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We got married at a luxury resort in Thailand. If I could go back, there are 5 things I'd do differently.

Looking back, Ellie Furuya says her wedding reception in Thailand was too adult-centric. If she could go back, she'd make it more kid-friendly.




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SoftBank is Nvidia's first Blackwell chips customer. Here's what they're going to be used for.

The collaboration comes amid skyrocketing demand for Nvidia chips, as companies scramble to secure supplies.




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Ford is slashing hours for some German factory employees amid lower EV demand

The carmaker has more than 4,000 employees at its Cologne plant. It also has another plant in Saarlouis, in southwestern Germany.




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Three Benefits of Promoting Digital Goods and Software Products

Are you dreaming of being your own boss someday, or would you like to bring in extra income? Starting an online business is one of the easiest ways to accomplish this. The biggest challenge of starting an online business can be developing your business plan. If you are struggling to come up with that brilliant […]




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News24 | Mozambique deploys soldiers ahead of planned protests

Soldiers and police were patrolling Mozambique's capital Maputo early on Thursday ahead of a planned protest against election results seen by the opposition as fraudulent.




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News24 | Lesotho to ban importation of bottled water

Lesotho's national assembly has passed a motion to ban the importation of bottled water into the country as part of measures to promote the local industry.




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News24 | Somalia insists Ethiopia will not be part of new AU mission

Somalia insisted Saturday that Ethiopia will not be part of a new African Union peacekeeping mission, as the two nations remain locked in a dispute that has sent shivers through the Horn of Africa.




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News24 | SA sold Côte d'Ivoire R3.2m worth of wine last year. Now the US wants a piece of that action

Côte d'Ivoire is sub Sahara Africa's biggest importer of wine, says the US department of agriculture, and it is time American companies take advantage of the market.




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The Efficacy of Digital Media Resources in Improving Children’s Ability to Use Informational Text: An Evaluation of Molly of Denali From PBS KIDS

Informational text — resources whose purpose is to inform — is essential to daily life and fundamental to literacy. Unfortunately, young children typically have limited exposure to informational text. Two 9-week randomized controlled trials with 263 first-grade children from low-income communities examined whether free educational videos and digital games from the PBS KIDS show “Molly of Denali” supported children’s ability to use informational text to answer real-world questions. Study 1 found significant positive intervention impacts on child outcomes; Study 2 replicated these findings.




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agilePHM – a new open source product for rapid prototyping of PHM analytics

agilePHM We are launching a new product called agilePHM In Industrial IoT, I have been working with PHM  (Prognostics and Health Management) for a while and it is a well known discipline Prognostics and Health management(PHM)  is an engineering discipline focused on predicting the time at which a system or a component will no longer perform its intended [...]





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Meme Coins Are Soaring as Pepe Unchained Layer 2 ICO Raises $27.5 Million

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.




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News24 Business | Microsoft beefs-up its AI assistant with voice, vision

Microsoft on Tuesday doubled down on deploying artificial intelligence to consumers, releasing an updated version of its Copilot chatbot that can hold voice conversations and interpret images.




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News24 Business | South African AI body calls for LinkedIn probe over alleged local user data violations

The South African Artificial Intelligence Association wants LinkedIn to be investigated, as it claims the social networking platforms new data use practice violates local personal information protection law.




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News24 Business | TikTok billionaire becomes China's richest person

ByteDance founder Zhang Yiming is China's richest person, with personal wealth of $49.3 billion (R872 billion), an annual rich list showed on Tuesday, although counterparts in real estate and renewables have fared less well.




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News24 | Patients lie on the floor at Uitenhage hospital - some with serious injuries

Patients lie on the floor at Uitenhage Provincial Hospital in Kariega, some with drips in their veins.




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News24 | SA Jewish Board of Deputies approaches Equality Court with social media hate speech complaint

The Cape South African Jewish Board of Deputies has asked the Equality Court in Cape Town to declare politician Mehmet Vefa Dag's social media posts about about Jewish people hate speech.




