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US bans flights to Haiti for a month after gunfire hit Spirit airliner

One flight attendant was injured when gang gunfire struck the Spirit Airlines flight to Port-au-Prince on Monday




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Power Shortage To Hit 40% of AI Data Centres by 2027, Gartner Warns

40% of AI data centers will face operational constraints due to power shortages by 2027 as AI drives unprecedented energy consumption, research firm Gartner said on Tuesday. Data center power requirements for AI-optimized servers are projected to reach 500 terawatt-hours annually by 2027, more than double 2023 levels, as companies rapidly expand facilities to handle large language model training and implementation. The surge in power demand will outpace utility providers' ability to expand capacity, Gartner analyst Bob Johnson said, leading to higher electricity costs that will cascade through the AI industry. Some operators are already seeking direct agreements with power producers to secure guaranteed supply.

Read more of this story at Slashdot.




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Prominent law professor blames Harris loss on ‘white supremacy’ and ‘toxic masculinity’

In the 2024 election, Donald Trump easily carried many predominantly Hispanic rural areas like Hidalgo County, Texas, and some mostly non-white precincts, such as mostly Asian areas of Brooklyn. As journalist Josh Kraushaar noted, “Trump carried PASSAIC County, New Jersey. Majority/Hispanic electorate and home to a sizable Orthodox Jewish constituency. Was a Dem stronghold for […]

The post Prominent law professor blames Harris loss on ‘white supremacy’ and ‘toxic masculinity’ appeared first on Liberty Unyielding.




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'We are not military - why are we being hit?'

In the Lebanese city of Nabatieh, Orla Guerin meets hospital patients and medics vowing to stay despite Israeli strikes.




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Watch: Barcelona airport and highways hit by flooding

Video shows a flooded terminal inside El Prat airport and partially submerged cars on a highway.




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Watch: Cars washed away as new flash floods hit Spain

There were no immediate reports of casualties after heavy rain on Thursday.





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News24 | Businessman Alix Didier Fils-Aime takes over as PM of crisis-hit Haiti

Businessman Alix Didier Fils-Aime was sworn in as Haiti's new prime minister on Monday as a gun attack on a passenger jet at the capital's airport underscored the utter breakdown in law and order in the Caribbean country.





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News24 Business | Huawei 'super fans' annoyed at lack of supply as pricey phone hits China stores

Many fans of Huawei on Friday were disappointed that its much-anticipated phone, Mate XT - more than twice the price of the iPhone 16 Pro Max - was not available for walk-in customers.




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News24 Business | Internet Archive, Wayback Machine hit by 'catastrophic' cyberattack, data breach

The Internet Archive, an online repository of web pages, was offline Thursday after its founder confirmed a major cyberattack that exposed the data of millions of users and left the site defaced.




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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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Do you like party games and music history? Try HITSTER

I recently attended a weekend-long birthday getaway for an old college friend, and as soon as I arrived, he pulled out a box and said, "You have to play this game."

And he was right.

Hitster describes itself as a Music Party Board Game, and that's accurate. — Read the rest

The post Do you like party games and music history? Try HITSTER appeared first on Boing Boing.




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“Distraction,” Simplicity, and Running Toward Shitstorms

It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience.

—Albert Einstein, “On the Method of Theoretical Physics” (1934)

Context: Last week, I pinched off one of my typically woolly emails in response to an acquaintance whom I admire. He’s a swell guy who makes things I love, and he'd written, in part, to express concern that my recent Swift impersonation had been directed explicitly at something he'd made. Which, of course, it hadn’t—but which, as I'll try to discuss here, strikes me as irrelevant.

To paraphrase Bogie, I played it for him, so now I suppose I might as well play it for you.


(n.b.: Excerpted, redacted, munged, and heavily expanded from my original email)

There are at least a couple things that mean a lot to me that I'm still just not very good at.

  • Make nuanced points in whatever way they need to be made; even if that ends up seeming “un-nuanced”
  • Never explain yourself.

I want to break both these self-imposed rules privately with you here. [Editor’s Note: Um.] Because, I hope to nuance the shit out of some fairly un-nuanced points. And, to do that, I'll also (reluctantly) need to explain myself. But, here goes.

