Direct Switching Research Articles

Screening of lactate dehydrogenase inhibitor from bioactive compounds in natural products by electrophoretically mediated microanalysis

Lactate dehydrogenase (LDH) is a key enzyme in the glycolysis, which has been reported that the expression of LDH is elevated in a variety of cancer types and can promote tumor invasion and metastasis. Therefore, LDH has come to be an emerging therapeutic target for cancer. In this work, we described a new strategy for rapid screening of LDH inhibitors from natural products by integrating electrophoretically mediated microanalysis (EMMA), transverse diffusion of laminar flow profiles (TDLFP) and rapid pressure direction switching. LDH activity could be assayed by the quantification of the peak area of the produced β-Nicotinamide adenine dinucleotide hydrate (NAD+) and the inhibitory effect on LDH was reflected by the reduction of NAD+ peak area. Parameters affecting CE separation and enzymatic reaction were evaluated, including the pH of background electrolyte, incubation time, methanol percentage and enzyme concentration. The Michaelis-Menten constant (Km) determined on-line by EMMA method were 226.9 μM and 31.8 μM for substrates sodium pyruvate and NADH, respectively and the half-maximal inhibitory concentration (IC50) for the known positive inhibitor gossypol was determined to be 9.269 μM, which was comparable with the previous literature. Then the inhibitory activity of 12 bioactive compounds from natural products on LDH was investigated by employing the developed method. Three compounds including quercetin, luteolin, ursolic acid had potential inhibitory effect on LDH. Molecular docking study was implemented and well supported the experimental results. This study provides a potential tool for the preliminary screening of LDH inhibitors from bioactive compounds in natural products by capillary electrophoresis.

Efficacy of Brivaracetam in children with epilepsy

Background and objectivesTo determine the efficacy, tolerance, and safety of BRV in children with epilepsy. MethodsA retrospective study of patients with epilepsy who received treatment with BRV before age 16 years and underwent a minimum follow-up of 3 months. Method and resultsSixty-six patients were included in the study. Patients received BRV at a mean age of 8.8 years (range 1−16 years). The majority (93.4 %) had refractory epilepsy, 27 with epileptic encephalopathy. The median maximum dose used was 4.3 mg/kg/day. In 30.3 % of the cases, seizure frequency was reduced by over 50 %, and 9 % remained seizure-free. Greater efficacy was observed in those patients who received higher doses and when a direct switch from levetiracetam (LEV) to BRV was performed. The ineffectiveness of LEV was not related to a failure to respond to BRV treatment. Side effects were identified in 24.2 % of the cases, the most frequent being irritability and drowsiness. ConclusionsBRV appears to be an effective, safe, and well-tolerated AED in children with refractory epilepsy.

Coordinating directional switches in pigeon flocks: the role of nonlinear interactions

The mechanisms inducing unpredictably directional switches in collective and moving biological entities are largely unclear. Deeply understanding such mechanisms is beneficial to delicate design of biologically inspired devices with particular functions. Here, articulating a framework that integrates data-driven, analytical and numerical methods, we investigate the underlying mechanism governing the coordinated rotational flight of pigeon flocks with unpredictably directional switches. Particularly using the sparse Bayesian learning method, we extract the inter-agent interactional dynamics from the high-resolution GPS data of three pigeon flocks, which reveals that the decision-making process in rotational switching flight performs in a more nonlinear manner than in smooth coordinated flight. To elaborate the principle of this nonlinearity of interactions, we establish a data-driven particle model with two potential wells and estimate the mean switching time of rotational direction. Our model with its analytical and numerical results renders the directional switches of moving biological groups more interpretable and predictable. Actually, an appropriate combination of natures, including high density, stronger nonlinearity in interactions, and moderate strength of noise, can enhance such highly ordered, less frequent switches.

