute to their mechanism of action. They are induced at lower concentrations of isoflurane in noncholinergic neurons from mice carrying a loss-of-function mutation of the Ndufs4 gene, required for mitochondrial complex I function. The yeast NADH dehydrogenase enzyme, NDi1, can restore mitochondrial function in the absence of normal complex I activity, and gain-of-function Ndi1 transgenic mice are resistant to volatile anesthetics. The authors tested whether NDi1 would reduce the hyperpolarization caused by isoflurane in neurons from Ndufs4 and wild-type mice. Since volatile anesthetic behavioral hypersensitivity in Ndufs4 is transduced uniquely by glutamatergic neurons, it was also tested whether these currents were also unique to glutamatergic neurons in the Ndufs4 spinal cord. Spinal cord neurons from wild-type, NDi1, and Ndufs4 mice were patch clamped to characterize isoflurane sensitive currents. Neuron types were marked using fluorescent markers for cholinergic, glutamatergic, and γ-aminobutyric acid-mediated (GABAergic) neurons. Norfluoxetine was used to identify potassium channel type. Neuron type-specific Ndufs4 knockout animals were generated using type-specific Cre-recombinase with floxed Ndufs4. Resting membrane potentials (RMPs) of neurons from NDi1;Ndufs4, unlike those from Ndufs4, were not hyperpolarized by 0.6% isoflurane (Ndufs4, ΔRMP -8.2 mV [-10 to -6.6]; P = 1.3e-07; Ndi1;Ndufs4, ΔRMP -2.1 mV [-7.6 to +1.4]; P = 1). Neurons from NDi1 animals in a wild-type background were not hyperpolarized by 1.8% isoflurane (wild-type, ΔRMP, -5.2 mV [-7.3 to -3.2]; P = 0.00057; Ndi1, ΔRMP, 0.6 mV [-1.7 to 3.2]; P = 0.68). In spinal cord slices from global Ndufs4 animals, holding currents (HC) were induced by 0.6% isoflurane in both GABAergic (ΔHC, 81.3 pA [61.7 to 101.4]; P = 2.6e-05) and glutamatergic (ΔHC, 101.2 pA [63.0 to 146.2]; P = 0.0076) neurons. In neuron type-specific Ndufs4 knockouts, HCs were increased in cholinergic (ΔHC, 119.5 pA [82.3 to 156.7]; P = 0.00019) and trended toward increase in glutamatergic (ΔHC, 85.5 pA [49 to 126.9]; P = 0.064) neurons but not in GABAergic neurons. Bypassing complex I by overexpression of NDi1 eliminates increases in potassium currents induced by isoflurane in the spinal cord. The isoflurane-induced potassium currents in glutamatergic neurons represent a potential downstream mechanism of complex I inhibition in determining minimum alveolar concentration.

Development of the automated decision-making system synthesis method in the management of information security channels

In the process of transmission channels functioning, the results of the work of bodies for detecting and blocking information leakage channels are not sufficiently taken into account. Management of information protection channels is actually the collection and display of data followed by the assignment of influence on each information channel separately and is carried out in manual mode. In decision support systems, the tasks of identifying information leakage channels are not solved. There is a contradiction between the requirements for the automation of the management of information protection channels and the possibility of meeting these requirements at the expense of the available automation tools. Classical theory considers the decision-making process as a choice of one of many alternatives. The development of rational forms and methods of managing information protection channels should prevent threats and challenges. Therefore, the object of research is the process of ensuring security during data transmission through information channels. The main threats and challenges are man-made and natural cataclysms, terrorism, aggression by a number of states or individual groups of people, which are not taken into account in the complex in the decision-making system during the management of information protection channels. A structural diagram of information exchange based on the description of a weakly formalized process under conditions of non-stochastic uncertainty is proposed. It is proposed to use the logical-linguistic production model. For a hierarchically organized structure based on classification features, it is proposed to build a hierarchy tree that takes into account the relationships of partially ordered sets. The formed production rules for determining appropriate strategies for the planned detection of information leakage channels based on predicted values allow to proceed to knowledge processing for the synthesis of an automated decision-making system during the management of protection channels