First [regarding my goofing on “distraction-free writing environments”] I think there are some GIANT distinctions at play here that a lot of folks may not find nearly as obvious as I do:

  1. Tool Mastery vs. Productivity Pr0n – Finding and learning the right tools for your work vs solely dicking around with the options for those tools is just so important, but also so different. And, admittedly, it’s almost impossible to contrast those differences in terms of hard & fast rules that could be true for all people in all situations. But, that doesn’t make the difference any less qualitatively special or real.

    Similarly…
  2. Self-Help Vs. “Self”–“Help” – Solving the problem that caused the problem that caused the problem that caused the symptom we eventually noticed. Huge. Arguably, peerless.

    • Viz.: How many of us ignore the actual cause of our problem in favor of just reading dozens of blog posts about how to “turbocharge” its most superficial symptoms? Sick.
  3. Focus & Play – Yes, focusing on important work is, as Ford used to say, Job 1. But, that focus benefits when we maintain the durable and unapologetic sense of play that affords true creativity and fosters an emergence of context and connection that’s usually killed by stress. BUT.

    • Again, what conceivable “rule” could ever serve to immutably declare that “THIS goofing-off is critical for hippocampal plasticity” vs. “THAT goofing-off is just dumb, distracting bullshit?”
    • Impossible. Because drawing those kinds of distinctions is one of our most important day-to-day responsibilities. Decisions are hard, and there’s no app or alarm gadget that can change that.

      • Although, they certainly can help mask the depth of the underlying problem that made them seem so—what’s the parlance?—“indispensable”.
      • Think: Elmo Band-Aids for that unsightly pancreatic tumor.
  4. Reducing Distraction through Care (Rather than braces, armatures, and puppet strings). Removing interruptions and external distractions that harm your work or life? Great. Counting on your distraction-removal tool to supplement your non-existent motivation to do work that will never get done anyway? Pathetic.

    • Frankly, this is a big reason I'm so galled when anyone touts their tool/product/service as being the poor, misunderstood artist’s new miracle medicine—rather than just admitting they've made a slightly different spoon.
    • Because, let’s be honest: although most of us have plenty of perfectly serviceable spoons, everybody knows collecting cutlery is way more fun than using it to swallow yucky medicine.
  5. Using a System Vs. Becoming a System. Having a system or process for getting work done vs. making the iteration of that system or process a replacement for the work. This is just…wow…big.

    But, maybe most importantly to me…

  6. Embracing the Impossibles. Getting past these or any other intellectual koans by simply accepting life’s innumerable and unresolvable paradoxes, hypocrisies, and impossibilities as God-given gifts of creative constraint. Rather than, say, a mimeographed page of long division problems that must be solved for a whole number, n.

    • I just can’t ever get away from this one. For me, it’s what everything inevitably comes back to.
    • The very definition of our jobs is to solve the right problem at the right level for the right reason—based on a combination of the best info we have for now and a clear-eyed dedication to never pushing an unnecessary rock up an avoidable hill.
    • YET, we keep force-feeding the monster that tells us to fiddle and fart and blame the Big Cruel World whenever we face work that might threaten our fragile personal mythology.

      • “Sigh. I wish I could finally start writing My Novel….Ooooooh, if only I had a slightly nicer pen…and Zeus loved me more….”

All that stuff? That there’s a complex set of ideas to talk about for many complex reasons—not least of which being how many people either despise or (try to) deny the unavoidable impact of ol' number six.

But, here’s the thing: as much as saying so pisses anybody off, I think the topics we're NOT talking about whenever we disappear into Talmudic scholarship about “full-screen mode” or “minimalist desks” or whatever constitutes a “zen habit”—those shunned topics are precisely the things that I believe are most mind-blowingly critical to our real-world happiness as humans.

In fact, I believe that to such a degree that helping provide a voice for those unpopular topics that can be heard over the din is now (what passes for) my career. I really believe these deeper ideas are worth socializing on any number of levels and in many media. Even when it’s inconvenient and slightly disrespectful of someone’s business model.

So, that’s what I try to do. I talk about these things. Seldom by careful design. Often poorly. But, always because they each mean an awful lot to me.

[…]

But, no matter how I end up saying whatever the hell I say, I believe in saying it not simply to be liked or followed or revered as a “nice guy” who pushes out shit-tons of whatever to “help people.”

