Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

NEW YORK (AP): When it comes to the 2025 Grammy Award nominations, Cowboy Carter rules. Its superstar singer, Beyonce, leads the nods with 11, bringing her career total to 99 nominations. That makes her the most nominated artiste in Grammy history...

Long hailed as dancehall's most controversial figure, Vybz Kartel has always commanded the spotlight with his edgy lyrics and unfiltered persona. But since his release from prison in July, Kartel has begun to show a surprising transformation that'...

28 July 2020

En fonction de leurs causes, les douleurs du côté droit peuvent se manifester de différentes manières. Les symptômes de ces douleurs peuvent également varier d’une personne à une autre. Certaines personnes décrivent les douleurs du côté comme des sensations de crampes, de brûlures ou de piqûres. D’autres en revanche parlent de douleurs sourdes ou lancinantes qui irradient […]

L’article Douleurs côté droit sous les côtes : comment les soulager naturellement est apparu en premier sur Ortho Doc France.

Gêne constant, difficulté à respirer : avez-vous une impression de glaires coincées dans la gorge actuellement ? Cette impression peut être due à plusieurs facteurs parfois bénignes mais aussi graves. Fort heureusement, il existe quelques astuces naturelles qui vous permettront d’avoir un soulagement en attendant de consulter un médecin ORL. Mais avant, l’impression de glaires coincées dans la gorge est […]

L’article Comment se débarrasser des glaires coincées dans la gorge ? est apparu en premier sur Ortho Doc France.

The battle for truth: The BBC's role at 100 22 November 2022 — 6:30PM TO 7:30PM Anonymous (not verified) 13 October 2022 Chatham House and Online

Tim Davie, director general of the BBC, and others discuss how the BBC shapes, and is shaped by, the world today.

This year, the BBC turns 100 and the World Service 90 in a world facing crises of increasing scale and frequency and in an age of disinformation, democratic disruption and a growing assault on truth and free reporting worldwide. What does this mean for Britain’s foremost news provider at home and across the globe?

This conversation considers:

• How does the BBC navigate a drastically changing media landscape?

• What does the BBC represent in the UK and to the world?

• What ‘soft power’ does the BBC have and how does it use it best?

As with all members events, questions from the audience drive the conversation.

Read the transcript. 

Wyoming once again takes the top spot in Quality Counts' annual ranking of the states on school finance, while 22 states receive grades between C-minus and D-minus.

New Jersey leads the states on Quality Counts 2020’s summative rankings based on previous years’ data. But the annual report card shows plenty of work needed all around as the pressure mounts.

New Jersey leads the states on Quality Counts 2020’s summative rankings based on previous years’ data. But the annual report card shows plenty of work needed all around as the pressure mounts.

Advocates argue the need is greater than ever and that failure to press school funding lawsuits in this moment would be a missed opportunity.

Wyoming once again takes the top spot in Quality Counts' annual ranking of the states on school finance, while 22 states receive grades between C-minus and D-minus.

Taylor Swift and Beyoncé have achieved a degree of power in the music industry that singer/songwriters of earlier eras like Joan Baez—as the folk icon tells us—never even contemplated. Six decades ago, Baez was part of a folk revival that regarded music not merely as entertainment but as a vessel for political engagement and social change. In the documentary Joan Baez: I Am a Noise, the now-83-year-old musician and activist reflects on her career and legacy. Smithsonian senior editor Jennie Rothenberg Gritz interviewed Baez about the film and about the shifting intersection of art and activism. We present excerpts from that conversation in this episode. Then, veteran music critic Evelyn McDonnell discusses how the political dimensions of pop music have changed since Baez’s era, and what it means that many fans now look Beyoncé and Taylor Swift not just for great music, but for comment on the state of the world. Clips from Joan Baez: I Am a Noise in this episode are used with permission from Magnolia Pictures & Mead Street Films. Learn more about that film here (https://www.magpictures.com/joanbaez/) . Evelyn McDonnell’s latest book is The World According to Joan Didion (https://www.harpercollins.com/products/the-world-according-to-joan-didion-evelyn-mcdonnell?variant=41001679487010) . You can learn more about Evelyn and her work at her site, Populism (https://populismblog.wordpress.com/about-2/) . Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Rye Dorsey, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Fact-checking by Stephanie Abramson. Episode artwork by Emily Lankiewicz. Music by APM Music.

Bobby Smyrniotis, shut out in five previous nominations, finally has a Coach of the Year Award to go with his four Canadian Premier League titles.