Application of Fast Fourier Transform to the Speech Signals Scrambling

The article is devoted to the closure of speech signals by implementing a fast Fourier transform in a bandpass scrambler. The most radical measure to prevent the interception of speech signals is the use of cryptographic security methods. The first technical security systems began to be developed immediately after the invention of the telephone. The main goal when developing speech transmission systems is to preserve those characteristics that are most important for the listener to perceive. Communication security in the transmission of voice messages is based on the use of a large number of different methods of blocking signals that change the characteristics of speech in such a way that it becomes illegible and unrecognizable to attackers who listen to or intercept the closed voice message. The choice of closure methods depends on the specific application and the technical characteristics of the transmission channel. That is, technical channels of information leakage are a source of information for technical intelligence, which extracts information using technical means. Therefore, the problem of protecting information from technical intelligence is of particular relevance. The object of the study is the transmission of voice messages. The subject of the research is real-time speech closing systems. The purpose of the paper is to use fast Fourier transform to close speech signals in a bandpass scrambler. To do this, it is necessary to assess the capabilities of technical intelligence to intercept information of limited distribution; analyze types of speech signal closing systems.
 The paper presents a block diagram of a combined scrambler, an algorithm for rearranging input signal values using the fast Fourier transform, and hashing functions that are used to obtain a speech signal from a combined scrambler. It has been determined that "through-window" scramblers are the most reliable, and for greater levels of closure, combination scramblers should be used. The task set for further development of the topic is the development of a software application for the operation of streaming data encryption methods in real time.

Ultrasound-Induced Membrane Hyperpolarization in Motor Axons and Muscle Fibers of the Crayfish Neuromuscular Junction.

Focused ultrasound (FUS) can modulate neuronal activity by depolarization or hyperpolarization. Although FUS-evoked depolarization has been studied extensively, the mechanisms underlying FUS-evoked hyperpolarization (FUSH) have received little attention. In the study described here, we developed a procedure using FUS to selectively hyperpolarize motor axons in crayfish. As a previous study had reported that these axons express mechano- and thermosensitive two-pore domain potassium (K2P) channels, we tested the hypothesis that K2P channels underlie FUSH. Intracellular recordings from a motor axon and a muscle fiber were obtained simultaneously from the crayfish opener neuromuscular preparation. FUSH was examined while K2P channel activities were modulated by varying temperature or by K2P channel blockers. FUSH in the axons did not exhibit a coherent temperature dependence, consistent with predicted K2P channel behavior, although changes in the resting membrane potential of the same axons indicated well-behaved K2P channel temperature dependence. The same conclusion was supported by pharmacological data; namely, FUSH was not suppressed by K2P channel blockers. Comparison between the FUS-evoked responses recorded in motor axons and muscle fibers revealed that the latter exhibited very little FUSH, indicating that the FUSH was specific to the axons. It is not likely that K2P channels are the underlying mechanism for FUSH in motor axons. Alternative mechanisms such as sonophore and axon-specific potassium channels were considered. Although the sonophore hypothesis could account for electrophysiological features of axonal recordings, it is not consistent with the lack of FUSH in muscle fibers. An axon-specific and mechanosensitive potassium channel is also a possible explanation.

Three-dimensional Response Characteristics of Self-potential Field for Dam Leakage Hidden Danger

In order to improve the application of self-potential field monitoring in detecting the potential reservoir dam leakage, we deduced the coupling equation of the self-potential field with water flow field and ions diffusion field, based on the formation mechanism of the self-potential field. We realized the three-dimensional numerical simulation of the self-potential field of reservoir dam by coupling finite and infinite elements by analyzing the response characteristics of the self-potential field with different water levels, different levels of danger, and different periods of typical dam leakage models. The results show that the magnitude of the self-potential field is proportional to the size of the leakage channel and the magnitude of water level difference. Thus, the distribution characteristics of the self-potential field could indicate the development period of a leakage to some extent, and the leakage location and early warning could be realized by monitoring self-potential fields.

Enhanced the performance of CZTSSe solar cells by optimized i:ZnO window layer

We have systematically investigated the effect of i:ZnO window layer with different thickness on the performance of CZTSSe solar cells. The i:ZnO films were deposited on SLG substrate by adjusting the supttering time, and the accurate thickness was determined by XRR spectra. GIXRD, AFM images and absorption spectra show that the crystalline quality is stable and increases with the increase of thickness, while transmittivity declines. Furthermore, CZTSSe solar cells with the structure of SLG/Mo/CZTSSe/CdS/i:ZnO/ITO/Al were fabricated. It is found that Voc and FF of solar cell are affected by the thickness of i:ZnO layer obviously. The i:ZnO window layer plays an important role in reducing the channels of current leakage. Meanwhile, a compromise among the parallel conductance, series resistance and transmittivity are needed. By optimized the process, the efficiency of CZTSSe solar cell was significantly improved to 10.74 % when the thickness of i:ZnO was about 26 nm.

