Current prices are now a deal, get them while you can or cancel your subscription in protest. Many vendors have already increased prices.

https://www.forbes.com/sites/erikkain/2023/08/31/time-to-cancel-playstation-plus-as-sony-quietly-raises-prices-through-the-roof/?sh=e43dfc0c9ac6

Uncanny Valley-$2.59

Batman: Arkham Collection-$5.99

Ends 11/2/2023

Short breaks are among the most fundamental services for supporting families with disabled children. By providing breaks from caring and positive experiences for children and young people, they allow parent carers to focus on relationships with other children, or to have time to themselves or with their partner, leading to lower levels of psychological distress, higher levels of life satisfaction and better health. As a result, fewer parent carers reach ‘breaking point’ and fewer children require access to emergency provision or enter the looked after system. This report, commissioned by Every Disabled Child Matters, looks at the current provision of short breaks to families of disabled children in England.

The Scottish Council for Voluntary Organisations (SCVO) is the membership organisation for Scotland's charities, voluntary organisations and social enterprises.

New on Latin Leche, a Say Uncle site: You are horny all day at your job and you just can’t wait to get home and fuck your main squeeze… and fuck they just want to argue, talk about blue balls! So, you head to the gym and after an intense session you enter the sauna….... View Article

The post Say Uncle | Latin Leche: Rodrigo El Santo and Alexander Rajesh appeared first on QueerClick.

(Image credit: catcurio)

There exists a delightful subreddit called Council of Cats. This is where you'll find groups of cats having important discussions of matters both urgent and mundane. I have four cats, and I find it difficult to get all of them in one picture if they aren't asleep, so seeing many cats getting along is really nice. You can often guess what they are discussing at their council meeting, or they might be enjoying some group activity like birdwatching or annoying their human. They often get together to make demands on your time, or in other words, they gang up to get what they want.  

(Image source: reddit)

But there are also pictures that show cats just like each other's company. Bored Panda has collected 50 of the most amusing photographs from Council of Cats to give us a taste of a cat colony's strength in numbers, presented in a ranked list for your amusement.

The discovery of an impeccably preserved Celtic burial chamber in southern Germany is a "stroke of luck for archaeology," scientists say.

Welcome to the first episode of the Internet Musician Podcast! Show notes for Episode #1: Subscribe to the Internet Musician Podcast with iTunes: The first episode of The Internet Musician Podcast, hosted by indie artist and internet music marketing junkie Brian Hartzog (http://www.brianhartzog.net).  In this introductory episode, Brian introduces himself, his indie music credentials and […]

Two projects — one that maps the function of the brain’s neuronal network in unprecedented detail and another that combines robotics and light-based computer circuits to create safe self-driving vehicles — have been awarded funding through Princeton’s Eric and Wendy Schmidt Transformative Technology Fund.

The AO3 Fanzine Scan Hosting Project (FSHP) is a partnership between the Open Doors committee and fan-run preservation project Zinedom through which fanfiction and fanart originally published in print fanzines is imported to the Archive of Our Own. Fanworks can be imported to AO3 with the consent of either the creators of the works or the publisher of the fanzine in which the fanworks were published.

Today, Open Doors is pleased to announce a list of collections that it has created since September 2023 to house fanworks imported through the FSHP. A collection has been created for each fanzine from which one or more fanworks have been imported, but these collections do not contain every work from each of these zines, and many so far only include one work each in cases where Open Doors only has permission to import that particular work. For full transparency, Open Doors plans to continue to announce collections as they are created that may or may not grow with additional fanworks as additional permissions are obtained from more creators in the future.