PD11-09 CELLULAR MECHANISMS OF 5-ALPHA REDUCTASE INHIBITOR TREATMENT RESISTANCE IN BENIGN PROSTATIC HYPERPLASIA

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-09 CELLULAR MECHANISMS OF 5-ALPHA REDUCTASE INHIBITOR TREATMENT RESISTANCE IN BENIGN PROSTATIC HYPERPLASIA Diya Binoy Joseph, Gervaise Henry, Alicia Malewska, Jeffrey Reese, Ryan Mauck, Jeffrey Gahan, Ryan Hutchinson, James Mohler, Claus Roehrborn, and Douglas Strand Diya Binoy JosephDiya Binoy Joseph More articles by this author , Gervaise HenryGervaise Henry More articles by this author , Alicia MalewskaAlicia Malewska More articles by this author , Jeffrey ReeseJeffrey Reese More articles by this author , Ryan MauckRyan Mauck More articles by this author , Jeffrey GahanJeffrey Gahan More articles by this author , Ryan HutchinsonRyan Hutchinson More articles by this author , James MohlerJames Mohler More articles by this author , Claus RoehrbornClaus Roehrborn More articles by this author , and Douglas StrandDouglas Strand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001986.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 5-alpha reductase inhibitors (5ARIs) are prescribed to reduce prostate volume and alleviate lower urinary tract symptoms due to Benign Prostatic Hyperplasia (BPH). In some patients, prostate shrinkage is focal and does not result in improved urinary symptoms. We examined the phenotypic changes in glandular acini accompanying 5ARI treatment to determine the cellular mechanisms of treatment resistance. METHODS: Mass spectrometry was performed to measure 5ARI drug and hormone levels in prostate tissue from BPH patients. Patients with confirmed presence of 5ARI drug, low DHT and histological response were selected for spatial transcriptomics. Visium spatial transcriptomics was performed on histologically-responsive and non-responsive regions. Primary prostate epithelial cells were treated with TNF-α to activate NF-κB and qPCR was used to measure lineage-specific gene expression. RESULTS: We observed that patients with detectable levels of 5ARI drug display reduced DHT and increased testosterone regardless of phenotypic response. In 5ARI treated patients, regions of normal prostate glandular architecture can often be seen adjacent to regions of smaller acini with multiple cell layers, defined as histologically-resistant and -responsive, respectively. Spatial transcriptomics performed on histologically-resistant vs. -responsive regions revealed a urethral club-like molecular signature in small acini. These regions displayed increased TNF-α expression and nuclear localization and phosphorylation of p65. Treatment of primary prostate epithelial cells with TNF-α activated NF-κB and upregulated club cell genes, recapitulating the in vivo expression of these genes in responsive regions. CONCLUSIONS: We conclude that 5ARI treatment results in small ducts of androgen-independent club cells. It is unclear whether 5ARI treatment is inducing direct lineage switching of prostate luminal cells to club-like cells for survival or whether 5ARI-induced apoptosis of prostate luminal cells is indirectly driving altered differentiation of basal epithelia to club epithelia. Alternatively, androgen-independent club cells may be expanded during BPH and survive 5ARI treatment and repopulate prostate glands after 5ARI withdrawal. Further studies are required to determine how adjacent, histologically normal prostate glands maintain AR-dependent signaling despite low levels of tissue DHT and whether club cells can act as progenitors during androgen replenishment and prostate regrowth. Source of Funding: AUA Research Scholar Award 659333 to DBJ, R01 DK115477 to DWS and NCI P30CA016056 to Roswell Park Comprehensive Cancer Center for support of the Bioanalytical, Metabolomics, and Pharmacokinetics Shared Resource © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e201-e201 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diya Binoy Joseph More articles by this author Gervaise Henry More articles by this author Alicia Malewska More articles by this author Jeffrey Reese More articles by this author Ryan Mauck More articles by this author Jeffrey Gahan More articles by this author Ryan Hutchinson More articles by this author James Mohler More articles by this author Claus Roehrborn More articles by this author Douglas Strand More articles by this author Expand All Advertisement Loading ...

Imperfect symmetry of real annular combustors: beating thermoacoustic modes and heteroclinic orbits

In jet engines and gas turbines, the annular shape of the combustion chamber allows the appearance of self-oscillating azimuthal thermoacoustic modes. We report experimental evidence of a new type of modal dynamics characterised by periodic switching of the spinning direction and develop a theoretical model that fully reproduces this phenomenon and explains the underlying mechanisms. It is shown that tiny asymmetries of the geometry, the mean temperature field, the thermoacoustic response of the flames or the acoustic impedance of the walls, present in any real systems, can induce these heteroclinic orbits. The model also explains experimental observations showing a statistically dominant spinning direction despite the absence of swirling flow, or pairs of preferred nodal line directions.

L-Histidine-Derived Smart Antifouling Biohybrid with Multistimuli Responsivity.