The influence of the structure of guard rings on the dark currents of silicon p-i-n photodiodes

The article examines the influence of the guard rings (GR) system structure on the dark currents of responsive elements (RE) and the actual guard rings of silicon 4-element p-i-n photodiodes (PD). The samples were made on the basis of p-silicon by planar technology. Samples with one, two, and three GR were produced. It was found that increasing the amount of n+-GRs does not reduce the dark current of the REs. But with an increase in the number of n+-GRs, the probability of an edge breakdown of the n+-p-junction in the regions of the exit of the hetero-junction of the GR to the surface increases. It is possible to reduce the levels of dark current of REs and GR by combining n+- and p+- guard regions, where p+-GR is a region of restriction of dark current leakage channels, isotypic with the substrate material. PD was made with p+-GR on the periphery of the crystal in the form of a concentric ring, as well as with a p+- region on the entire periphery of the crystal. This makes it possible to reduce the level of of dark current of n+- GR due to the reduction of the area of collection of charge carriers from the surface. But a significant decrease in the dark current of REs was not observed in such cases. We proposed to carry out boron diffusion in the gaps between REs and between REs and n+-GR.

The transcription factor ETV1 regulates expression of the atrial specific potassium channel TASK-1 and modulates cardiac action potentials

Abstract Background In recent years, the two-pore domain potassium channel TASK-1 has been identified to play an important role in the pathophysiology of atrial fibrillation (AF). In cardiac tissue, TASK-1 is almost exclusively expressed in the atria and significantly upregulated in AF patients. Moreover, it has been characterized as a key player in action potential (AP) shortening observed during AF, making it a promising target for antiarrhythmic therapy. However, the underlying transcriptional mechanisms responsible for TASK-1 upregulation during AF are still unclear. A few years ago, the transcription factor ETV1 has been described to induce atrial remodeling and arrhythmia. Similar to TASK-1, ETV1 is predominantly expressed in the atria and upregulated in AF patients. Therefore, investigating possible interactions between ETV1 and TASK-1 is crucial to further understand atrial remodeling and develop new antiarrhythmic strategies. Purpose The purpose of this study was to investigate the effects of ETV1 regulation on TASK-1 expression. For that, electrophysiological effects of ETV1 modulation on TASK-1 currents and action potential formation were studied on HL-1 cardiomyocytes. Methods ETV1 modulation was achieved either through application of the pharmacological ETV1-inhibitor BRD32048 (1 µM) or transfection of HL-1 cells with a specific ETV1-siRNA. Electrophysiological effects of ETV1 inhibition were assessed using two-electrode voltage clamp experiments on Xenopus laevis oocytes heterologously expressing TASK-1 as well as whole-cell patch clamp measurements on HL-1 cells after pharmacological- and siRNA-mediated ETV1 inhibition. Chromatin immunoprecipitation combined with real-time qPCR (ChIP-qPCR) and ATAC-seq experiments were performed to identify the epigenetic interaction between ETV1 and the KCNK3 gene encoding TASK-1. Results TASK-1 currents were markedly reduced in Xenopus laevis oocytes after inhibition of ETV1. Furthermore, both pharmacological inhibition and siRNA-mediated knockdown of ETV1 caused a significant decrease of TASK-1 currents in HL-1 cells by 35.8% and 39.3%, respectively. These effects were associated with a statistically significant prolongation of the action potential duration at 90% repolarization (APD90) by 28.5% after functional inhibition and 24.9% after siRNA-knockdown. This correlated with a significant decrease of TASK-1 expression on mRNA and protein level. In addition, ATAC-seq data and ChIP-qPCR revealed an enrichment of ETV1 binding within accessible regulatory elements at the KCNK3 gene locus. Conclusions ETV1-knockdown shows strong inhibitory effects on TASK-1 while ChIP-qPCR and ATAC-seq data suggest that ETV1 acts as a direct transcriptional activator of KCNK3. The finding that ETV1 is involved in the regulation of TASK-1 improves our understanding of the pathomechanisms underlying AF and will hopefully help to advance TASK-1-based AF therapy.