As of August 2024, Open Doors has created the following collections to represent fanzines from which it has imported works:

• A Portfolio of Poetry and Portraits
• Amazing Grace
• Astray in the Wilderness
• Beyond Dreams
• Broken Images
• California K/S
• Contact
• CrosSignals
• Daring Attempt
• Enter-comm
• First Time
• Gateway
• Guardian
• Happy Tails
• IDIC
• In the Wilderness
• KaleidoScope
• KisMet
• KSX
• Legacy
• Legends
• Naked Times
• Nightvisions
• Nome
• On the Edge
• One Shot
• Partners
• Potpourri
• Pushin' the Odds
• Quantum Chain
• Scattered Stars
• Sehlat's Roar
• Southern Star
• Spock's Arthropods
• Strange Justice
• The Complete Rack
• The K/S Press
• The Rack & All the King's Horses All the King's Men
• Three Eleven
• Universe Beyond
• Whalesong
• Within the Mirror

For answers to frequently asked questions, please see the FSHP page on the Open Doors website. If you'd like to give Open Doors permission to import any of your fanworks that have been previously published in print fanzines, or if you have any other FSHP-related queries, please contact the Open Doors Committee.

We'd also love it if fans could help us preserve the story of any fanzines in which they may have been published on Fanlore. If you're new to wiki editing, no worries! Check out the new visitor portal, or ask the Fanlore Gardeners for tips.

Thanks for your interest in preserving fannish history for future generations of readers!

- The Open Doors team

Commenting on this post will be disabled in 14 days, on 18 November. If you have any questions, concerns, or comments regarding this import after that date, please contact Open Doors.

Are you curious to learn more about Excel? Interested in refining your Excel skills? Wondering if you can use it more effectively? Join us for this introduction to Excel functions workshop. We will discuss using Excel functions, as well as working with text and dates. No previous knowledge required.

The collection includes new Trail and Enduro apparel lines for women, plus Gravity jerseys and pants for men developed alongside Bernard Kerr.
( Photos: 21, Comments: 46 )

The new books capture all the storylines of the 2024 racing season in stunning photography, reporting and analysis
( Photos: 15, Comments: 15 )

As the first-ever “full-scale planetary defense test” to deflect a space rock, the DART mission aims to show that protecting Earth from a hazardous asteroid is possible.

Here’s what the largest—and most expensive—infrared space telescope will set its sights on.

NASA’s massive SLS rocket and Orion spacecraft kick off a series of missions to put humans back on the Moon.

StarBoard Solution EU, has collaborated with Repeat Software, a UK software developer of Repeat Signage software, to provide a digital signage solution for StarBoard users.

Kids at a tribal school in Arizona are preparing for their own election to determine their favorite school lunch: pizza or chicken nuggets? And they're learning about democracy along the way.

By Mariane Angela Democratic New York City Mayor Eric Adams’ office announced Thursday that New York City will stop providing food vouchers to migrants, CBS News New York reported. NYC will phase out out a program that gave prepaid debit cards to migrant families in city-funded hotels to purchase their own meals and essentials, according to […]

The post NYC Mayor Eric Adams Announces End To NYC Food Vouchers For Illegal Immigrants appeared first on Liberty Unyielding.

By Reagan Reese President-elect Donald Trump announced Thursday that his 2024 campaign manager, Susie Wiles will be his Chief of Staff in his administration. Wiles, who led Trump’s return to the White House alongside Chis LaCivita, has largely been praised for her disciplined and professional operation in the 2024 run. Heading up Trump’s second administration, […]

The post Trump Announces Susie Wiles As Chief Of Staff appeared first on Liberty Unyielding.

As heads of Arab and Islamic states meet in Riyadh, Trump's victory raises questions for the region.

Maia Bouchier and Freya Kemp could make their Test debuts after being included in the squad for England's tour of South Africa.

Uncapped batter Nathan McSweeney will open for Australia in the first of five Tests against India.

Analyst Alex de Waal looks at how the US president-elect could deal with conflicts on the continent.

Built in 1865, The Crossness Pumping Station is famed for it's wrought-iron decoration.

They will be performing one final time at this year's Remembrance Sunday commemorations in Dagenham.

The government may send envoys to oversee decisions taken by the independent mayor of Tower Hamlets.

