channels

SEMICONDUCTOR DEVICE INCLUDING NANOWIRE TRANSISTORS WITH HYBRID CHANNELS

A semiconductor device is provided that includes an n-type field effect transistor including a plurality of vertically stacked silicon-containing nanowires located in one region of a semiconductor substrate, and a p-type field effect transistor including a plurality of vertically stacked silicon germanium alloy nanowires located in another region of a semiconductor substrate. Each vertically stacked silicon-containing nanowire of the n-type field effect transistor has a different shape than the shape of each vertically stacked silicon germanium alloy nanowire of the p-type field effect transistor.




channels

Supervision of Input Signal Channels

The present disclosure pertains to systems and methods for monitoring a plurality of analog-to-digital converters. In one embodiment, a plurality of input channels may each be in communication with a different phase of a three-phase electric power delivery system. The input channels may be configured to receive analog signals from the different phases. A composite signal subsystem may be configured to generate a composite signal based on the plurality of input channels. An analog-to-digital converter subsystem may be configured to produce a digitized representation of each of the plurality of input channels and a digitized representation of the composite signal. An analog-to-digital converter monitor subsystem may identify an error in the analog-to-digital conversion based on the digitized representation of the composite signal and the digitized representations of the plurality of input channels.




channels

OPERATION OF DIAGNOSTIC DEVICES INVOLVING MICROCHANNELS AND ELECTRODES

An assembly is provided for interfacing with a microfluidic chip having at least one microscopic channel configured to receive a liquid sample for analysis. The assembly includes a chip carrier, an electronics module, an optical module, and a mechanical module. The chip carrier includes a base and a cover defining a cavity to receive the microfluidic chip. The electronics module includes a signal generator which applies at least one electrokinetic signal electrode(s) of the chip. The optical module includes an excitation radiation source which causes excitation radiation to impinge on the sample, and an emission radiation detector which detects radiation emitted from the sample. The mechanical module includes a chip-carrier receiving structure, relatable with respect to the optical module for focus and at least one degree of translational freedom.




channels

TANGENTIAL FILTER WITH A SUPPORTING ELEMENT INCLUDING A SET OF CHANNELS

A tangential filter for filtration of a fluid includes a support element, wherein, along a transverse plane perpendicular to the central axis of the support element a) the support element includes in its central portion only inner channels that do not share a common wall with its outer surface, the inner channels having a substantially equivalent hydraulic diameter, b) the support element includes peripheral channels, including at least first and second adjacent peripheral channels, each of the two channels sharing a common wall with the outer surface, c) the ratio of the hydraulic diameter of the first channel to the hydraulic diameter of the second channel is greater than or equal to 1.1, d) the number of peripheral first channels is greater than or equal to the number of peripheral second channels, e) the second channel has a hydraulic diameter substantially identical to the hydraulic diameter of the inner channels.




channels

COOLING OF ELECTRONICS USING FOLDED FOIL MICROCHANNELS

Embodiments are generally directed to cooling of electronics using folded foil microchannels. An embodiment of an apparatus includes a semiconductor die; a substrate, the semiconductor die being coupled with the substrate; and a cooling apparatus for the semiconductor die, wherein the cooling apparatus includes a folded foil preform, the folded foil forming a plurality of microchannels, and a fluid coolant system to direct a fluid coolant through the microchannels of the folded foil.




channels

Market dynamics are different for all channels; e-commerce ecosystem will stabilise: Tupperware MD Deepak Chhabra

Tupperware India's managing director Deepak Chhabra talks about how integrating the direct sales force with the retail franchisee model is working for the home and kitchen-ware maker.




channels

Routing Maschine Channels to the SSL Mixer in Reason 11

Still checking out the Reason 11 demo and wanted to make a quick video showing how to route channels from Maschine out to the SSL mixer in Reason. This gives you more control over individual pads or groups when creating a mixing.

The post Routing Maschine Channels to the SSL Mixer in Reason 11 appeared first on Maschine Tutorials.



  • DAW & Host Integration
  • Free Maschine Tutorials

channels

I need to watch 9 different channels.

