2,259 results match your criteria channel modulator

Agnostic sampling transceiver.

Opt Express 2021 May;29(10):14828-14840

Increasing demands for data centers, backbone, access, and wireless networks require inventive concepts to transmit and distribute digital or analog signal waveforms. We present a new, extremely simple transceiver concept, fundamentally different from conventional approaches. It does not rely on high-speed electronics and enables transmission of various time multiplexed analog waveforms or digital data signals with the maximum possible symbol rate in the same rectangular optical spectral band B. Read More

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Recurrent neural networks achieving MLSE performance for optical channel equalization.

Opt Express 2021 Apr;29(9):13033-13047

We explore recurrent and feedforward neural networks to mitigate severe inter-symbol interference (ISI) caused by bandlimited channels, such as high speed optical communications systems pushing the frequency response of transmitter components. We propose a novel deep bidirectional long short-term memory (BiLSTM) architecture that strongly emphasizes dependencies in data sequences. For the first time, we demonstrate via simulation that for QPSK transmission the deep BiLSTM achieves the optimal bit error rate performance of a maximum likelihood sequence estimator (MLSE) with perfect channel knowledge. Read More

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Allyl Isothiocyanate: A TAS2R38 Receptor-Dependent Immune Modulator at the Interface Between Personalized Medicine and Nutrition.

Front Immunol 2021 20;12:669005. Epub 2021 Apr 20.

Molecular Preventive Medicine, University Medical Center and Faculty of Medicine-University of Freiburg, Freiburg, Germany.

Understanding individual responses to nutrition and medicine is of growing interest and importance. There is evidence that differences in bitter taste receptor (TAS2R) genes which give rise to two frequent haplotypes, TAS2R38-PAV (functional) and TAS2R38-AVI (non-functional), may impact inter-individual differences in health status. We here analyzed the relevance of the TAS2R38 receptor in the regulation of the human immune response using the TAS2R38 agonist allyl isothiocyanate (AITC) from plants. Read More

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A Novel Modulator of STIM2-Dependent Store-Operated Ca2+ Channel Activity.

Acta Naturae 2021 Jan-Mar;13(1):140-146

Institute of Cytology of Russian Academy of Sciences, St. Petersburg, 194064 Russia.

Store-operated Ca entry is one of the main pathways of calcium influx into non-excitable cells, which entails the initiation of many intracellular processes. The endoplasmic reticulum Ca sensors STIM1 and STIM2 are the key components of store-operated Ca entry in mammalian cells. Under physiological conditions, STIM proteins are responsible for store-operated Ca entry activation. Read More

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Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes.

Sci Rep 2021 May 5;11(1):9621. Epub 2021 May 5.

Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada.

Glucocorticoids (GCs) are rapidly released in response to stress and play an important role in the physiological adjustments to re-establish homeostasis. The mode of action of GCs for stress coping is mediated largely by the steroid binding to the glucocorticoid receptor (GR), a ligand-bound transcription factor, and modulating the expression of target genes. However, GCs also exert rapid actions that are independent of transcriptional regulation by modulating second messenger signaling. Read More

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Patient personalized translational tools in Cystic fibrosis to transform data from bench to bed-side and back.

Am J Physiol Gastrointest Liver Physiol 2021 May 5. Epub 2021 May 5.

Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, United Statesgrid.239573.9.

Cystic fibrosis is a deadly multi-organ disorder caused by loss of function mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator (CFTR) chloride/bicarbonate ion channel. More than 1700 CFTR genetic variants exist that can cause CF, and, majority of these are extremely rare. Due to genetic and environmental influences, CF patients exhibit large phenotypic variation. Read More

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Characterization of Ca-Sensing Receptor-Mediated Ca Influx in Microvascular bEND.3 Endothelial Cells.

Chin J Physiol 2021 Mar-Apr;64(2):80-87

Department of Physiology, China Medical University, Taichung, Taiwan.

Ca-sensing receptors (CaSR), activated by elevated concentrations of extracellular Ca, have been known to regulate functions of thyroid cells, neurons, and endothelial cells (EC). In this report, we studied CaSR-mediated Ca influx in mouse cerebral microvascular EC (bEND.3 cells). Read More

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WIN55,212-2, a Dual Modulator of Cannabinoid Receptors and G Protein-Coupled Inward Rectifier Potassium Channels.

Biomedicines 2021 Apr 28;9(5). Epub 2021 Apr 28.

Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium.