K2P2.1 is a regulator of inflammatory cell responses in idiopathic inflammatory myopathies

K2P2.1 (TREK1), a two-pore domain potassium channel, has emerged as regulator of leukocyte transmigration into the central nervous system. In the context of skeletal muscle, immune cell infiltration constitutes the pathogenic hallmark of idiopathic inflammatory myopathies (IIMs). However, the underlying mechanisms remain to be elucidated. In this study, we investigated the role of K2P2.1 in the autoimmune response of IIMs. We detected K2P2.1 expression in primary skeletal muscle and endothelial cells of murine and human origin. We observed an increased pro-inflammatory cell response, adhesion and transmigration by pharmacological blockade or genetic deletion of K2P2.1 in vitro and in in vivo myositis mouse models. Of note, our findings were not restricted to endothelial cells as skeletal muscle cells with impaired K2P2.1 function also demonstrated a strong pro-inflammatory response. Conversely, these features were abrogated by activation of K2P2.1 and improved the disease course of a myositis mouse model. In humans, K2P2.1 expression was diminished in IIM patients compared to non-diseased controls arguing for the translatability of our findings. In summary, K2P2.1 may regulate the inflammatory response of skeletal muscle. Further research is required to understand whether K2P2.1 could serve as novel therapeutic target.

SEC61B Regulates Calcium Flux and Platelet Hyperactivity in Diabetes Mellitus

Background/Aim Platelets in individuals with diabetes mellitus show increased activity at baseline and in response to stimuli, which contributes to the increased cardiovascular events in this population. Endoplasmic reticulum (ER) stress, induced by misfolded proteins, has recently been identified as a mechanism of platelet hyperactivity in diabetes. Newly synthesized proteins enter the ER via the Sec61 translocon for folding. The Sec61 translocon is a heterotrimeric channel comprising of the pore-forming α, and peripheral β and γ subunits. In addition to its roles in proteostasis, it also acts as a leak channel to allow calcium efflux from the ER into the cytosol. However, a function for the Sec61 complex has not been previously described in platelets. Study design/Methods Platelets were isolated from 42 patients with and 34 patients without type 2 diabetes mellitus undergoing coronary angiography for suspected or known coronary artery disease. Patients were matched for age, sex, and coronary artery disease burden. Platelet proteins were identified by untargeted LC-MS/MS and analyzed by MaxQuant. Platelet RNA was isolated from a separate cohort of 5 patients with and 12 matched patients without type 2 diabetes. RNA-seq libraries were prepared with TruSeq V2, Illumina, and analyzed with the Deseq2 analysis package. Platelets and megakaryocytes were isolated from 2 mouse models of diabetes (Apoe-/- mice with induction of diabetes by streptozotocin injection) and outbred mice fed a high fat diet. HEK293 cells were generated with knockout or overexpression of SEC61B using CRISPR/Cas9 or cDNA transfection. Proteins of the ER stress response, including eukaryotic translation initiation factor 2A (EIF2A), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), were determined by immunoblotting or immunostaining. Protein synthesis was measured using the Click-iT TM AHA Alexa Fluor 488 assay. Calcium flux was measured using fura-2-AM and expressed as normalised fluorescent 340/380 nm ratio. Calcium efflux from the ER was measured in the presence of translation inhibitors puromycin and eeyarestatin I and the sarcoendoplasmic reticulum calcium-ATPase inhibitor thapsigargin. Results Proteomics analysis identified an enrichment of proteins involved in response to oxidative stress in platelets of patients with diabetes. From the over 2600 intracellular proteins identified consistently in >50% of human platelet samples, SEC61B was the only protein significantly and positively correlated with serum fructosamine, which is a marker of glycaemic control (Spearman's rho = 0.33, p = 0.029). SEC61B protein abundance was increased in platelets with high fructosamine (>290 µmol/L) compared with normal fructosamine ( panel A). There were no differences between SEC61 subunits in patients with or without diabetes at the transcriptomic level. Increased SEC61B was confirmed in platelets and megakaryocytes of hyperglycemic mice. Induction of ER stress in healthy human platelets by incubation with thapsigargin significantly increased the phosphorylation of IRE1 and the expression of SEC61B but not of ATF6 or phosphorylated EIF2A. In HEK293 cells with SEC61B overexpression or knockout, protein synthesis rate was decreased (58-72% reduction knockout vs control, p<0.0001; 22% reduction overexpression vs control, p = 0.0005). SEC61B overexpression or knockout resulted in increased ER calcium efflux after treatment with puromycin or eeyarestatin I (which maintain the Sec61 translocon in an open, calcium permeable configuration ( panel B). Puromycin induced ER-mediated calcium leak in healthy human platelets (22% increase in maximal calcium efflux after puromycin treatment, p = 0.039). Conclusion Our data identify Sec61 translocon as a novel functional ER calcium leak channel in platelets. Diabetes mellitus is associated with upregulated megakaryocyte and platelet SEC61B. Dysregulated SEC61B expression is associated with increased calcium efflux from the ER. We propose a mechanism whereby ER stress-induced upregulation of platelet SEC61B leads to increased cytoplasmic calcium, potentially contributing to the platelet hyperactivity seen in diabetes mellitus.