I need 9 TV tuners so I can display 9 different over the air TV channels on 9 separate screens. 9 TVs is not an option. Output resolution is not at all critical. What is the cheapest solution you can come up with?





channels

International Duo Channels Past And Present To Win Best Rock Act At World’s Largest Indie Music Awards

Follow No One, Colorado-based Vocalist Rich Hall And Portuguese Guitarist Pedro Murino Almeida, Won Best Rock Act At The 2019 JMAs In Dollywood.




channels

International Duo Channels Past And Present To Win Best Rock Act At World’s Largest Indie Music Awards

Follow No One, Colorado-based Vocalist Rich Hall And Portuguese Guitarist Pedro Murino Almeida, Won Best Rock Act At The 2019 JMAs In Dollywood.







channels

Food YouTube is the best YouTube: 6 channels to watch while you're cooped up

When you're down and troubled and need a helping hand, these food YouTubers are here to guide the way.




channels

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels [Cell Biology]

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.




channels

Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology]

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.




channels

Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology]

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.




channels

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels [Cell Biology]

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.




channels

Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources




channels

Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome [Technological Innovation and Resources]

Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale characterization of the tyrosine phosphoproteome use pTyr enrichment with pan-specific, anti-pTyr antibodies from a large amount of starting material. Methods that decrease the amount of starting material and increase the characterization depth of the tyrosine phosphoproteome while maintaining quantitative accuracy and precision would enable the discovery of tyrosine phosphorylation networks in rarer cell populations. To achieve these goals, the BOOST (Broad-spectrum Optimization Of Selective Triggering) method leveraging the multiplexing capability of tandem mass tags (TMT) and the use of pervanadate (PV) boost channels (cells treated with the broad-spectrum tyrosine phosphatase inhibitor PV) selectively increased the relative abundance of pTyr-containing peptides. After PV boost channels facilitated selective fragmentation of pTyr-containing peptides, TMT reporter ions delivered accurate quantitation of each peptide for the experimental samples while the quantitation from PV boost channels was ignored. This method yielded up to 6.3-fold boost in pTyr quantification depth of statistically significant data derived from contrived ratios, compared with TMT without PV boost channels or intensity-based label-free (LF) quantitation while maintaining quantitative accuracy and precision, allowing quantitation of over 2300 unique pTyr peptides from only 1 mg of T cell receptor-stimulated Jurkat T cells. The BOOST strategy can potentially be applied in analyses of other post-translational modifications where treatments that broadly elevate the levels of those modifications across the proteome are available.




channels

Roles of endogenous ether lipids and associated PUFA in the regulation of ion channels and their relevance for disease

Delphine Fontaine
Apr 7, 2020; 0:jlr.RA120000634v1-jlr.RA120000634
Research Articles




channels

Roles of endogenous ether lipids and associated PUFA in the regulation of ion channels and their relevance for disease [Research Articles]

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage (i.e. plasmalogens [Pls]) at the sn1 position of the glycerol backbone and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs), and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions.




channels

Delineating an extracellular redox-sensitive module in T-type Ca2+ channels [Membrane Biology]

T-type (Cav3) Ca2+ channels are important regulators of excitability and rhythmic activity of excitable cells. Among other voltage-gated Ca2+ channels, Cav3 channels are uniquely sensitive to oxidation and zinc. Using recombinant protein expression in HEK293 cells, patch clamp electrophysiology, site-directed mutagenesis, and homology modeling, we report here that modulation of Cav3.2 by redox agents and zinc is mediated by a unique extracellular module containing a high-affinity metal-binding site formed by the extracellular IS1–IS2 and IS3–IS4 loops of domain I and a cluster of extracellular cysteines in the IS1–IS2 loop. Patch clamp recording of recombinant Cav3.2 currents revealed that two cysteine-modifying agents, sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES) and N-ethylmaleimide, as well as a reactive oxygen species–producing neuropeptide, substance P (SP), inhibit Cav3.2 current to similar degrees and that this inhibition is reversed by a reducing agent and a zinc chelator. Pre-application of MTSES prevented further SP-mediated current inhibition. Substitution of the zinc-binding residue His191 in Cav3.2 reduced the channel's sensitivity to MTSES, and introduction of the corresponding histidine into Cav3.1 sensitized it to MTSES. Removal of extracellular cysteines from the IS1–IS2 loop of Cav3.2 reduced its sensitivity to MTSES and SP. We hypothesize that oxidative modification of IS1–IS2 loop cysteines induces allosteric changes in the zinc-binding site of Cav3.2 so that it becomes sensitive to ambient zinc.