The Calgary-based team beat Hamilton Forge FC in a 2-1 nail-biter at home on Saturday, in front of a sold-out crowd of over 7,000 fans at Spruce Meadows.

Apple Musicis turning its "100 Best Albums" list into a luxurious collectible book, bringing iconic records from the screen to your shelf.

The Penn State School of Music's annual "Mosaic" concert will return to Eisenhower Auditorium on Sunday, Dec. 8 at 4 p.m. 

Por años, Gustavo*, un arquitecto de América Central, se sintió llamado a trabajar en la Península Arábiga. Finalmente, se presentó la oportunidad de realizar un viaje de corto plazo para ver cómo sería utilizar su profesión en el exterior.

DNREC announced that the Michael N. Castle Trail along the C&D Canal has been reopened at the South Lums Parking Area following repairs to a section of the trail damaged in March by storms.

Staying ahead of the curve is essential to meeting customer needs. Cadence has consistently demonstrated its commitment to innovation, and its latest IP portfolio available on TSMC's 3nm (N3) process is no exception. Today, rapid advancements in AI/ML, hyperscale computing (HPC), and the automotive industry are driving significant changes in technology. Let's explore the impressive array of IP that Cadence offers on this advanced node.

Memory Solutions: High-Speed and Power-Efficient

Cadence's DDR5 12.8G MRDIMM IP supports the highest speed grade Gen2 MRDIMMs and features a fully hardened PHY optimized to the customer's floorplan. The LPDDR5X IP is silicon-proven at 9.6Gbps and is ideal for power-sensitive applications, offering a fully integrated memory subsystem.

GDDR7: Leading the Way in Graphics Memory

Cadence has achieved a significant milestone with the world's first silicon-proven GDDR7 IP, supporting data rates up to 32Gbps. This IP offers the best price/performance ratio for AI interfaces, making it a game-changer in the graphics memory domain.

PCIe and CXL Solutions: Robust and Reliable

Cadence's PCIe 3.0 IP is a mature and production-proven solution available across a wide range of process nodes from 28nm to 3nm. It offers a versatile multi-link architecture for optimum SoC configurability and flexible use cases. The PCIe 6.0 and CXL 3.x solutions are silicon-proven, power-optimized, and highly robust, with jitter-tolerant capabilities. These IP are the only subsystem proven with eight lanes of controller and PHY in silicon, ensuring interoperability with leading test vendors and OEMs.

UCIe PHY: Setting New Standards

The UCIe PHY IP from Cadence are set to be generally available after successful silicon characterization in both standard and advanced package options on the TSMC N3 (3nm) process. These IP demonstrate significantly better power, performance, and area (PPA) metrics than the specifications, with a bit error rate (BER) better than 1E-27 compared to the spec of 1E-15. The power consumption is also notably lower than the spec limit, ensuring a simpler integration with a best-in-class power profile.

112G PHY IP: Pushing the Boundaries of Performance

Cadence's 112G PHY IP are designed to meet the demands of high-speed data transmission. The 112G-ULR PHY IP, characterized in the 3nm process, showcases exceptional performance with support for insertion loss over 45dB at data rates ranging from 1.25Gbps to 112.5Gbps. This IP is optimized for both power and area, making it a versatile choice for various applications. The 112G-VSR/MR PHY IP also stands out with its excellent power and performance metrics, making it ideal for short-reach applications and optical interconnects. Additionally, the 112G PAM4 PHY solutions cater to hyperscale, AI, HPC, and optics applications, featuring a mature DSP-based SerDes architecture with advanced techniques such as reflection cancellation.

Cadence's IP portfolio on TSMC N3 shows innovation and expertise to solve today's design challenges. From high-speed PHY IP to robust PCIe and CXL solutions and advanced memory IP, Cadence continues to lead the way in semiconductor IP development. These solutions not only meet but exceed industry standards, ensuring that customers can confidently achieve their design goals. Stay tuned for more updates on Cadence's groundbreaking advancements in semiconductor technology.

Learn more about Cadence IP and other silicon solutions.

hello:

i use the command "net logic" to change/assign the net name of the pins but the command can be used for only one pin at a time.

is there a way to change/assign the same net name on 100 pins all at once?

i have a daisy chain design so i need to assign one net name for 100s of pins.

========

thank you david, i was able to do it.

i am writing this section because i can not reply to your comment.