A novel dual pH/thermoresponsive amphiphilic poly(histidine methacrylamide)-block-hydroxyl-terminated polybutadiene-block-poly(histidine methacrylamide) (PHisMAM-b-PB-b-PHisMAM) triblock copolymer biohybrid, composed of hydrophobic PB and ampholytic PHisMAM segments, is developed via direct switching from living anionic polymerization to recyclable nanoparticle catalyst-mediated reversible-deactivation radical polymerization (RDRP). The transformation involved in situ postpolymerization modification of living polybutadiene-based carbanionic species, end-capped with ethylene oxide, into dihydroxyl-terminated polybutadiene and a subsequent reaction with 2-bromo-2-methylpropionyl bromide resulting in a telechelic ATRP macroinitiator (Br-PB-Br). Br-PB-Br was used to mediate RDRP of an l-histidine-derived monomer, HisMAM, yielding a series of PHisMAM-b-PB-b-PHisMAM triblock copolymers. The copolymer's stimuli response was assessed against pH and temperature changes. The copolymer is capable of switching among its zwitterionic, anionic, and cationic forms and exhibited unique antifouling properties in its zwitterionic form. These novel triblock copolymers are expected to be show promising potential in biomedical applications.

Ultralow-VπL Silicon Electro-Optic Directional Coupler Switch With a Liquid Crystal Cladding

An ultralow-V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">π</sub> L photonic switch device is demonstrated utilizing the high optical and electrical field confinement in silicon slot waveguides coupled with the strong electro-optic response of nematic liquid crystals. A silicon photonic directional coupler switch with a modulation efficiency of 0.0195 V·mm and a loss-efficiency product of 0.0624 V·dB is achieved. The 1.5 mm long device is based on two-mode interference within a single slot waveguide resulting in a V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">π</sub> of 0.013 V and an extinction ratio of ~ 9dB at 1550 nm wavelength. The power consumption of the photonic switch is estimated to be below 0.6 nW and it possesses a response time of <; 1.5 ms. A comparative performance study between the directional coupler switch and a Mach-Zehnder Interferometer (MZI) switch is performed. The directional coupler switch is projected to have a smaller footprint and lower optical loss compared to a similar design MZI switch making it a strong candidate for switch matrix designs and applications.

Modeling spatiotemporally varying protein-protein interactions in CyLaKS, the Cytoskeleton Lattice-based Kinetic Simulator.

Interaction of cytoskeletal filaments, motor proteins, and crosslinking proteins drives important cellular processes such as cell division and cell movement. Cytoskeletal networks also exhibit nonequilibrium self-assembly in reconstituted systems. An emerging problem in cytoskeletal modeling and simulation is spatiotemporal alteration of the dynamics of filaments, motors, and associated proteins. This can occur due to motor crowding, obstacles along the filament, motor interactions and direction switching, and changes, defects, or heterogeneity in the filament binding lattice. How such spatiotemporally varying cytoskeletal filaments and motor interactions affect their collective properties is not fully understood. We developed the Cytoskeleton Lattice-based Kinetic Simulator (CyLaKS) to investigate such problems. The simulation model builds on previous work by incorporating motor mechanochemistry into a simulation with many interacting motors and/or associated proteins on a discretized lattice. CyLaKS also includes detailed balance in binding kinetics, movement, and lattice heterogeneity. The simulation framework is flexible and extensible for future modeling work and is available on GitHub for others to freely use or build upon. Here we illustrate the use of CyLaKS to study long-range motor interactions, microtubule lattice heterogeneity, motion of a heterodimeric motor, and how changing crosslinker number affects filament separation.

A molecular communication channel consisting of a single reversible chain of hydrogen bonds in a conformationally flexible oligomer

SummaryCommunication of information through the global switching of conformation in synthetic molecules has hitherto entailed the inversion of chirality. Here, we report a class of oligomer through which information may be communicated through a global reversal of polarity. Ethylene-bridged oligoureas are constitutionally symmetrical, conformationally flexible molecules organized by a single chain of hydrogen bonds running the full length of the oligomer. NMR reveals that this hydrogen-bonded chain may undergo a coherent reversal of directionality. The directional uniformity of the hydrogen-bond chain allows it to act as a channel for the spatial communication of information on a molecular scale. A binding site at the terminus of an oligomer detects local information about changes in pH or anion concentration and transmits that information—in the form of a directionality switch in the hydrogen-bond chain—to a remote polarity-sensitive fluorophore. This propagation of polarity-encoded information provides a new mechanism for molecular communication.