The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. The present study established and validated the functional expression in a oocyte expression system of CB1 and CB2 receptors, interacting with heteromeric GIRK1/2 channels and a regulator of G protein signaling, RGS4. This ex vivo system enables the discovery of a wide range of ligands interacting orthosterically or allosterically with CB1 and/or CB2 receptors. Read More

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TRPM7-Mediated Calcium Transport in HAT-7 Ameloblasts.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Department of Oral Biology, Semmelweis University, H-1089 Budapest, Hungary.

TRPM7 plays an important role in cellular Ca, Zn and Mg homeostasis. TRPM7 channels are abundantly expressed in ameloblasts and, in the absence of TRPM7, dental enamel is hypomineralized. The potential role of TRPM7 channels in Ca transport during amelogenesis was investigated in the HAT-7 rat ameloblast cell line. Read More

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Repositioning Trimebutine Maleate as a Cancer Treatment Targeting Ovarian Cancer Stem Cells.

Cells 2021 Apr 16;10(4). Epub 2021 Apr 16.

New Drug Development Center, DGMIF, 80 Chumbok-ro, Dong-gu, Daegu 41061, Korea.

The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies targeting ovarian CSCs are needed to overcome the limitations of present treatments. Read More

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Spatial-Light-Modulator-Based Multichannel Data Transmission by Vortex Beams of Various Orders.

Sensors (Basel) 2021 Apr 24;21(9). Epub 2021 Apr 24.

Department of Technical Cybernetics, Samara National Research University, 443086 Samara, Russia.

We report an atmospheric multichannel data transmission system with channel separation by vortex beams of various orders, including half-integer values. For the demultiplexing of the communication channels, a multichannel diffractive optical element (DOE) is proposed, being matched with the used vortex beams. The considered approach may be realized without digital processing of the output images, but only based on the numbers of informative diffraction orders, similar to sorting. Read More

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Treatment of Pulmonary Disease of Cystic Fibrosis: A Comprehensive Review.

Antibiotics (Basel) 2021 Apr 23;10(5). Epub 2021 Apr 23.

Servicio de Neumología, Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain.

Cystic fibrosis (CF) is a genetic disease that causes absence or dysfunction of a protein named transmembrane conductance regulatory protein (CFTR) that works as an anion channel. As a result, the secretions of the organs where CFTR is expressed are very viscous, so their functionality is altered. The main cause of morbidity is due to the involvement of the respiratory system as a result of recurrent respiratory infections by different pathogens. Read More

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Phenotyping Rare CFTR Mutations Reveal Functional Expression Defects Restored by TRIKAFTA.

J Pers Med 2021 Apr 15;11(4). Epub 2021 Apr 15.

Programme in Molecular Medicine, Hospital for Sick Children, Toronto, ON M5G 8X4, Canada.

The rare Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations, c.1826A > G (H609R) and c.3067_3072delATAGTG (I1023_V1024del), are associated with severe lung disease. Read More

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Structural insights into the mechanisms and pharmacology of K potassium channels.

J Mol Biol 2021 Apr 19:166995. Epub 2021 Apr 19.

Cardiovascular Research Institute; Departments of Biochemistry and Biophysics, and Cellular and Molecular Pharmacology; California Institute for Quantitative Biomedical Research; Kavli Institute for Fundamental Neuroscience University of California, San Francisco, California 93858-2330 USA; Molecular Biophysics and Integrated Bio-imaging Division Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA. Electronic address:

Leak currents, defined as voltage and time independent flows of ions across cell membranes, are central to cellular electrical excitability control. The K (KCNK) potassium channel class comprises an ion channel family that produces potassium leak currents that oppose excitation and stabilize the resting membrane potential in cells in the brain, cardiovascular system, immune system, and sensory organs. Due to their widespread tissue distribution, Ks contribute to many physiological and pathophysiological processes including anesthesia, pain, arrythmias, ischemia, hypertension, migraine, intraocular pressure regulation, and lung injury responses. Read More

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Electrophysiological Approaches for the Study of Ion Channel Function.

Methods Mol Biol 2021 ;2302:49-67

Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Ion channels play crucial roles in cell physiology, and are a major class of targets for clinically relevant pharmaceuticals. Because they carry ionic current, the function and pharmacology of ion channels can be studied using electrophysiological approaches that range in resolution from the single molecule to many millions of molecules. This chapter describes electrophysiological approaches for the study of one representative ion channel that is defective in a genetic disease, and that is the target of so-called highly effective modulator therapies now used in the clinic: the cystic fibrosis transmembrane conductance regulator (CFTR). Read More

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January 2021

Emerging Role of PD-1 in the Central Nervous System and Brain Diseases.

Neurosci Bull 2021 Apr 20. Epub 2021 Apr 20.