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News24 | Fraser's Phala Phala claims something from a movie, but baseless, says Ramaphosa's lawyer

President Cyril Ramaphosa's lawyers say former spy boss Arthur Fraser's claims about the Phala Phala break-in are like something from a movie - but are founded on nothing more than baseless speculation.




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News24 | Heat attack: 2024 is world's hottest year, and likely to leave South Africans sweating this summer

The World Meteorological Organisation (WMO) has raised the alarm over climate change, reporting 2024 is the world's hottest year yet.




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News24 | 'Explainer-in-chief': Rasool aims to amplify SA's voice globally in second stint as ambassador in US

When Ebrahim Rasool returns to Washington in December as South Africa's ambassador, one of his primary goals is to reposition Pretoria as a "moral superpower"





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Software Architecture in an AI World

Like almost any question about AI, “How does AI impact software architecture?” has two sides to it: how AI changes the practice of software architecture and how AI changes the things we architect. These questions are coupled; one can’t really be discussed without the other. But to jump to the conclusion, we can say that […]




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Trump lies, sows division, and wastes recovery resources as Americans suffer

Adjudicated rapist and convicted felon Donald Trump chose to politicize the Federal response to Hurricane Helene, demonstrating little concern about the actual devastation.

Responsible leaders who care about the people they govern do not leap into every photo opportunity they can find. — Read the rest

The post Trump lies, sows division, and wastes recovery resources as Americans suffer appeared first on Boing Boing.




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Music really does sound better when you're high, scientists report

Neuroscientists have confirmed what every stoner already knows: music sounds better when you're high on weed. In a paper titled "Exploring the interaction between cannabis, hearing, and music," researchers from Toronto Metropolitan University reported results from a study in which participants "reported significantly greater hearing sensitivity and levels of state absorption while high compared to sober." — Read the rest

The post Music really does sound better when you're high, scientists report appeared first on Boing Boing.




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Enterprise Software: Saas vs. the Big Three

Forbes.com published an article by Dan Woods where he describes a battle between the traditional enterprise software providers (Microsoft, SAP, and Oracle) and Saas providers like Salesforce.com and NetSuite.

According to Woods, SaaS applications are easier to use because they offer streamlined interfaces that are modeled after successful web consumer sites like Amazon.com, Yahoo!, eBay, Google, etc. These SaaS interfaces were designed to be easily configurable.

Traditional enterprise software is not as easy to use because user interfaces are often created before it is known exactly how the software would be used. Customization to the user interface is often done at installation by systems integrators who do not have any actual user behavior on which to base their customizations.


The Big Three are well aware of the usability gap between their products and SaaS software, but it is unclear how to solve the problem. Oracle emphasizes Fusion as an integration platform. SAP recently announced an experiment called Blue Ruby that is attempting to adapt Ruby on Rails as a user interface and programming technology for its applications. But is it possible to affordably automate a business starting with a configurable application platform that must be adapted to the specific user interfaces and business processes in a company? The SaaS model starts with a usable interface and a working automation of common processes, and then has the configuration proceed from there. The hosted nature of SaaS removes the deployment barriers.



IVT software is the only webcasting and digital asset management applications available both as a SaaS and as a behind-the-firewall installation. With webcasting software, the divide has included the question: should there be proprietary hardware or should the solution be software-only.

IVT falls on the software-only side, believing that "black box" proprietary hardware is not scalable and is prone to obsolescence.

IVT software on a SaaS basis works with the network infrastructure that already exists, which is one of the competitive advantages we take to the enterprise video battle.




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IVT Raises $5.5 Million for Webcasting Software

As the article appeared in TechCrunch...