channels

Central KATP Channels Modulate Glucose Effectiveness in Humans and Rodents

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this ‘glucose effectiveness’ is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). ATP-sensitive potassium channels (KATP channels) in the central nervous system (CNS) have been shown to regulate EGP in humans and rodents. We examined the contribution of central KATP channels to glucose effectiveness. Under fixed hormonal conditions (‘pancreatic clamp’ studies), hyperglycemia suppressed EGP by ~50% in both non-diabetic humans and normal Sprague Dawley rats. By contrast, antagonism of KATP channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes in rats were abolished by intracerebroventricular (ICV) administration of the KATP channel agonist diazoxide. These findings indicate that about half of EGP suppression by hyperglycemia is mediated by central KATP channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in T2D.




channels

DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels [Cell Biology]

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.




channels

Tracing the Channels Refugees Use to Seek Protection in Europe

Following the 2015­–16 crisis that saw record numbers of refugees arrive in Europe, policymakers have shown interest in creating managed, legal alternatives to the dangerous, unauthorized journeys many asylum seekers make. While these discussions should be informed by an understanding of current pathways and protection channels, it is "nearly impossible" to know how protection seekers enter and what legal channels are available to them, as this MPI Europe report explains.




channels

Legal Channels for Refugee Protection in Europe: A Pivotal Moment for Strategic Thinking

Following the release of the mid-term review of the European Agenda on Migration, this webinar offers insights from EU Member States on how existing, new, and untapped legal pathways interact with other humanitarian policies, and fit into a larger protection strategy.




channels

Deletion of Voltage-Gated Calcium Channels in Astrocytes during Demyelination Reduces Brain Inflammation and Promotes Myelin Regeneration in Mice

To determine whether Cav1.2 voltage-gated Ca2+ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca2+ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca2+ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca2+ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.

SIGNIFICANCE STATEMENT Reducing voltage-gated Ca2+ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination.




channels

Entertainment channels going with reality shows, are they playing safe?

Multiple reality shows in the same genre is a trend most GECs are following. Easy fix or strategic programming?




channels

Going beyond airways: Radio channels are monetising content on digital

The report states that this “was driven by a 3% ad volume growth”.




channels

When silence speaks volumes: US cut off ALL communication channels with Caracas after botched mercenary raid, says Maduro

Venezuelan President Nicolas Maduro has said that evidence will soon reveal the US leader himself was behind the failed incursion attempt, noting that Washington severed all remaining ties with Caracas thereafter.
Read Full Article at RT.com




channels

OnePlus devices are swapping left and right audio channels when connecting headphones

In what seems like a rather weird glitch, it appears that there is a growing number of complaints amongst OnePlus users who are finding that their headphones audio channels are being wrongly swapped when connected.




channels

Instant money transfer through social media channels

Axis Bank's Ping Pay - Instant money transfer through social media channels




channels

STIM1 interacts with termini of Orai channels in a sequential manner [RESEARCH ARTICLE]

Liling Niu, Fuyun Wu, Kaili Li, Jing Li, Shenyuan L. Zhang, Junjie Hu, and Qian Wang

Store-operated Ca2+ entry (SOCE) is critical for numerous Ca2+-related processes. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca2+ release-activated channel (CRAC) Orai on the plasma membrane. However, the molecular details of their interactions remain elusive. Here, we analyzed STIM1-Orai interactions using synthetic peptides derived from the N- and C-termini of Orai channels (Orai-NT and Orai-CT, respectively) and purified fragments of STIM1. The binding of STIM1 to Orai-NT is hydrophilic based, whereas binding to the Orai-CT is mostly hydrophobic. STIM1 decreases its affinity for Orai-CT when Orai-NT is present, supporting a stepwise interaction. Orai3-CT exhibits stronger binding to STIM1 than Orai1-CT, largely due to the shortness of one helical turn. The role of newly identified residues was confirmed by co-immunoprecipitation and Ca2+ imaging using full-length molecules. Our results provide important insight into CRAC gating by STIM1.




channels

Lidocaine Binding Enhances Inhibition of Nav1.7 Channels by the Sulfonamide PF-05089771 [Articles]