Department of Anesthesiology, Duke University Medical Center, Durham, 27710, USA.

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer's disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. Read More

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The Involvement of Ca1.3 Channels in Prolonged Root Reflexes and Its Potential as a Therapeutic Target in Spinal Cord Injury.

Front Neural Circuits 2021 23;15:642111. Epub 2021 Mar 23.

Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

Spinal cord injury (SCI) results in not only the loss of voluntary muscle control, but also in the presence of involuntary movement or spasms. These spasms post-SCI involve hyperexcitability in the spinal motor system. Hyperactive motor commands post SCI result from enhanced excitatory postsynaptic potentials (EPSPs) and persistent inward currents in voltage-gated L-type calcium channels (LTCCs), which are reflected in evoked root reflexes with different timings. Read More

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Interferon Gamma-Mediated Oxidative Stress Induces Apoptosis, Neuroinflammation, Zinc Ion Influx, and TRPM2 Channel Activation in Neuronal Cell Line: Modulator Role of Curcumin.

Inflammation 2021 Apr 17. Epub 2021 Apr 17.

Departmant of Neuroscience, Institute of Health Sciences, Suleyman Demirel University, Isparta, Turkey.

Host defenses in the brain are modulated by the activation of several factors such as oxygen free radical species (ROS), Ca influx, and TRPM2 activation, and they are well-known adverse factors in neurotoxicity and neurodegenerative diseases. Importantly, recent data indicated a protective action of curcumin (CRC) via inhibition of TRPM2 on the inflammation factors, ROS, and apoptosis in hypoxia-induced SH-SY5Y neuronal cells. However, the relationship between interferon gamma (IFNg) exposure and TRPM2 activation in the SH-SY5Y cells are not fully identified. Read More

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On the molecular nature of large-pore channels.

J Mol Biol 2021 Apr 16:166994. Epub 2021 Apr 16.

W.M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address:

Membrane transport is a fundamental means to control basic cellular processes such as apoptosis, inflammation, and neurodegeneration and is mediated by a number of transporters, pumps, and channels. Accumulating evidence over the last half century has shown that a type of so-called "large-pore channel" exists in various tissues and organs in gap-junctional and non-gap-junctional forms in order to flow not only ions but also metabolites such as ATP. They are formed by a number of protein families with little or no evolutionary linkages including connexin, innexin, pannexin, leucine-rich repeat-containing 8 (LRRC8), and calcium homeostasis modulator (CALHM). Read More

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Airway Epithelial Inflammation Augments the Rescue of Mutant CFTR by Current CFTR Modulator Therapies.

Front Pharmacol 2021 30;12:628722. Epub 2021 Mar 30.

Marsico Lung Institute and Cystic Fibrosis Research Center, School of Medicine, University of North Carolina, Chapel Hill, NC, United States.

In cystic fibrosis (CF), defective biogenesis and activity of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to airway dehydration and impaired mucociliary clearance, resulting in chronic airway infection and inflammation. The most common CFTR mutation, F508del, results in a processing defect in which the protein is retained in the endoplasmic reticulum and does not reach the apical surface. CFTR corrector compounds address this processing defect to promote mutant CFTR transfer to the apical membrane. Read More

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The K7 Modulator, Retigabine, is an Efficacious Antiseizure Drug for Delayed Treatment of Organophosphate-induced Status Epilepticus.

Neuroscience 2021 May 6;463:143-158. Epub 2021 Apr 6.

United States Army Medical Research Institute of Chemical Defense, Medical Toxicology Research Division, Neuroscience Department, 2900 Ricketts Point Rd, Aberdeen Proving Ground, MD 21010, USA.

Benzodiazepines are the primary treatment option for organophosphate (OP)-induced status epilepticus (SE), but these antiseizure drugs (ASDs) lose efficacy as treatment is delayed. In the event of a mass civilian or military exposure, significant treatment delays are likely. New ASDs that combat benzodiazepine-resistant, OP-induced SE are critically needed, particularly if they can be efficacious after a long treatment delay. Read More

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Improved Control of Tyrosine Kinase Inhibitor-Induced Diarrhea with a Novel Chloride Channel Modulator: A Case Report.

Oncol Ther 2021 Apr 7. Epub 2021 Apr 7.

Division of Hematology and Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.

Despite the efficacy of tyrosine kinase inhibitors (TKIs) across multiple cancers, side effects including treatment-related diarrhea can impede a patient's ability to reach therapeutic doses or stay on therapy. Below, we present the case of a 72-year-old patient with metastatic papillary renal cell carcinoma recurrent despite nephrectomy. Over the course of treatment, the patient received multiple different tyrosine kinase inhibitors with varying efficacy. Read More

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Discovery of CFTR modulators for the treatment of cystic fibrosis.