Because, believe me, friend, a great many of those apparently “nice guys” swarming around the web “helping people” these days are ass-fucking their audience for nickels and calling it a complimentary colonoscopy. And, while I absolutely think that in itself is empirically wrong, I also think it’s just as important to say that it’s wrong. Sometimes, True Things need to be said.

Which in this instance amounts to saying, a) selling people a prettier way to kinda almost but not really write is not, in the canonical sense, “nice”—but, far worse, b) leaving your starry-eyed customers with the nauseatingly misguided impression that their “distraction” originates from anyplace but their own busted-ass brain is really not “helping.” Not on any level. It is, literally, harmful.

“Helping” a junkie become more efficient at keeping his syringe loaded is hardly “nice.”

It’s the opposite of nice. And, it’s the opposite of helpful. These are my True Things.

And, to me, saying your True Things also means not watering down the message you care about in order to render it incapable of even conceivably hurting someone’s feelings—or of even conceivably losing you even one teeny-tiny slice of that precious “market share.”

Well, that’s the price, and I'm fine paying it—best money I've ever spent.

But, it also means trusting your audience by letting each of them decide to add water only as they choose to—by never corrupting the actual concentrate in a way that might make it less useful to the smartest or most eager 5% of people who'd like to try using it undiluted. Because, at that point, you're not only abandoning the coolest people you have the honor of serving—you risk becoming a charlatan.

And, that’s precisely what you become when you start to iteratively inbreed the kind of fucktard audience for whom daily buffets of weak swill and beige assurance are life’s most gratifying reward.

Sure. Those poor bastards may never end up using any of that watery information to do anything more ambitious than turbocharging their most regrettable symptoms. But, who’s the last person in the universe who’s going to grab them by the ears and tell them to get back to work? Exactly—that same “nice guy” whose livelihood now depends on keeping infantalized strangers addicted to his “help.”

Holy shit—no way could I ever live with that. It’s so wrong, it’s not even right. ESC, ESC, ESC!

[…]

Okay. So anyhow, there’s a really long-winded, overly generous, and extremely pompous way of trying to say I don’t know how to do what I do except how I do it. But, I do genuinely feel awful when innocent people feel they have been publicly humiliated or berated simply because I'm some dick who hates people.

Which has to be my favorite irony of all.

When I was a kid, I thought my Mom was “mean” not to let me play in traffic on busy Galbraith Road. Today, I'm not simply grateful that she had the strength and resolve to be so “mean”—I actually can’t imagine how sad it would be to not have people in your life who care enough about your long-term welfare to tell you to stop fucking around in traffic. To where you eventually might start even seeking 12x-daily safety hacks from some of the very same drivers whose recklessness may eventually kill you. Wow.

[…]

Admitting when life is complicated or things aren’t shiny and happy all the time strikes me as a wonderfully sane and adult way to conduct one’s life. That there are so many folks offended by even the existence of this anarchic idea is not a problem I can solve.

No more than I can wish useless email away or pray hard enough that it never rains on anyone’s leaky roof. All out of scope.

And, then, I jizzed on at length about how much I admire the recipient’s work. Which I do.


Good work doesn’t need a cookie

I may admire your work, too. Especially if you care a lot about that work and don’t overly sweat peoples' opinions of it. Most definitely including my own.

For these purposes, it doesn’t really matter whether we're friends and, honestly, it doesn’t even matter whether I love, use, or agree with everything you do, say, or make in a given day.

It doesn’t matter because good work doesn’t need me to love it. Like tornadoes and cold sores, good work happens with total disregard to whether I'm “into it.”

But, conversely, let’s stipulate that the points-of-view undergirding our opinions—again, including mine—will and should survive either agreement or lack of agreement with equivalently effortless ease. Because, like really good work, a really good point-of-view doesn’t require another person’s benediction.

Guess we'll have to disagree to agree

Now, to be only vaguely clearer here, I'm not posting this circuitous ego dump in the service of altering your opinion of either me, my friend, his work, or practically anything else for that matter.

But, I would love it if we could all be more okay with the fact that real life means that we do each have a different, sometimes incongruous, and often totally incompatible point-of-view. Yes. Even you have a point-of-view that someone despises. Ready to change it now? Jesus, I sure hope not.

Then, to be only slightly more clear, I'm also not advocating for that fakey brand of web-based kum ba ya that gets trotted out alternately as “tolerance” or “inclusion” or some styrofoam miniature of “civility.”