IVT, a company that produces enterprise-friendly webcasting software, has raised $5.5 million in Series B funding from Syncom Venture Partners with Barshop Ventures, Monitor Ventures and Tudor Ventures participating in the investment round. IVT raised $3 million in Series A funding in 2006.
IVT’s SaaS offering not only helps power webcasts, but also converts multimedia files, such as slideshows, into viewable videos for the web. IVT also offers a YouTube-like hosting and social media site for companies to disseminate videos and webcasts. And the startup has a number of prominent companies that use its webcasting software including Oracle, Dow Chemical, IBM and NEC.




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IVT Takes Webcasting Software Platform to the Cloud

IVT, Inc. has moved its industry-leading MediaPlatform webcasting software platform to the cloud. With MediaPlatform increasingly being used in large-scale webcasts by media producers, as well as Fortune 500 clients, the company is elevating its delivery capacity through a partnership with a tier-1 cloud infrastructure provider.

“Our mission has always been to deliver the best quality of service and enable our clients to produce webcasts at literally any audience size without concern for infrastructure,” said Jim McGovern, Chief Executive Officer of IVT. “Now that cloud-based platforms are gaining widespread acceptance across the IT world, we can give our clients the benefit of switching capacity on and off when required.”

This is not the first time IVT has been ahead of the technology curve in the webcasting industry. The company pioneered the concept of offering webcasting software on a Software-as-a-Service (SaaS) basis with MediaPlatform. With MediaPlatform in the cloud, IVT enables its clients to benefit from what is rapidly emerging as the new paradigm for corporate computing.

In the cloud, MediaPlatform’s web services architecture can more readily serve diverse client needs by integrating with a range of enterprise systems, both cloud-based and on-premises.
The cloud, an approach to computing that places servers and infrastructure in remote, abstracted datacenters, is ideal for webcasting, which is known for unpredictable spikes in system load. By working with a tier-1 cloud infrastructure provider, IVT gains virtually unlimited capacity and world-class security, reliability, redundancy, failover, and load management.

IVT will continue to support the numerous on-premises installations of its software, including major deployments at global enterprises. IVT prides itself on offering its clients the choice between hosted and on-premises options.




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Interactive Media Strategies believes Microsoft could win big with Skype

Interactive Media Strategies (IMS) is a market research firm that follows streaming media. They discuss the news of Microsoft’s $8.5 billion acquisition of Skype, and the prospects for Skype to emerge as a viable platform for business video communications. 

Their research compares usage levels for a range of social media and communications applications, including Skype, YouTube and Facebook. Here is a link to the video.

They report that personal use of Facebook and YouTube is relatively high but that has not yet translated into comparable levels of corporate use. They believe this raises the question of whether YouTube and Facebook will be able to outgrow their focus on the consumer side of the business to compete in the enterprise market.

Usage levels for Skype are significantly lower overall, but Skype’s penetration in business communications is higher than they see for other communications apps online among young users most likely to experiment with emerging technologies.

IMS puts forth the opinion that if Microsoft could make it easier for technology laggards to embrace Skype - i.e. integrate Skype with the Microsoft Office suite - then Skype could achieve significant enterprise adoption.




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Unhinged Liberal Women Cry On Social Media Over Trump’s Victory And Falsely Claim They’ve Lost All Their Rights

The following article, Unhinged Liberal Women Cry On Social Media Over Trump’s Victory And Falsely Claim They’ve Lost All Their Rights, was first published on Conservative Firing Line.

(Natural News) Liberals have been working hard to portray Trump as a misogynist, and it worked on a lot of women – with some of them buying into the false narrative that he will work against women so wholeheartedly that they are now having very public meltdowns over his victory. Revolver put together some of the …

Continue reading Unhinged Liberal Women Cry On Social Media Over Trump’s Victory And Falsely Claim They’ve Lost All Their Rights ...




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The Poisoning of America

The following article, The Poisoning of America, was first published on Conservative Firing Line.

America has spoken: Donald J. Trump won a landslide victory on November 5. However, the butthurt leftists are doing what they did last time: throwing a hissy fit. The difference this time is that the victory was so strong that all they have is to make ridiculous claims that are in fact, the poisoning of …

Continue reading The Poisoning of America ...