PF-05089771 is an aryl sulfonamide Nav1.7 channel blocker that binds to the inactivated state of Nav1.7 channels with high affinity but binds only weakly to channels in the resting state. Such aryl sulfonamide Nav1.7 channel blockers bind to the extracellular surface of the S1-S4 voltage-sensor segment of homologous Domain 4, whose movement is associated with inactivation. This binding site is different from that of classic sodium channel inhibitors like lidocaine, which also bind with higher affinity to the inactivated state than the resting state but bind at a site within the pore of the channel. The common dependence on gating state with distinct binding sites raises the possibility that inhibition by aryl sulfonamides and by classic local anesthetics might show an interaction mediated by their mutual state dependence. We tested this possibility by examining the state-dependent inhibition by PF-05089771 and lidocaine of human Nav1.7 channels expressed in human embryonic kidney 293 cells. At –80 mV, where a small fraction of channels are in an inactivated state under drug-free conditions, inhibition by PF-05089771 was both enhanced and speeded in the presence of lidocaine. The results suggest that lidocaine binding to the channel enhances PF-05089771 inhibition by altering the equilibrium between resting states (with D4S4 in the inner position) and inactivated states (with D4S4 in the outer position). The gating state–mediated interaction between the compounds illustrates a principle applicable to many state-dependent agents.

SIGNIFICANCE STATEMENT

The results show that lidocaine enhances the degree and rate of inhibition of Nav1.7 channels by the aryl sulfonamide compound PF-05089771, consistent with state-dependent binding by lidocaine increasing the fraction of channels presenting a high-affinity binding site for PF-05089771 and suggesting that combinations of agents targeted to the pore-region binding site of lidocaine and the external binding site of aryl sulfonamides may have synergistic actions.




channels

[Cell Signaling] Store-Operated Calcium Channels: From Function to Structure and Back Again

Store-operated calcium (Ca2+) entry (SOCE) occurs through a widely distributed family of ion channels activated by the loss of Ca2+ from the endoplasmic reticulum (ER). The best understood of these is the Ca2+ release-activated Ca2+ (CRAC) channel, which is notable for its unique activation mechanism as well as its many essential physiological functions and the diverse pathologies that result from dysregulation. In response to ER Ca2+ depletion, CRAC channels are formed through a diffusion trap mechanism at ER–plasma membrane (PM) junctions, where the ER Ca2+-sensing stromal interaction molecule (STIM) proteins bind and activate hexamers of Orai pore-forming proteins to trigger Ca2+ entry. Cell biological studies are clarifying the architecture of ER–PM junctions, their roles in Ca2+ and lipid transport, and functional interactions with cytoskeletal proteins. Molecular structures of STIM and Orai have inspired a multitude of mutagenesis and electrophysiological studies that reveal potential mechanisms for how STIM is toggled between inactive and active states, how it binds and activates Orai, and the importance of STIM-binding stoichiometry for opening the channel and establishing its signature characteristics of extremely high Ca2+ selectivity and low Ca2+ conductance.




channels

MAGA channels the fury of the Chilean protests on ‘Calma’

All the profits from the track will go to the Brigada Cascos Rojos, an independent aid squad set up to help those affected by the riots. Chilean producer MAGA channels the fury of the civil protests taking place throughout Chile in the moody visual from Juegos Artificiales for their new track, ‘Calma’. “On October 18 […]

The post MAGA channels the fury of the Chilean protests on ‘Calma’ appeared first on FACT Magazine.




channels

YouTube TV subscribers getting access to Viacom channels including VH1, BET, MTV and others

MTV, Nickelodeon, Paramount Network and TV Land are among the channels launching on YouTube TV in the coming months.

      




channels

The Duchess of Cambridge channels French girl chic for virtual interview about the NHS, coronavirus and mental health

She and Prince William dialled in from their Norfolk home




channels

The Drug Channels Coronavirus Industry Impact Survey

It’s a unique and troubling time. We are all of course concerned about the coronavirus and its disruption to our personal and professional lives.

I presume that life will return to normal later this year. But what happens then? Will there be long-term changes to how the drug channel operates? Will we see permanent changes in behavior, policy, and industry structure?

To answer these questions, I want to tap the collective insights of Drug Channels’ 30,000+ audience.


This survey should take 10 minutes or less. I will provide a full review of the results next week on Drug Channels. The survey will close on March 20.

You can respond anonymously. Any information you provide will be kept confidential. Per Drug Channels' long-standing policy, I never publish, release, or disclose any personal data without your permission.

Thanks in advance for sharing your insights.

Regards,
Adam

        




channels

Drug Channels News Roundup, March 2020: Sanofi’s Gross-to-Net Bubble, Drug Pricing Findings, Amazon Replaces Express Scripts, and Drug Channels Video

First, let me say thank you to all of the healthcare workers who are putting themselves at risk during this crisis.