I'm absolutely not against all of those things when authentically practiced, but I'm also really skeptical of the well-branded peacemakers who are forever appointing themselves the Internet’s “Now-Now-Let’s-All-Pretend-We're-Just-Saying-the-Same-Useless-Thing-Here” den mothers.

Because we're not all saying the same things. Not at all.

And, it infantalizes some important conversations when we tacitly demand that any instance of honest disagreement be immediately horseshat into a photo opp where some thought leader gets to hoist everyone’s hands in the air like he’s fucking Jimmy Carter.

Nope. Not saying that.

Who will you really rely on?

What I AM saying is that alllllll this seemingly unrelated stuff is absolutely related—that the pattern of not relying on other people for anything you really care about is arguably the great-grandaddy of every useful productivity, creativity, or self-help pattern.

Where’s this matter? Pretty much everywhere you have any sort of stake:

  • Don’t rely on other people to remove your totally fake “distractions.”
  • Don’t rely on other people to pat your beret, re-tie your cravat, and make you a nice cocoa whenever that mean man on the internet points out that your “distractions” are totally fake. (Which they are)
  • Don’t rely on other people to tell you when or whether you have enough information.
  • Don’t rely on other people to define your job.
  • Don’t rely on other people to “design your lifestyle.”
  • Don’t rely on other people to decide when your opinions are acceptable.
  • Don’t rely on other people to tell you when you're allowed to be awesome.
  • Don’t rely on other people to make you care.
  • Don’t even rely on other people to tell you what you should or shouldn’t rely on.

Yes. I went there.

Because that’s the point. These hypocrisies, paradoxes, and ambiguities that people get so wound up about—that many of us are constantly (impotently) trying to resolve—cannot be resolved.

Because, yeah: all of these harrowingly unsolvable problems are immune to new notebooks and less-distracting applications and shinier systems and “nicer” self-“help” and pretty much anything else that is not, specifically, you walking straight into the angriest and least convenient shitstorm you can find and getting your ass kicked until the storm gets bored with kicking it.

Then, you find an even angrier storm. Then, another. And, so on.

“Get the fuck off of my obstacle, Private Pyle!”

Doing that annoying hard stuff is how you grow, get better, and learn what real help looks like. Even if that’s not the answer you wanted to hear. You get better by getting your ass out of your RSS reader and fucking making things until they suck less. Not by buying apps.

You don’t whine about distractions, or derail yourself over needing a nicer pencil sharpener, or aggravate your chronic creative diabetes by starting another desperate waddle to the self-help buffet. No. You work.

And, for what it’s worth, just like you can’t get to the moon by eating cheese, you'll also never leave boot camp with your original scrote intact by telling your drill sergeant to try using more honey than vinegar.

No. That sergeant’s job is to make you miserable. It’s his job to break down your callow conceits about what’s supposed to be easy and fair. It’s his job to emotionally pummel you into giving up and becoming a Marine.

You? You're not there to give the sergeant notes; you're there to sleep two hours a night, then not mind getting beaten for 20 hours until a decent Marine starts to fall out.

Who knows? He may even surprise you by introducing a surprisingly effective “distraction-free learning environment.”

“Tee ell dee ahr, Professor Brainiac.”

Like most humans, I like things I can understand. Like most readers, I love specificity. Like most thinkers, I love clarity. Like most students, I love relevance and practicality. And, like most busy people, believe it or not, I actually do really like it when someone gets straight to the point.

But, here’s the problem. If my 2-year-old daughter asks me about time travel, and I blithely announce, “E=mc2”, I will have said something that is entirely specific, clear, relevant, practical, and/or straight-to-the-point. For somebody.

But, not so much for my daughter. And, to be honest, not even to any useful degree for me.

She'd probably either laugh derisively at me (which she’s great at), or she'd pause and ask, “Whuh dat?” (which she’s even better at).

Thing is, her understanding that jumble of characters less than me—and my understanding it WAY less than Professor Al—has zero impact on the profundity, truth, beauty, or impact of the man’s theory.

Sure. You could quite accurately fault me for being a smartass and a poseur, and you could even berate my toddler for her unaccountably shallow understanding of Modern Physics. But, in any case, you can’t really blame either Albert or his theory.