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Resolved: Stop Blaming the Pancake

In a classic bit from an early Seinfeld, Jerry and Elaine are at the airport, trying to pick up the rental car that Jerry had reserved. As usual, things go poorly and get awkward fast:

Seinfeld - "Reservations"

JERRY: I don't understand...I made a reservation. Do you have my reservation?
AGENT: Yes, we do. Unfortunately, we ran out of cars.
JERRY: But, the reservation keeps the car here. That's why you have the reservation.
AGENT: I know why we have reservations.
JERRY: I don't think you do. If you did, I'd have a car. See, you know how to take the reservation--you just don't know how to hold the reservation. And, that's really the most important part of the reservation...the holding. Anybody can just TAKE them. [grabs chaotically at air]

And, how weirdly similar is that to our conflicted relationship with New Year's resolutions?

In Seinfeldspeak?

See, you know how to make the resolution, you just don't know how to keep the resolution. And, that's really the most important part of the resolution...the keeping. Anybody can just MAKE them!

Oversimplified? Probably.

But, ask yourself. Why this? And, why now? Or, why again?

Welcome to Resolvers Anonymous: I'm 'Merlin M.'

A few years ago, I shared a handful of stories on the failures that have led to my own cynicism about the usefulness of life-inverting resolutions. Because, yeah, I've historically been a big resolver.

Here's what I said when I first suggested favoring "Fresh Starts and Modest Changes" over reinventions:

Download MP3 of "Fresh Starts & Modest Changes"

Five years on, I think I probably feel even more strongly about this.

Partly because I've watched and read and heard the cyclical lamentations of folks who decided to use superficial totems (like new calendars) as an ad hoc coach and prime mover. And, partly because, in my capacity as a makebelieve productivity expert, I continue to see how self-defeating it is to pretend that past can ever be less than prologue--that we can each ignore yesterday's weather if we really wish hard enough for a sun-drenched day at the beach.

It simply doesn't work.

Companies that think they'll be Google for buying bagels. Writers who think they'll get published if they order a new pen. Obese people who think they'll become marathon runners if they pick up some new running shoes. And, regular old people with good hearts who continue to confuse new lives with new clothes.

Has this worked before? Can you look back on a proud legacy of successful New Year's resolutions that would suggest you're making serious progress by repeatedly making a list about fundamental life changes while slamming prosecco and wearing a pointy paper hat?

My bet is that most people who are seeing the kind of change and growth and improvement that sticks tend to avoid these sorts of dramatic, geometric attempts to leap blindly toward the mountain of perfection.

I'll go further and say that the repeated compulsion to resolve and resolve and resolve is actually a terrific marker that you're not really ready to change anything in a grownup and sustainable way. You probably just want another magic wand.

Otherwise you'd already be doing the things you've resolved to do. You'd already be living those changes. And, you'd already be seeing actual improvements rather than repeatedly making lists of all the ways you hope your annual hajj to the self-improvement genie will fix you.

Then, of course, we make things way worse by blaming everything on our pancakes.

Regarding "The First Pancake Problem"

Anyone who's ever made America's favorite round and flat breakfast food is familiar with the phenomenon of The First Pancake.

No matter how good a cook you are, and no matter how hard you try, the first pancake of the batch always sucks.

It comes out burnt or undercooked or weirdly shaped or just oddly inedible and aesthetically displeasing. Just ask your kids.

At least compared to your normal pancake--and definitely compared to the far superior second and subsequent pancakes that make the cut and get promoted to the pile destined for the breakfast table--the first one's always a disaster.

I'll leave it to the physicists and foodies in the gallery to develop a unified field theory on exactly why our pancake problem crops up with such unerring dependability. But I will share an orthogonal theory: you will be a way happier and more successful cook if you just accept that your first pancake is and always will be a universally flukey mess.

But, that shouldn't mean you never make another pancake.

So Loud. Then, So Quiet.