Deacetylation as a receptor-regulated direct activation switch for pannexin channels

Activation of Pannexin 1 (PANX1) ion channels causes release of intercellular signaling molecules in a variety of (patho)physiological contexts. PANX1 can be activated by G protein-coupled receptors (GPCRs), including α1-adrenergic receptors (α1-ARs), but how receptor engagement leads to channel opening remains unclear. Here, we show that GPCR-mediated PANX1 activation can occur via channel deacetylation. We find that α1-AR-mediated activation of PANX1 channels requires Gαq but is independent of phospholipase C or intracellular calcium. Instead, α1-AR-mediated PANX1 activation involves RhoA, mammalian diaphanous (mDia)-related formin, and a cytosolic lysine deacetylase activated by mDia – histone deacetylase 6. HDAC6 associates with PANX1 and activates PANX1 channels, even in excised membrane patches, suggesting direct deacetylation of PANX1. Substitution of basally-acetylated intracellular lysine residues identified on PANX1 by mass spectrometry either prevents HDAC6-mediated activation (K140/409Q) or renders the channels constitutively active (K140R). These data define a non-canonical RhoA-mDia-HDAC6 signaling pathway for GαqPCR activation of PANX1 channels and uncover lysine acetylation-deacetylation as an ion channel silencing-activation mechanism.

Direct switching of polarization vortex in triangular ferroelectric nanodots: Role of crystal orientation

Attaining an energy-efficient pathway to switch the rotation of polarization vortex with the use of trivial homogeneous electric field is essentially important for low-power consumption electronic nanodevices, yet still challenging. In this study, we systematically investigate the switching behaviors of polarization vortex in triangular ferroelectric nanodots with different crystal orientations. The obtained results exhibit diversity pathways for the vortex switching, including both indirect and direct switching, which depend on the crystal orientation. In the indirect pathway, the switching process requires a destruction of initial vortex domain structure to form a rectilinear domain at a large electric field. Otherwise, in the direct switching pathway, the initial vortex is switched to an opposite one without the stabilization of an intermediate state. Importantly, the direct pathway requires a lower switching field compared to that in the indirect ones. We further elucidate the temporal evolution of domain structure during the direct switching of polarization vortex in the triangular nanodot. A comprehensive viewpoint on the effect of crystal orientation is expressed, from which the advantages of direct switching are clarified. The present study suggests an efficient route on the practical control of vortex rotation in ferroelectric nanostructures under homogeneous electric field.

Magnetic field modulated photoelectric devices in ferromagnetic semiconductor CrXh (X = S/Se, h = Cl/Br/I) van der Waals heterojunctions

The interactive control between electron charge and spin is essential to spintronics. Two-dimensional (2D) ferromagnetic semiconductors (FMSs) are a kind of unique candidate materials that could lead to flexible magnetoelectric and magneto-optic applications. In this Letter, we construct a series of van der Waals heterostructures by 2D magnetic CrXh (X = S/Se, h = Cl/Br/I) monolayers. Based on first-principles calculations, both monolayers and heterostructures have been demonstrated as intrinsic FMSs with large magnetic moments, suitable bandgaps, good carrier mobility, and high Curie temperatures. Taking advantage of the heterojunction effect, one can precisely control the charge transport behavior by forming three types of band alignments. Under an external alternating magnetic field, CrSeBr/CrSeCl and CrSBr/CrSI heterostructures can reversibly reconfigure between type-II and type-I band alignments upon switching of the spin direction. Combining the robust magnetic ordering and distinctive spin-polarized band alignment, our designed CrXh based magnetic heterostructures are ideal candidates for innovative magnetic-field-modulated photoelectric devices for realizing ultrarapid and reversible “write-read” processes.