You're turbocharging nothing

Specifically, Albert can’t begin to tell us what he really knows if we don’t understand math.

So, let’s say this theory you've been hearing about really interests you. And, let’s also pretend, just for the sake of the analogy, that you haven’t completed Calculus III (212) or Quantum Mechanics (403) or even something as elementary as, say, Advanced Astrophysics II (537). I know you have. Obviously. But, let’s pretend. Where do you start?

Well, you could read some tips about learning math. You could find a list of 500 indispensable resources for indispensable math resources. You could buy a new “distraction-free math environment.” Heck, there’s actually nothing to stop you from just declaring yourself a “math expert.” Congratulations, Professor.

Thing is: you still don’t know math.

Which means you still can’t really understand the theory—no more than a pathetic Liberal Arts refugee like me or a dullard Physics ignoramus like my kid can really grok relativity.

Difference is, you will have blown a lot of time hoping that actual expertise follows non-existent effort—while my daughter and I get to remain total novices without charge. Only, we don’t get all mad at the theory as a result; a staggering number of fake math experts do.

I mean, be honest—after all that recreational non-work and make-believe dedication almost trying to kinda learn math sorta—you might actually get frustrated at how brazenly Al defies your fondness for shortcuts by continuing to rely on so many terms and proofs and blah-blah-blah that you still just don’t understand. So annoying.

You may simply decide that Albert Einstein’s a huge dick for never saying things that can be completely understood solely by scanning a headline.

EPIC EINSTEIN FAIL, amirite?

You never really know what you didn’t know until you know it

But, Al just told the truth.

Problem is, Al’s truth not only requires fancy things in order to be truly understood—the more of those fancy things you take away from his truth, the less true it gets. And, by the time it’s been diluted to the point where you're comfortable that you understand it? You'd be understanding the wrong thing. Even I can understand that.

But, not one bit of any of this is Al’s fault. Al doesn’t get to control who uses, abuses, gets, or doesn’t get what he said or why it matters. Especially since he’s been dead for over fifty years.

All I know is, regardless of who has ears to hear it on a given day, it would be to Al’s credit never to mangle something important in order to get it into terms everybody’s ready to handle without actually trying.

And God bless him for never agreeing that your “distractions” to learning math are his problem.

So, yeah, if you only need to hand in a crappy 5-page paper, you could certainly Cliff’s Notes your way through Borges, Eliot, or Joyce in an afternoon, and feel like you haven’t missed a thing. Trouble is, if you did care even a little, it’s impossible to even say how much you're missing since you can’t be bothered to soldier through the source text. The text itself is the entire point.

Even the wonderfully cogent and readable layman’s explanations Einstein himself provided don’t really get to the nut, the application, and the implications of his real theory.

That all takes real math.

That “single datum of experience” matters

Sometimes, complex or difficult things stop being true when you try to make them too simple. Sometimes, you have to actually get laid to understand why people think sex is such a thing. Sometimes, you need to learn some Greek if you really want to understand The Gospel of John. And, yeah, sometimes, you're going to have to just work unbelievably hard at whatever you claim to care about before anyone can begin to help you get any better—or less “distracted”—at it.

The part I really know is what doesn’t work. Reading Penthouse Forum won’t help you CLEP out of Vaginal Intercourse 101. Watching a Rankin-Bass cartoon about the Easter Bunny will teach you very little about the intricacies of transubstantiation. And, if you can’t be troubled to care so much about your work that you reflexively force distractions away, dicking around with yet another writing application will merely aggravate the problem. Ironic, huh?

These quantum mechanics of personal productivity are rife with such frustrating “paradoxes.”

These are True Things.

Achieving expertise and doing creative work is all horribly complicated and difficult and paradoxical and frustrating and recursive and James Joyce-y—and any guide, blog, binary, guru, or “nice guy” that tries to suggest otherwise is probably giving you a complimentary colonoscopy. Do the math.

Want a new syllabus? Sure:

Run straight into your shitstorm, my friends. Reject the impulse to think about work, rather than finishing it. And, open your heart to the remote possibility that any mythology of personal failure that involves messiahs periodically arriving to make everything “easy” for you might not really be helping your work or your mental health or your long-standing addiction to using tools solely to ship new excuses.

Learn your real math, and any slide rule will suffice. Try, make, and do until you quit noticing the tools, and if you still think you need new tools, go try, make, and do more.