FFT-Based Numerical Method for Nonlinear Elastic Contact

In theoretical research pertaining to sealing, a contact model must be used to obtain the leakage channel. However, for elastoplastic contact, current numerical methods require a long calculation time. Hyperelastic contact is typically simplified to a linear elastic contact problem, which must be improved in terms of calculation accuracy. Based on the fast Fourier transform, a numerical method suitable for elastoplastic and hyperelastic frictionless contact that can be used for solving two-dimensional and three-dimensional (3D) contact problems is proposed herein. The nonlinear elastic contact problem is converted into a linear elastic contact problem considering residual deformation (or the equivalent residual deformation). Results from numerical simulations for elastic, elastoplastic, and hyperelastic contact between a hemisphere and a rigid plane are compared with those obtained using the finite element method to verify the accuracy of the numerical method. Compared with the existing elastoplastic contact numerical methods, the proposed method achieves a higher calculation efficiency while ensuring a certain calculation accuracy (i.e., the pressure error does not exceed 15%, whereas the calculation time does not exceed 10 min in a 64 × 64 grid). For hyperelastic contact, the proposed method reduces the dependence of the approximation result on the load, as in a linear elastic approximation. Finally, using the sealing application as an example, the contact and leakage rates between complicated 3D rough surfaces are calculated. Despite a certain error, the simplified numerical method yields a better approximation result than the linear elastic contact approximation. Additionally, the result can be used as fast solutions in engineering applications.

Targeting parvalbumin-expressing neurons in the substantia nigra pars reticulata restores motor function in parkinsonian mice

The activity of substantia nigra pars reticulata (SNr) neurons, the main output structure of basal ganglia, is altered in Parkinson's disease (PD). However, neither the underlying mechanisms nor the type of neurons responsible for PD-related motor dysfunctions have been elucidated yet. Here, we show that parvalbumin-expressing SNr neurons (SNr-PV+) occupy dorsolateral parts and possess specific electrophysiological properties compared with other SNr cells. We also report that only SNr-PV+ neurons' intrinsic excitability is reduced by downregulation of sodium leak channels in a PD mouse model. Interestingly, in anesthetized parkinsonian mice invivo, SNr-PV+ neurons display a bursty pattern of activity dependent on glutamatergic tone. Finally, we demonstrate that chemogenetic inhibition of SNr-PV+ neurons is sufficient to alleviate motor impairments in parkinsonian mice. Overall, our findings establish cell-type-specific dysfunction in experimental parkinsonism in the SNr and provide a potential cellular therapeutic target to alleviate motor symptoms in PD.

Research Progress of Drilling and Completion Fluid Loss Model in Fractured Reservoir

Well loss and its accompanying reservoir damage is a common and serious problem, which not only greatly restricts the economic benefit, but also seriously affects the correct evaluation of reservoir oil and gas resources in the early stage of exploration. With the exploration and development of deep Marine carbonate oil and gas resources, fracture leakage has gradually become a frontier and hot issue to be studied urgently. Foreign scholars began to study the leakage model of fractured reservoir in the 1990s, but at present, domestic scholars mainly focus on the clastic rock model, focusing on the plugging technology and plugging materials, while ignoring the importance of the dynamic development of the leakage indirectly reflecting the leakage type and the size of the leakage channel. This paper comprehensively analyses the effects of drilling completion fluid rheology, fracture opening variation, fracture wall filtration and other factors on well loss from the time sequence of the establishment of the leakage model, summarizes the research progress of the mathematical model of leakage in fractured reservoirs, and proposes to pay attention to and strengthen the monitoring of the leakage mechanism and the dynamic process of leakage, so as to provide a theoretical basis for the rapid diagnosis of leakage types and the optimization of leakage control.