Direct and two-step single anastomosis duodenal switch (SADI-S): Unicentric comparative analysis of 232 cases

IntroductionThe “Single Anastomosis Duodeno-Ileal bypass with Sleeve gastrectomy” (SADI-S) is a bariatric surgery conceived to simplify the duodenal switch in order to reduce its postoperative complications. The objective of this study is to assess the safety and efficacy of SADI-S, comparing its results in both direct and two-step procedure. MethodsUnicentric cohort study that includes patients submitted to SADI-S, both direct or in two-step, between 2014 and 2019. ResultsTwo hundred thirty-two patients were included, 192 were submitted to direct SADI-S and 40 had previously undergone a sleeve gastrectomy. The severe complications rate (Clavien-Dindo ≥ IIIA) was 7.8%, being hemoperitoneum and duodenal stump leak the most frequent ones. One patient was exitus between the first 90 days after surgery (0.4%). Patients submitted to direct SADI-S had an initial body mass index (BMI) of 49.6 kg/m2 in comparison of 56.2 kg/m2 in the two-step SADI-S (P < .001). The mean excess weight loss (EWL) at two years was higher in direct SADI-S (77.3 vs. 59.3%, P < .05). Rate of comorbidities resolution was 88.5% for diabetes, 73.0% for hypertension, 77.0% for dyslipidemia and 85.7% for sleep apnea, with no differences between both techniques. ConclusionIn medium term, SADI-S is a safe and effective technique that offers a satisfactory weight loss and remission of comorbidities. Patients submitted to two-step SADI-S had a higher initial BMI and presented a lower EWL than direct SADI-S.

A Real-World Analysis of Treatment Patterns and Clinical Characteristics Among Patients with COPD Who Initiated Multiple-Inhaler Triple Therapy in New Zealand.

PurposeReal-world data on maintenance treatment and prescription patterns provide insights into healthcare management among patients with chronic obstructive pulmonary disease (COPD), which benefits our understanding of current COPD treatment patterns in New Zealand.MethodsWe retrospectively analyzed real-world data from the HealthStat general practice database to evaluate treatment patterns among patients with COPD in New Zealand who initiated multiple-inhaler triple therapy (MITT): inhaled corticosteroid (ICS) + long-acting muscarinic antagonist + long-acting β2-agonist (LABA). Our main objective described treatment patterns (class, duration, modification, persistence, and adherence) and characteristics of patients with COPD initiating MITT between 1 May 2016 and 30 April 2017, with 12-months’ follow-up. We also assessed the number of patients receiving MITT between 2015 and 2017, among a larger patient population receiving long-acting bronchodilator and ICS-containing therapies.ResultsOf 6249 eligible patients, 421 (mean age 67.3 years; mean number exacerbations at baseline 1.8) initiated MITT: 59.1% received combination ICS/LABA therapy prior to MITT initiation, and median treatment duration prior to MITT initiation was 350 days. Overall, 33.5% of patients remained on index treatment for 12 months. Of the remaining patients who modified treatment (on average at 144.4 days), those who had a direct switch (24.9%) or retreatment (13.5%) remained on MITT, 19.7% of patients stepped down to mono/dual therapy, and 8.3% discontinued treatment. Mean (standard deviation) persistence to any MITT over 12 months was 47.3 (50.0), and 53.4% of patients were considered adherent to MITT. Total proportions of patients receiving long-acting bronchodilator therapy and MITT increased between 2015 and 2017.ConclusionMost patients with COPD in New Zealand who initiated MITT had characteristics appropriate for triple therapy prescription, suggesting prescription behavior among general practitioners was largely consistent with treatment guidelines. Our findings may help optimize treatment decisions, with a focus on improving long-term triple therapy persistence and adherence.

Electrically controllable active plasmonic directional coupler of terahertz signal based on a periodical dual grating gate graphene structure

We propose a concept of an electrically controllable plasmonic directional coupler of terahertz signal based on a periodical structure with an active (with inversion of the population of free charge carriers) graphene with a dual grating gate and numerically calculate its characteristics. Proposed concept of plasmon excitation by using the grating gate offers highly effective coupling of incident electromagnetic wave to plasmons as compared with the excitation of plasmons by a single diffraction element. The coefficient which characterizes the efficiency of transformation of the electromagnetic wave into the propagating plasmon has been calculated. This transformation coefficient substantially exceeds the unity (exceeding 6 in value) due to amplification of plasmons in the studied structure by using pumped active graphene. We have shown that applying different dc voltages to different subgratings of the dual grating gate allows for exciting the surface plasmon in graphene, which can propagate along or opposite the direction of the structure periodicity, or can be a standing plasma wave for the same frequency of the incident terahertz wave. The coefficient of unidirectionality, which is the ratio of the plasmon power flux propagating along (opposite) the direction of the structure periodicity to the sum of the absolute values of plasmon power fluxes propagating in both directions, could reach up to 80 percent. Two different methods of the plasmon propagation direction switching are studied and possible application of the found effects are suggested.