I'm currently work in coverage analysis. In my design certain register bits remain unused, which could potentially lower toggle coverage. Specifically, I'd like to know how to disable coverage for specific unused register bits within a 32-bit register. For instance, I want to deactivate coverage for bit 17 and bit 20 in a 32-bit register to optimize toggle coverage. Could you please provide guidance on how to accomplish this?

BAKU, Azerbaijan — The head of the United Nations' nuclear watchdog said Tuesday he's hopeful that meetings this week with Iranian officials, including the country's new president, can lead to a breakthrough in monitoring the country's nuclear program, a longstanding issue that has gained new urgency as Israel has twice struck Iran amid rising tensions in the Middle East. Rafael Mariano Grossi, director general of the International Atomic Energy Agency, will travel to Iran on Wednesday to meet for the first time with President Masoud Pezeshkian, who was elected in July. Grossi said he hopes to build on positive discussions he had with Iranian Foreign Minister Abbas Araghchi during the U.N. General Assembly in September. "We have a problem that we need to solve," Grossi said in an interview at the U.N. climate conference in Azerbaijan. "That is this gap, this lack of confidence, which we should not allow to grow into a self-fulfilling prophecy of using nuclear facilities as targets." He added: "There has been a bit of a dire straits dynamic with Iran that we want to go beyond." Iran is rapidly advancing its atomic program while increasing stockpiles of uranium enriched to near weapons-grade levels, all in defiance of international demands, according to the IAEA. Iran says its program is for energy purposes, not to build weapons. Grossi's visit comes as Israel and Iran have traded missile attacks in recent months after more than a year of war in Gaza, which is governed by Hamas, a group supported by Iran. Grossi noted that international law prohibits the attack of nuclear facilities and "it's obvious that is something that can have radiological consequences." The Biden administration said last month that it had won assurances from Israel that it would not attack nuclear or oil sites. A 2015 nuclear agreement between Iran and world powers put limits on Iran's nuclear program, which the West fears could be used to make nuclear weapons. The deal included the lifting of economic sanctions on Iran. But that deal collapsed after Donald Trump's administration in 2018 pulled the United States from it. That led Iran to abandon all limits put on its program and enrich uranium to up to 60% purity. When asked if the IAEA feared Iran may be developing a bomb, Grossi said he didn't "have any information that would sustain that." He added that inspectors' job was not to "judge intentions," but rather verify that what Iran says about its nuclear program was true. Trump's reelection last week raises questions about whether and how the incoming administration and Iran may engage. Grossi said he had worked with the first Trump administration, which he said engaged in "seamless, professional work," and looked forward to looking with Trump's second administration. "Circumstances have changed in that the problem has grown bigger than it was," said Grossi. "The problem of not finding a solution."

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día.

Britney Spears responds to ex husband Kevin Federline's claims with subtle moveBritney Spears has responded to claims made by her ex-husband, Kevin Federline, regarding her recent reunion with their son, Jayden.The Toxic hitmaker took to her Instagram to share another cryptic post with her...

Yale University introduces Beyoncé course: Deets insideBeyoncé’s fans are in for a surprise as Yale University has announced a new course centering on the singer and her iconic legacy.According to Yale Daily News, the new students will “dive deep” into...

Margot Robbie uses the ultimate emotionally packed movie to cry in movies, and that’s what she did in the Wolf of Wall Street.In a yet-to-be-released episode of the Talking Pictures: A Movie Memories Podcast, which premiers on Nov. 26, the actress was recently questioned how she...

Title: Changes to CDC's COVID-19 Testing Guidelines Trigger Concern
Category: Health News
Created: 8/26/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM

Title: Little Change in Number of Uninsured in Pandemic's First Year
Category: Health News
Created: 8/23/2021 12:00:00 AM
Last Editorial Review: 8/24/2021 12:00:00 AM

Sega are delisting several bundles of 'classic' games from digital stores, along with "select individual" games. On Steam specifically, this adds up to over 60 games in total, including several actual classics including the original Streets Of Rage trilogy, Crazy Taxi, and Jet Set Radio.

The games will be removed on December 6th but will remain playable to those who already own them.

Read more

The developers of hero shooter Overwatch 2 must have dropped a box full of old photographs while clearing the attic, spilling old snapshots of Route 66 onto the floor and getting snared in a nostalgic daze. The game is launching a "Classic" mode today that will let you play the first-person payload pusher as it (mostly) was back in 2016 when the first Overwatch launched. That means 6v6 fights, the original abilities of its heroes, and no limits to stop the entire team picking the same character.

Read more