If you can pull off this deceptively simple and millennia-old pattern, you'll eventually find that—god by dying god—any partial truth that’s supported your treasured excuses for not working will be replaced by a no-faith-required knowledge that you're really, actually, finally getting better at something you care about.

Which is just sublimely un-distracting.


Dedication

This article is dedicated to my friend, Greg Knauss. No, he’s not the app guy–he’s just a good man who does good work, who accidentally/unintentionally helped me write this rant. He also happens to be a fella who could teach anyone a thing or two about writing with distractions. Thanks, Greg.

“Distraction,” Simplicity, and Running Toward Shitstorms” was written by Merlin Mann for 43Folders.com and was originally posted on October 05, 2010. 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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Scared Shitless

Merlin Mann - "Scared Shitless: How I (Mostly) Learned to Love Being Afraid of Pretty Much Everything"

Download MP4 Video of "Scared Shitless"

This is the video of a talk I did last month at Webstock in Wellington, New Zealand.

It's pretty different from a lot of stuff I've done. It's about being scared.


As I mentioned on Back to Work, Webstock is—what? Well. Webstock is unique. Truly. If you get the chance, you should go. Really.

I could not and would not have done this talk in this way had I had not been so inspired (and, frankly, so terrified) by the awesomeness of the other speakers, by the quality of their talks, and by the astounding graciousness and empathy of the audience that this particular event attracts.

Tash and Mike and their crackerjack team have made something really special here. I'm honored that they even invited me, and I'm insanely grateful for the care and hospitality that they showed to the speakers and to the attendees at every step of the way.

Seriously. Thank you.


So, yeah. I did something really weird at Webstock. Weird for me and, honestly, just plain weird for "a talk."

I'm not sure if it succeeded. But, I did the best I could to make myself (along with some really heroic friends and fellow speakers) into a legitimate guinea pig for a concept that means the world to me:

You can be scared and still do it anyway. Regardless of whatever it is.

And, you can. No. Really. You. You can do this.

You can run toward the shitstorm, let it cover you with shit, but, still never let it stop you from running.

Because, like Crazy Bob says:

"They can't eat you."

And, they can't. And, they won't. Okay?

Well, okay, then.

Scared Shitless” was written by Merlin Mann for 43Folders.com and was originally posted on March 28, 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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Consume First, Deal with the Shit Later

Websites are Blocking the Wrong AI Scrapers (Because AI Companies Keep Making New Ones) – 404 Media *** I had a call the other day with the Dean of a top-five school of public health, and in between furiously scribbling notes (yes, I still take notes), it struck me that here in the United States … Continue reading "Consume First, Deal with the Shit Later"





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The REAL Harm Done By Calling Everyone You Don’t Like ‘Hitler’ Is BIGGER Than Lefties Think

There's a reason Hitler holds a special place of disgrace in public memory. He combined the ambition and destruction of Attila The Hun with the personal malice of a serial killer.

The post The REAL Harm Done By Calling Everyone You Don’t Like ‘Hitler’ Is BIGGER Than Lefties Think appeared first on Clash Daily.




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Mark Milley Fears He Will Face a Court-Martial When Trump Enters White House

Retired Gen. Mark Milley is afraid of retribution. The former chairman of the Joint Chiefs of Staff and a four-star Army general made no bones about his feelings about former […]

The post Mark Milley Fears He Will Face a Court-Martial When Trump Enters White House appeared first on The Western Journal.




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Inside the White House




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Humanitarian Responders in Syria: The White Helmets





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Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding [Glycobiology and Extracellular Matrices]

VAR2CSA is the placental-malaria–specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative-stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of infected red blood cells and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria.