I offer all of this because today is January 7th, gang. And, for the past week, all over the web, legions of well-intentioned and seemingly strong-willed humans have been declaring their resolved intention to make this a year of more and better metaphorical pancakes.

And, like clockwork--usually around today or maybe tomorrow--a huge cohort of those cooks will begin to abandon their resolve and go back to thinking all their pancakes have to suck. Just because that first one failed.

And, as is the case every year, online and off, there won't be nearly as many breathless updates to properly bookend how poorly our annual ritual of aspirational change has fared. Which is instructive.

Not because new year's resolutions are a universally bad idea. And, not because Change is Bad. And, not because we should be embarrassed about occasionally falling short of our own (frequently unreasonable) aspirations.

I suspect we tout the resolution, but whisper the failure because we blame the cook. Or, worse, fingers point toward the pancake. Instead of just admitting that the resolution itself was simply unrealistic or fundamentally foreign.

And, that's a shame.

Remember, there's no "I" in "unreasonable"

Granted, I'm merely re-repeating a point I've struggled to make (to both others and myself) for years now. But, it will bear repeating every January in perpetuity.

Resist the urge to pin the fate of things you really care about to anything that's not truly yourself. The "yourself" who has a real life with complicated demands. The "yourself" who's going to face a hard slog trying to fold a new life out of a fresh calendar.

Calendars are just paper and staples. They can't make you care. And they can't help you spin around like Diana Prince, and instantly turn into Wonder Woman. Especially, if you're not already a hot and magical Amazon princess.

First, be reasonable. Don't set yourself up for failure by demanding things that you've never come close to achieving before. I realize this is antithetical to most self-improvement bullshit, but that's exactly the point. If you were already a viking, you wouldn't need to build a big boat. Start with where you are right now. Not with where you wish you'd been.

Also, accept that the first pancake will always suck. Hell, if you've never picked up a spatula before, be cool with the fact that your first hundred pancakes might suck. This is, as I've said, huge. Failure is the sound of beginning to suck a little less.

And, finally, also be clear about the sanity of the motivations underlying your expectations--step back to observe what's truly broken, derive a picture of incremental success that seems do-able, and really resolve to do whatever you can realistically do to actually get better. Rather than "something something I suddenly become all different."

At this point, you have logistical options for both execution and troubleshooting:

  • Make a modest plan that you can envision actually doing without upending your real life;
  • Build more sturdy scaffolding for sticking with whatever plan you've chosen;
  • Make a practice of learning to not mind the duds--including those messed-up first pancakes;
  • Or--seriously?--just accept that you never really cared that much about making breakfast in the first place. Care is not optional.

Otherwise, really, you'd never need to resolve to do anything. You'd already just be cooking a lot. Instead of being all mad and depressed about not cooking.

But, please. All I really ask of you. Don't blame the pancake. It's not really the pancake's fault.

Like me, the pancake just wants you to be happy. This and every other new year.


Resolved: Stop Blaming the Pancake” was written by Merlin Mann for 43Folders.com and was originally posted on January 07, 2011. Except as noted, it's ©2010 Merlin Mann and licensed for reuse under CC BY-NC-ND 3.0. "Why a footer?"




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No One Needs Permission to Be Awesome

Steve Jobs' 2005 Stanford Commencement Address

No one wants to die, even people who want to go to Heaven don't want to die to get there.

And yet, death is the destination we all share. No one has ever escaped it.

And that is as it should be. Because death is very likely the single best invention of life.

It's life's change agent; it clears out the old to make way for the new.

[…]

Your time is limited, so don't waste it living someone else's life. Don't be trapped by dogma, which is living with the results of other people's thinking. Don't let the noise of others' opinions drown out your own inner voice, heart and intuition. They somehow already know what you truly want to become. Everything else is secondary.

None of us should ever have to face death to accept the inflexible and, too-often, novel sense of scarcity that it introduces.

In fact, it'd be great if we could each skip needing outside permission to be awesome by not waiting until the universe starts tapping its watch.