As I noted last week, many of the crucial issues for our healthcare system will remain after we all get through this challenging period. In that regard, here’s a look at some noteworthy news from the past month:
  • Sanofi discloses new data about insulin prices
  • Excellent new academic research on list vs. net drug prices
  • Three notable researchers overturn their earlier research on drug costs
  • Amazon switches PBM vendors for some of its employees
Plus, we unveil the teaser trailer for Drug Channels Video!

P.S. Join the more than 9,000 followers of my daily links to neat stuff at @DrugChannels on Twitter. My recent tweets have highlighted such topics as:
  • How GoodRx shares patients’ prescription data
  • 2019 drug trend at Prime Therapeutics
  • Controversy about the independent pharmacy market
  • A new $5 generic mail order program, Medicare Part D reform
  • Retail pharmacy’s future
  • Job openings at Amazon 
  • Frozen cookie dough
  • And much more!
I have also been tweeting many under-the-radar stories about how the coronavirus affects drug channels.
Read more »
        




channels

Introducing: Drug Channels Video!

In 2006, I launched the Drug Channels website to explore the economics of the U.S. reimbursement and distribution system for prescription pharmaceuticals. More than 30,000 professionals in the pharmaceutical and related industries rely on Drug Channels for timely analysis and provocative, fact-based insights.

Today, I am pleased to announce the launch of our new delivery platform: Drug Channels Video!

You can look forward to:
  • Information and analysis via our new YouTube channel (Never fear. I’ll still be publishing articles on the website every week.)
  • Livestream video webinars (Stay tuned next week for an announcement about our first two events.)
  • Private, live virtual keynotes and remote presentations (Email me to schedule a safe social distancing event for your team.)
  • Online video courses (Coming later in 2020)
Please watch my brief video introduction below. (Click here if you can’t see the video.)



I hope you and your families stay safe and healthy in these challenging times. I look forward to reconnecting with you in person soon.

        




channels

Drug Channels News Roundup, April 2020: Drug Pricing Outlook, COVID-19 Data Tracker, Community Oncology Clinics, and My Favorite Chart of 2020

Rumor has it that Spring has finally reached our worldwide headquarters here in beautiful downtown Philadelphia. (See photo at right.) While we wait to go outside, please enjoy this month’s selection of noteworthy news:
  • The outlook for drug prices
  • A outstanding (and free!) resource for tracking COVID-19 daily data
  • What’s up with community oncology practices?
Plus, I share my favorite chart of 2020 (so far).

P.S. Join the more than 9,200 followers of my curated links to neat stuff at @DrugChannels on Twitter. My recent tweets have highlighted: Prime Therapeutics new gene therapy offering, AmerisourceBergen’s laudable deal with the Justice Department, the Costco/Instacart deal, Rite Aid’s new CEO, clinical trial trends, vaccine pricing, and much more! I have also been tweeting under-the-radar stories about how the coronavirus is affecting drug channels.

Tomorrow (May 1), Drug Channels Institute will host the first of two live video webinars: Industry Update and COVID-19 Impact: Retail & Specialty Pharmacies. We'll host the second video webinar—Industry Update and COVID-19 Impact: PBMs & Payers—on May 8. CLICK HERE TO LEARN MORE AND SIGN UP. Contact Paula Fein (paula@drugchannelsinstitute.com) for our special promo codes for multiple viewing sites. DCI will donate 20% of all profits from these events to The Center for Disaster Philanthropy’s COVID-19 Response Fund.

Read more »
        




channels

Insurers + PBMs + Specialty Pharmacies + Providers: Will Vertical Consolidation Disrupt Drug Channels in 2020? (rerun)

This week, I’m rerunning some popular posts while I prepare for this Friday’s video webinar: Industry Update and COVID-19 Impact: PBMs & Payers.

Life was very different when I originally published today’s article. 2020 is not turning out to be quite what any of us expected. However, the pandemic has exposed some intriguing pros and cons of vertical consolidation. Click here to see the original post and comments from December 2019.


The largest insurers, PBMs, and specialty pharmacies have now combined into vertically-integrated organizations. As I explain below, these companies have also been rapidly integrating with healthcare providers.

I also provide an updated look at these companies and highlight strategies that they are using—or could use—to control the channel. I believe that these insurer / PBM / specialty pharmacy / provider organizations are poised to restructure U.S. drug channels by exerting greater control over patient access, sites of care/dispensing, and pricing.

If they can effectively coordinate their sprawling business operations, they will pose a substantial threat of disruption to the existing commercial strategies of pharma companies.

Will they succeed by better managing care and costs, or merely by extracting higher profits from our convoluted system?
Read more »
        




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