A video surfaced on social media Friday showing the Democratic presidential nominee Joe Biden speaking to overseas U.S. service members where he called them “stupid bastards” and a “dull bunch.” During his last few months as Vice President, Biden in 2106 visited Al-Dhafra Air Base near the United Arab Emirates capital of Abu Dhabi and […]

The post Biden Calls U.S. Troops In 2016 ‘Stupid Bastards’ And A ‘Dull Bunch’ appeared first on Hispolitica.

Trump 2020 reelection campaign announced Saturday for the final month before Election Day the launch of “Operation MAGA,” that will consist of a “full marshaling of top-level surrogates, campaign coalitions and Trump supporters to rally behind the president and carry the campaign forward” until President Trump recovers from COVID-19 and can return on the campaign […]

The post Trump Campaign Launches ‘Operation MAGA’ appeared first on Hispolitica.

The Football Association launches its own investigation into the video that appears to show Premier League referee David Coote using foul language to describe former Liverpool boss Jurgen Klopp.

Turkish football club Ankaragucu defend their former president Faruk Koca after he was sentenced to jail for assaulting a referee.

1. Coldplay announces fourth show in Ahmedabad on 25 January. Tickets available from… | Today News  Mint
2. Coldplay announces new show in Ahmedabad: Check date, how to book tickets and more  India Today
3. Coldplay Announces Fourth Concert In India. Check Out Date, Venue And Ticket Prices  NDTV Movies
4. Coldplay announces new show in Ahmedabad, check details here  CNBCTV18
5. entertainment News Live Today November 13, 2024: Coldplay announced 4th India show in Ahmedabad: Check out ticket sale details  Hindustan Times

1. iPhone SE 4 expected to launch in March 2025, supply chain data suggests  Business Standard
2. iPhone SE4 is likely to launch soon and here are 5 big upgrades we are expecting  India Today
3. Apple iPhone SE 4 to launch next year, likely to become the cheapest iPhone to support Apple Intelligence...  Moneycontrol
4. iPhone SE 4 may spell trouble for iPhone 16 and premium Android phones, here’s why  Hindustan Times
5. iPhone SE 4 Camera Production to Begin Soon Ahead of Anticipated Debut in March 2025: Report  Gadgets 360

The leader of the world's Anglican communion, Archbishop of Canterbury Justin Welby, announced Tuesday he was resigning following a damning report that concluded the Church of England covered up a serial abuse case.

velocityconf: Help your dev + ops teams be cross-functional and more successful. http://t.co/1mqGK3zh0U Free webcast 5/22 w/ @lnxchk

Tuesday 12 November 2024 – Best Wallet ($BEST) sold out its first presale stage in just six hours, raising $162,000… Continue reading Best Wallet’s Presale Generates $162K in 6 Hours, Sells Out on Launch Day

The post Best Wallet’s Presale Generates $162K in 6 Hours, Sells Out on Launch Day appeared first on ReadWrite.

Continuing to set records, Pepe Unchained recently achieved a new milestone after reaching $26 million. The project’s presale has now… Continue reading As Pepe Unchained Launch Date Nears, Analyst Makes ‘Massive’ Prediction For PEPU

The post As Pepe Unchained Launch Date Nears, Analyst Makes ‘Massive’ Prediction For PEPU appeared first on ReadWrite.

November has turned into a remarkable month for cryptocurrency, with Bitcoin and meme coins like Dogecoin, Shiba Inu, and Pepe… Continue reading Meme Coins Are Soaring as Pepe Unchained Layer 2 ICO Raises $27.5 Million

The post Meme Coins Are Soaring as Pepe Unchained Layer 2 ICO Raises $27.5 Million appeared first on ReadWrite.

The following article, Left Already Losing It As Trump Announces Starting Lineup (Video), was first published on Conservative Firing Line.