Numerical investigation on Ge2Sb2Te5-assisted reconfigurable asymmetric directional coupler-based switches

The performance analysis on phase change material germanium-antimony-tellurium-Ge2Sb2Te5 (GST)-assisted silicon waveguide-based non-volatile 1 × 2 and 2 × 2 switches are proposed. The designed structure contains a hybrid silicon waveguide and a regular silicon waveguide. By perfectly choosing the design considerations of the proposed switches, the power of transverse electric mode is coupled and shifted to cross port as an output at the amorphous state of GST (aGST), and for the crystalline state of GST (cGST), the input mode passes through the bar port as an output. The performances of the switches are evaluated by numerical calculations with the help of mode analysis of 2D finite-element method (FEM), and it is further verified by 3D finite-difference time-domain method (FDTD). For the 1 × 2 and 2 × 2 proposed switches, the obtained insertion loss (IL) of both phases of GST is <1 dB. For 1 × 2 switch design, the calculated cross-talk (CT) and extinction ratio (ER) are −31.32 and 31.31 dB, respectively at aGST state and for the cGST state, the values of CT and ER are −20.77 and 20.73 dB at 1550-nm operating wavelength. Similarly, for 2 × 2 switch design, the observed CT and ER are −32.7 and 32.69 dB, correspondingly at aGST state and for the cGST state; they are −11.98 and 11.71 dB, respectively. An additional optimization is realized via variations in the wavelength, GST width, and the coupling gap with the help of FEM analysis. Hence, broadband (80 nm) and ultracompact (∼20 μm) switches are proposed with low IL, high ER, and low CT, which can be suitable for reconfigurable optical interconnects, optical field-programmable gate array applications, microwave photonics, and quantum computing.

MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity

Neuron-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), direct cell fate switching of human fibroblasts to neurons when ectopically expressed by repressing antineurogenic genes. How these miRNAs function after the repression of fibroblast genes for neuronal fate remains unclear. Here, we identified targets of miR-9/9*-124 as reprogramming cells activate the neuronal program and reveal the role of miR-124 that directly promotes the expression of its target genes associated with neuronal development and function. The mode of miR-124 as a positive regulator is determined by the binding of both AGO and a neuron-enriched RNA-binding protein, ELAVL3, to target transcripts. Although existing literature indicates that miRNA-ELAVL family protein interaction can result in either target gene up-regulation or down-regulation in a context-dependent manner, we specifically identified neuronal ELAVL3 as the driver for miR-124 target gene up-regulation in neurons. In primary human neurons, repressing miR-124 and ELAVL3 led to the down-regulation of genes involved in neuronal function and process outgrowth and cellular phenotypes of reduced inward currents and neurite outgrowth. Our results highlight the synergistic role between miR-124 and RNA-binding proteins to promote target gene regulation and neuronal function.

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.

A bi-bandwidth extended state observer for a system with measurement noise and its application to aircraft with abrupt structural damage

In this paper, we address the problem of disturbance estimation for a class of linear systems with both fast time-varying uncertainty and measurement noise. A novel bi-bandwidth extended state observer (BESO) is proposed to achieve fast disturbance tracking and satisfactory noise suppression. The direction information of the estimation errors is used through a directional switching operator (DSO) to dynamically tune the bandwidth of the BESO. Sufficient conditions for the stability of the BESO are given, and the error dynamics are proven to be bounded and to converge in finite time. A comprehensive comparison of the BESO and three other representative approaches is presented, which shows that the BESO achieves a performance improvement of greater than 13%. A closed-loop control application for a structurally damaged aircraft is also provided to demonstrate the effectiveness and efficiency of the BESO.

Constricted Apertures for Dynamic Trapping and Micro-/Nanoscale Discrimination Based on Recapture Kinetics.

Sensing via analyte passage through a constricted aperture is a powerful and robust technology which is being utilized broadly, from DNA sequencing to single virus and cell characterization. Micro- and nanoscale structures typically translocate a constricted aperture, or pore, using electrophoretic force. In the present work, we explore the advances in metrology which can be achieved through rapid directional switching of hydrodynamic forces. Interestingly, multipass measurements of microscale and nanoscale structures achieve cell discrimination. We explore this cell-discrimination phenomenon as well as other features of hydrodynamic focusing such as dynamic trapping and discrete interval sensing.