A simple start would involve each of us learning to care just a little more about a handful of things that simply aren't allowed to leave with us--whether today, tomorrow, or whenever. Because, I really believe a lot of nice things would start to happen if we also stopped waiting to care. A whole lot of nice things.

If that sounds like fancy incense for hippies and children, perhaps in a way that seems frankly un-doable for someone as practical and important and immortal as yourself, then go face death.

Go get cancer. Or, go get crushed by a horse Or, go get hit by a van. Or, go get separated from everything you ever loved forever.

Then, wonder no longer whether caring about the modest bit of time you have here is only for fancy people and the terminally-ill.

Because, the sooner you care, the better you'll make. The better you'll do. And the better you'll live.

Please don't wait. The universe won't.

No One Needs Permission to Be Awesome” was written by Merlin Mann for 43Folders.com and was originally posted on January 17, 2011. Except as noted, it's ©2010 Merlin Mann and licensed for reuse under CC BY-NC-ND 3.0. "Why a footer?"










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A.F. Branco Cartoon – Toon Soon?

A.F. Branco Cartoon – Some say Gov. Walz is celebrating a bit too early on winning the 2024 election despite..




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Another House Speaker Battle? Mike Johnson's Position May Be at Risk as Conservative Anger Heats Up

Now that there is a Republican majority in the next Congress, it’s time for the party to bare its internal fault lines. That is likely to take place Wednesday, according […]

The post Another House Speaker Battle? Mike Johnson's Position May Be at Risk as Conservative Anger Heats Up appeared first on The Western Journal.




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Sport | Khanyiso Tshwaku | Markram's T20 run drought no laughing matter as leadership crown weighs heavy

As captain, Aiden Markram is allowed a long rope from a wonky form perspective, but how long can that rope be as the run river continues to shrivel, asks Khanyiso Tshwaku.




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Sport | Makgopa's rise evidence of Broos' Bafana impact: 'You don't want to disappoint such a person'

Evidence Makgopa wore a sheepish smile when Bafana Bafana coach Hugo Broos showered him with praise before literally patting the forward on the back, making him blush at Dobsonville Stadium.




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Egyptian Government Television Episode About Farahat’s Book

Cairo, Egypt Oct. 28, 2022 On Egyptian TV show, “Headlines,” Dr. Hossam Farouk dedicated an episode to discussing national and international coverage of the Secret Apparatus: The Muslim Brotherhood’s Industry of Death. It was a great honor having the book featured on this great show.





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The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2 [Computational Biology]

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.




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Member’s question time: Is Russia losing the South Caucasus?

Member’s question time: Is Russia losing the South Caucasus? 22 October 2024 — 1:00PM TO 1:30PM Anonymous (not verified) Online

Join us and ask Chatham House Senior Research Fellow, Natalie Sabanadze anything about the situation in the Caucasus. Submit your questions in advance.

Whilst Russia focuses on its illegal invasion of Ukraine, the situation at its southern border is evolving. Relations between the three states in the South Caucasus and Moscow have never been easy as Russia tried to maintain its dominance by leveraging vulnerabilities, playing one side against another to keep conflicts simmering and even engaging in open military aggression.  Although the violence seen in the 1990s and early 2000s has abated, the war in Ukraine has had an indirect impact on the region, bringing a change to the status quo.

Russia abandoned its long-standing support for Armenia, allowing for the collapse of Nagorny-Karabakh and the restoration of the territorial integrity of Azerbaijan with the backing of Turkey. As a result, Azerbaijan has emerged as a dominant regional player with Baku recently declaring its interest to join BRICS.  Turkey’s influence has grown, while Armenia frustrated by Russia’s change of heart has been turning cautiously towards the EU and the US.

In Georgia, meanwhile, the ruling party has been consolidating its grasp on power, rolling back democratic reforms and pivoting away from the West. Georgia’s long-awaited European integration process has been suspended, following the adoption of the Russian-style foreign agents legislation.