Trump learned some hard lessons from his first kick at the can. This time, he’s not making the same mistakes. Personnel IS policy. Last time around DJT was hamstrung right out of the gate when the Alabama Senator he tapped to be his AG was stuck in purgatory under bogus Russia allegations. The Deep State …

Continue reading Left Already Losing It As Trump Announces Starting Lineup (Video) ...

You know it's bad when you give the Democrats a whoopin and the corprate media clowns have no choice but to concede your point.

The post GLORIOUS: Scott Jennings Gets Van Jones To Cry ‘Uncle’ Live On CNN appeared first on Clash Daily.

He learned some hard lessons from his first kick at the can. This time, he's not making the same mistakes. Personnel IS policy.

The post Left Already Losing It As Trump Announces His Starting Lineup (VIDEO) appeared first on Clash Daily.

Labour Party Conference – International affairs networking brunch 24 September 2024 — 11:00AM TO 12:00PM Anonymous (not verified) 16 September 2024 Labour – Grace 1 Suite, Hilton Hotel, Liverpool

Hosted by Sir Simon Fraser, Chairman of Chatham House.

This event is taking place at the Hilton Hotel, Grace 1 Suite, Liverpool.

You are warmly invited to join us for an exclusive networking brunch at the 2024 Labour Party Conference.

Sir Simon Fraser, Chairman of Chatham House, and Olivia O’Sullivan, Director of Chatham House’s UK in the World Programme, will deliver opening remarks, followed by an interactive networking session where you will have the chance to engage with a wide range of stakeholders. Join us to connect with key senior parliamentary, corporate and media attendees at the Labour Party Conference.

This event will be taking place outside of the secure zone.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.

The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases.

IQGAP1 is a key scaffold protein that regulates numerous cellular processes and signaling pathways. Analogous to many other cellular proteins, IQGAP1 undergoes post-translational modifications, including phosphorylation. Nevertheless, very little is known about the specific sites of phosphorylation or the effects on IQGAP1 function. Here, using several approaches, including MS, site-directed mutagenesis, siRNA-mediated gene silencing, and chemical inhibitors, we identified the specific tyrosine residues that are phosphorylated on IQGAP1 and evaluated the effect on function. Tyr-172, Tyr-654, Tyr-855, and Tyr-1510 were phosphorylated on IQGAP1 when phosphotyrosine phosphatase activity was inhibited in cells. IQGAP1 was phosphorylated exclusively on Tyr-1510 under conditions with enhanced MET or c-Src signaling, including in human lung cancer cell lines. This phosphorylation was significantly reduced by chemical inhibitors of MET or c-Src or by siRNA-mediated knockdown of MET. To investigate the biological sequelae of phosphorylation, we generated a nonphosphorylatable IQGAP1 construct by replacing Tyr-1510 with alanine. The ability of hepatocyte growth factor, the ligand for MET, to promote AKT activation and cell migration was significantly greater when IQGAP1-null cells were reconstituted with IQGAP1 Y1510A than when cells were reconstituted with WT IQGAP1. Collectively, our data suggest that phosphorylation of Tyr-1510 of IQGAP1 alters cell function. Because increased MET signaling is implicated in the development and progression of several types of carcinoma, IQGAP1 may be a potential therapeutic target in selected malignancies.

The near death and uncertain future of the US National Security Council 27 January 2023 — 9:00AM TO 10:00AM Anonymous (not verified) 9 January 2023 Chatham House

What role should the US National Security Council play in an era of great power competition?

Please plan to arrive at Chatham House from 08:45 GMT as the event will begin promptly at 09:00 GMT

Over the last three years, the US National Security Council (NSC) has gone from being neglected to necessary again, in Washington.

After former US President Donald Trump ignored and then tried to dismantle the NSC, current US President Joe Biden has restored the body but chosen not to reform it.

Born in the days before the Cold War and empowered during the War on Terror, what role should the NSC play in an era of great power competition?

Plus, how must it, and the rest of Washington, evolve to meet the challenges and opportunities that remain in the 21st century?

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research