Expert Opin Drug Discov 2021 Apr 13:1-17. Epub 2021 Apr 13.

Department of Physiology, McGill University, Montréal, Canada.

Introduction: Cystic fibrosis (CF) is a life-threatening inherited disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein, an anion channel expressed at the apical membrane of secretory epithelia. CF leads to multiorgan dysfunction with progressive deterioration of lung function being the major cause of untimely death. Conventional CF therapies target only symptoms and consequences downstream of the primary genetic defect and the current life expectancy and quality of life of these individuals are still very limited. Read More

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Direct phase modulation via optical injection: theoretical study.

Opt Express 2021 Mar;29(6):9574-9588

Direct phase modulation via optical injection is a newly developed method for coding the phase of a gain-switched laser, which meets high requirements placed on transmitters for quantum key distribution: compactness, low losses, compatibility with CMOS technologies, and the absence of undesirable effects leading to the side-channel information leakage. Despite the successful implementation and good prospects for the further development of this system, there is still a lack of theoretical investigations of this scheme in the literature. Here, for the first time, we perform its theoretical analysis. Read More

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Posttranslational regulation of CALHM1/3 channel: N-linked glycosylation and S-palmitoylation.

FASEB J 2021 May;35(5):e21527

Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Among calcium homeostasis modulator (CALHM) family members, CALHM1 and 3 together form a voltage-gated large-pore ion channel called CALHM1/3. CALHM1/3 plays an essential role in taste perception by mediating neurotransmitter release at channel synapses of taste bud cells. However, it is poorly understood how CALHM1/3 is regulated. Read More

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A Phase 2 Proof-of-Concept, Randomized, Placebo-Controlled Trial of CX-8998 in Essential Tremor.

Mov Disord 2021 Mar 25. Epub 2021 Mar 25.

vZenium, LLC, Arlington, Massachusetts, USA.

Background: Available essential tremor (ET) therapies have limitations.

Objectives: The objective of this study was to evaluate CX-8998, a selective T-type calcium channel modulator, in essential tremor.

Methods: Patients 18-75 years old with moderate to severe essential tremor were randomized 1:1 to receive CX-8998 (titrated to 10 mg twice daily) or placebo. Read More

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Efficient all-optical modulator based on a periodic dielectric atomic lattice.

Opt Express 2021 Jan;29(2):2712-2719

All-optical devices used to process optical signals without electro-optical conversion plays a vital role in the next generation of optical information processing systems. We demonstrate an efficient all-optical modulator that utilizes a periodic dielectric atomic lattice produced in a gas of Rb vapor. Four orders of diffraction patterns are observed when a probe laser is passed through the lattice. Read More

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January 2021

16-channel tunable and 25-Gb/s EAM-integrated DBR-LD for WDM-based mobile front-haul networks.

Opt Express 2021 Jan;29(2):1805-1812

We report a tunable distributed Bragg reflector-laser diode (DBR-LD) integrated with an electro-absorption-modulator (EAM) at an operating wavelength of 1.3 µm. This LD consists of gain, phase control (PC), DBR, and EAM sections, realized by using a butt-coupling technique in monolithically integrating the multiple quantum wells (MQWs) with the passive core and by applying an etched-mesa buried hetero-structure (EMBH) to the resonance cavity (i. Read More

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January 2021

81-beam coherent combination using a programmable array generator.

Opt Express 2021 Feb;29(4):5407-5418

We have generated 81 independently controllable beams using a spatial light modulator and combined them on a diffractive combiner, to characterize the combiner and develop a fast phase error detection scheme. A key parameter of the diffractive combiner is measured in a new way, enabling an efficient combination when programming calibrated phases of each beam. This testbed provides a platform for development of advanced feedback phase control of high channel-count beam combination. Read More

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February 2021

STIM1 Regulates Endothelial Calcium Overload and Cytokine Upregulation During Sepsis.

J Surg Res 2021 Mar 10;263:236-244. Epub 2021 Mar 10.

Department of Emergency, The First Medical Center, Chinese PLA(People's Liberation Army) General Hospital, Beijing, China. Electronic address:

Background: Stromal interaction molecule 1 (STIM1)-mediated store-operated Ca entry (SOCE) is now recognized as the main mechanism of the majority of nonexcitable cell calcium influx. Calcium overload is a primary mechanism of endothelial cell injury during systemic inflammatory response and sepsis. Whether STIM1-mediated SOCE plays a role in calcium overload in vascular endothelial cell injury remains unclear. Read More

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