Join us as our Senior Research Fellow in the Russia and Eurasia Programme answers your questions in this quick-fire session assessing the extent to which the Russian influence has changed since the start of the invasion of Ukraine and who is there to fill the vacuum; how geopolitical contestation in the region is going to impact aspirations of Armenia, Azerbaijan and Georgia; and much more.

Submit your questions to Natalie Sabanadze in advance of the event. Your questions will drive the conversation.




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Fluorescence assay for simultaneous quantification of CFTR ion-channel function and plasma membrane proximity [Methods and Resources]

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.




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Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function [Molecular Bases of 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.




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Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work

Water, Ecosystems and Energy in South Asia: Making Cross-Border Collaboration Work Research paper sysadmin 29 June 2016

A new paper sets out the factors that have made previous cross-border projects in South Asia successful, arguing that cooperation around water is feasible despite the region’s political differences and economic assymetries.

Indian people walk in the Ganga riverbed in Allahabad on 1 September 2015. Photo: Getty images.

  • The countries of South Asia share some of the world’s major river basins – the Ganga (or Ganges), the Brahmaputra and the Indus. These rivers and their tributaries flow through seven countries, support more than 1 billion people, irrigate millions of hectares of land and are of cultural importance to many of those who rely on them.
  • River management presents common challenges across the region. These include physical factors such as droughts, flooding, cyclones and climate change, as well political and institutional factors impeding the development of solutions and policies to improve resource management and reduce vulnerability. Water is increasingly seen as a source of competition, with population growth, industrialization and urbanization exacerbating the pressures on supply.
  • Although South Asian examples of regional cooperation in general are limited, there is a clear positive trend. In areas such as disaster response and cross-border power trading, regional and bilateral engagement is beginning to take place. Multilateral official arrangements exist for trade and other economic issues, but there is none on water or ecosystems. However, as the benefits from cooperation become proven, its desirability is likely to gradually enter mainstream policy thinking on water issues.
  • This research paper sets out the factors that have enabled cooperation, and the processes adopted, in previous successful cross-border projects. It focuses on four categories of cooperation: development of early-warning systems for natural disasters, in particular floods; protection of cross-border ecosystems; sharing of learning, through the showcasing of innovative approaches in one country that can be adopted by others; and power trading, in particular the development of hydropower in Bhutan and its export to India.
  • The paper argues that cooperation around water in South Asia is feasible despite political differences and economic asymmetries. Different forms of collective action, and common understanding of both the threats and the shared benefits from cooperation, are required to foster more partnerships within the river basin states.




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Policy for Recovery in Africa: Rethinking Energy Solutions for Universal Electricity Access

Policy for Recovery in Africa: Rethinking Energy Solutions for Universal Electricity Access 10 December 2020 — 5:00PM TO 6:00PM Anonymous (not verified) 20 November 2020 Online

Approximately three quarters of Africa’s population do not have access to clean cooking fuel and face costs to their health. Speakers explore policy opportunities to bridge this gap, the key barriers that remain and the transformative potential of energy transition in delivering sustainable access for all.

Speakers explore policy opportunities to bridge the energy access gap, the key barriers that remain and the transformative potential of energy transition in delivering sustainable access for all.

African countries face an uphill battle as they confront the shocks of the coronavirus pandemic, seeking recovery in the context of global socio-economic difficulty and fragmented geopolitics.

With deficits in terms of governance, public health systems, social protection, and basic service delivery presenting challenges even before the outbreak, careful analysis and creative evidence-based policy solutions, as well as emphasis on implementation, will be crucial if Africa is to progress towards the SDGs and Agenda 2063.

The Policy for Recovery in Africa series brings together expert speakers and decision makers to examine and exchange on key challenges, potential solutions, and approaches for implementation.

The energy access gap in Africa presents one of the most serious obstacles to the long-term pandemic recovery effort, with almost half of the continent’s population estimated to still lack access to electricity, creating a negative annual GDP impact estimated to be over 25 billion USD.