Different reverse leakage current transport mechanisms of planar Schottky barrier diodes(SBDs) on sapphire and GaN substrate

The effects of different substrates on the off-state leakage current in gallium nitride (GaN) planar diodes are experimentally demonstrated and studied by analyzing temperature-dependent current–voltage characteristics. The two devices exhibit different leakage mechanisms despite being subjected to the same process conditions. The device with a sapphire substrate shows a more intricate leakage mechanism, implying the presence of additional leakage channels compared to the device with free-standing substrates. The electrical leakage characteristics in the planar GaN-on-sapphire device (referred to as utemp-SBD) and GaN substrate device (referred to as usub-SBD) Schottky barrier diodes (SBD) can be described by two distinct processes as the reverse bias gradually increases: utemp-SBD go through the thermionic emission (TE), variable range hopping (VRH), Frenkel–Poole (FP) emission and space-charge-limited conduction (SCLC) model; The leakage conduction mechanism of usub-SBD include TE, VRH, and FP emission mechanisms. It is noteworthy that in device 1, there is a rapid increase in leakage current within the voltage range of −36 to −40 V, primarily driven by the SCLC mechanism. This effect arises due to the presence of intrinsic traps in GaN grown on a heterogeneous substrate. Additionally, in the voltage range of −7 to −50 V (348 K to 448 K), the leakage mechanism shifts from FP emission to the VRH model, possibly due to variations in the Schottky barrier height.This study provides an in-depth analysis of the leakage mechanisms observed on different substrates and offers valuable insights for the design of planar gate transistors to minimize or avoid the occurrence of leakage channels.

Isolation of Responsive Elements of Planar Multi-Element Photodiodes

In the mass production of multi-element silicon p-i-n photodiodes, the problem of systematic rejection of products due to a decrease in the insulation resistance between the active elements of photodetectors has been revealed. The purpose of this work is to study the causes of insulation resistance degradation and to establish optimal methods for avoiding this phenomenon. A comparative analysis of three insulation methods was carried out: classical insulation by the surface of a non-conductive substrate and a dielectric layer; insulation by means of mesaprofile grooves with a dielectric film; insulation by means of areas of limitation of surface leakage channels isotypic with the substrate material (in this case, p+-type) formed in the gaps between active elements. The study found that the reason for the deterioration of the insulation resistance between the active elements of photodiodes is the presence of conductive inversion channels at the Si-SiO2 interface due to the use of silicon with high resistivity. One mechanism for the formation of inversion channels is the redistribution of impurities in the masking oxide (in particular, phosphorus) and their diffusion to the interface during thermal operations. Another mechanism for the formation of inversion layers is the diffusion of boron from silicon into SiO2 during heat treatment due to the fact that the boron segregation coefficient is less than one. In the manufacture of samples with insulation using non-conductive areas of the substrate, a decrease in insulation resistance was observed as the technological route was performed (after each subsequent operation, the resistance degraded). The degree of degradation can be reduced by reducing the duration of thermal operations. It has been shown that reducing the thickness of the masking oxide causes a decrease in insulation resistance. When using mesa-technology, it is possible to increase the insulation resistance by eliminating the high-temperature oxidation operation and, in fact, due to the absence of a masking coating during phosphorus deposition. Insulation by means of p+-type areas in the gaps between the active elements allows to obtain the highest insulation resistance values. The formation of these regions with a width of 100 μm in the gaps with a width of 200 μm allowed us to obtain an insulation resistance of 25-30 MΩ. To ensure the insulation of the active elements of photodiodes by this method, two thermal operations are added to the technological route. The number of thermal operations can be reduced by doping the entire silicon surface with a low boron concentration before forming a masking coating.

Low-temperature preparation of titanium dioxide thin layer for highly efficient CsPbI3 perovskite solar cells

All-inorganic CsPbI3 perovskite solar cells (PSCs) are the focus of the photovoltaic field due to their great thermal stability and potential in tandem devices. However, the common titanium dioxide (TiO2) electron transport layer (ETL) is manufactured at high temperature and is challenging to regulate the thickness. Here, we propose a unique strategy to fabricate thin TiO2 at low temperatures using atomic layer deposition (ALD) and a low-concentration Titanium tetrachloride/isopropanol (TiCl4/IPA) solution method. The ultra-thin compact ALD-TiO2 (A-TiO2) is employed to minimize the leakage channels and suppress the recombination rate at the tips of rough fluorine-doped tin oxide (FTO) substrates. Subsequently, the solution-TiO2 (S–TiO2) regulates the work function to improve the energy level alignment. The A-TiO2/S–TiO2 composite facilitates carrier charge extraction and transport at the interface between ETL and perovskite layer. As a result, the device-based A-TiO2/S–TiO2 ETL delivers a champion efficiency of 19.6% and outstanding stability under continuous illumination in ambient air. This study demonstrates a simple and cost-effective method for fabricating CsPbI3 PSC and promoting their potential for commercialization.

Squeeze cementing of micro-annuli: A visco-plastic invasion flow

Squeeze cementing is a process used to repair leaking oil and gas wells, in which a cement slurry is driven under pressure to fill an uneven leakage channel. This results in a Hele-Shaw type flow problem involving a yield stress fluid. We solve the flow problem using an augmented Lagrangian approach and advect forward the fluid concentrations until the flow stops. A planar invasion and a radial (perforation hole) invasion flow are studied. The characteristics of the flow penetration are linked to the channel thickness profile. The distribution of streamlines, flowing and non-flowing zones, evolves during the invasion flow. An interesting aspect of the results is the extreme variability in penetration metrics computed. These depend not only on the stochastic nature of the microannulus thickness, which has significant natural variation in both azimuthal and axial directions, but also on the “luck” of where the perforation hole is, relative to the larger/smaller microannulus gaps. This may explain the unreliability of the process.

Malignant currents: sodium leak channel NALCN propels prostate cancer aggressiveness.

Although ion transporters and channels have been extensively studied over the last couple of decades, there are still unresolved aspects with regards to their contribution to cancer cell biology. Recent work by Folcher etal (2023) reports a critical role for Na+ leak channel NALCN in metastatic prostate cancer. The study demonstrates that NALCN promotes metastatic spread to distant organs by controlling Ca2+ signaling.

Contributions of the Sodium Leak Channel NALCN to Pacemaking of Medial Ventral Tegmental Area and Substantia Nigra Dopaminergic Neurons.

We tested the role of the sodium leak channel, NALCN, in pacemaking of dopaminergic neuron (DAN) subpopulations from adult male and female mice. In situ hybridization revealed NALCN RNA in all DANs, with lower abundance in medial ventral tegmental area (VTA) relative to substantia nigra pars compacta (SNc). Despite lower relative abundance of NALCN, we found that acute pharmacological blockade of NALCN in medial VTA DANs slowed pacemaking by 49.08%. We also examined the electrophysiological properties of projection-defined VTA DAN subpopulations identified by retrograde labeling. Inhibition of NALCN reduced pacemaking in DANs projecting to medial nucleus accumbens (NAc) and others projecting to lateral NAc by 70.74% and 31.98%, respectively, suggesting that NALCN is a primary driver of pacemaking in VTA DANs. In SNc DANs, potentiating NALCN by lowering extracellular calcium concentration speeded pacemaking in wildtype but not NALCN conditional knockout mice, demonstrating functional presence of NALCN. In contrast to VTA DANs, however, pacemaking in SNc DANs was unaffected by inhibition of NALCN. Instead, we found that inhibition of NALCN increased the gain of frequency-current plots at firing frequencies slower than spontaneous firing. Similarly, inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) conductance increased gain but had little effect on pacemaking. Interestingly, simultaneous inhibition of NALCN and HCN resulted in significant reduction in pacemaker rate. Thus, we found NALCN makes substantial contributions to driving pacemaking in VTA DAN subpopulations. In SNc DANs, NALCN is not critical for pacemaking but inhibition of NALCN makes cells more sensitive to hyperpolarizing stimuli.SIGNIFICANCE STATEMENT Pacemaking in midbrain dopaminergic neurons (DAN) relies on multiple subthreshold conductances, including a sodium leak. Whether the sodium leak channel, NALCN, contributes to pacemaking in DANs located in the VTA and the SNc has not yet been determined. Using electrophysiology and pharmacology, we show that NALCN plays a prominent role in driving pacemaking in projection-defined VTA DAN subpopulations. By contrast, pacemaking in SNc neurons does not rely on NALCN. Instead, the presence of NALCN regulates the excitability of SNc DANs by reducing the gain of the neuron's response to inhibitory stimuli. Together, these findings will inform future efforts to obtain DAN subpopulation-specific treatments for use in neuropsychiatric disorders.