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Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging [Protein Structure and Folding]

Connexin (Cx) protein forms hemichannels and gap junctional channels, which play diverse and profound roles in human physiology and diseases. Gap junctions are arrays of intercellular channels formed by the docking of two hemichannels from adjacent cells. Each hexameric hemichannel contains the same or different Cx isoform. Although homomeric Cxs forms have been largely described functionally and structurally, the stoichiometry and arrangement of heteromeric Cx channels remain unknown. The latter, however, are widely expressed in human tissues and variation might have important implications on channel function. Investigating properties of heteromeric Cx channels is challenging considering the high number of potential subunit arrangements and stoichiometries, even when only combining two Cx isoforms. To tackle this problem, we engineered an HA tag onto Cx26 or Cx30 subunits and imaged hemichannels that were liganded by Fab-epitope antibody fragments via atomic force microscopy. For Cx26-HA/Cx30 or Cx30-HA/Cx26 heteromeric channels, the Fab-HA binding distribution was binomial with a maximum of three Fab-HA bound. Furthermore, imaged Cx26/Cx30-HA triple liganded by Fab-HA showed multiple arrangements that can be derived from the law of total probabilities. Atomic force microscopy imaging of ringlike structures of Cx26/Cx30-HA hemichannels confirmed these findings and also detected a polydisperse distribution of stoichiometries. Our results indicate a dominant subunit stoichiometry of 3Cx26:3Cx30 with the most abundant subunit arrangement of Cx26-Cx26-Cx30-Cx26-Cx30-Cx30. To our knowledge, this is the first time that the molecular architecture of heteromeric Cx channels has been revealed, thus providing the basis to explore the functional effect of these channels in biology.




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Fighting over ‘white gold’: Sesame in Ethiopia and Sudan

Fighting over ‘white gold’: Sesame in Ethiopia and Sudan Expert comment LJefferson 3 April 2023

The supply chain of a seemingly innocuous cash crop – sesame – has intersected with transnational conflict dynamics, exacerbating tensions between Ethiopia and Sudan.

Late 2020 saw the beginning of the devastating war in Tigray and the occupation of a disputed region on the Ethiopia–Sudan border – Al Fashaga – by the Sudanese army. These shocks disrupted settled patterns of land ownership and control in both Ethiopia’s volatile north and Sudan’s borderlands, historically the heart of the sesame and oilseed production that is economically vital to both countries.

These seemingly harmless cash crops are now embedded in local, subnational and national political contestations in both countries. Sesame value chains are being reshaped, with power and profits being used to entrench the grip of political and armed actors who are reinforcing new patterns of land control and driving informal and illicit trade – impacting the coping mechanisms of local communities and threatening to fuel further conflict.

Regional rivalries drive contestation over the Ethiopia supply chain

Internal borders between most of Ethiopia’s regions are marked by boundary disputes, which often degenerate into violent conflict. The most important is between the Tigray and Amhara regions. Since the war began in 2020, the Amhara region has annexed vast areas of western and southern Tigray, which the Amhara region claims were taken from them by Tigray 30 years ago, after the Tigray People’s Liberation Front (TPLF) dominated ethnic coalition came to power.

Conflict has exacerbated a steady decline in formal revenues from sesame exports, dropping over $115 million from 2016 to 2021.

Ethiopia’s exports of spices, oilseeds and pulses brought in over half a billion dollars in 2021, roughly a quarter of the country’s total export revenues and second only to coffee. The sector has been rocked by the war in the north, which accounted for much of Ethiopia’s sesame production, with an estimated 500,000 hectares of sesame fields taken out of cultivation during the 2021 growing season. Conflict has exacerbated a steady decline in formal revenues from sesame exports, dropping over $115 million from 2016 to 2021.

Alongside falling production, the previously integrated value chain has been disrupted and decentralized by political fragmentation and land competition between Amharas and Tigrayans. Before the war, the agricultural sector in Western Tigray/Welkait was dominated by Tigrayan business interests, through the TPLF’s regional endowment fund EFFORT, a business conglomerate including subsidiaries such as Guna Trading House, and Hiwot Agricultural Mechanization.

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Two-minute video explainer: Supply chains, land contestation and conflict in the Horn of Africa

The taking of the area by Amhara forces in late 2020 saw the control over agricultural supply chains shift to actors from the Amhara region, amid contestation between regional officials, businessmen and security actors, backed by political elites. Thousands of displaced ethnic Tigrayan inhabitants of the area have been replaced by ethnic Amharas, enticed to settle there by the Amhara regional government’s offer of grants and leases for land which promise better livelihoods. The sesame they farm is now largely exported through informal and illicit channels, with profits used to reinforce de facto regional control.    

But there is also contestation within the Amhara region over the land and sesame supply chain between sub-regional elites from Gojjam, Gondar and indigenous Welkaites. Welkaites, who were marginalized under TPLF rule, believed that by aligning themselves with powerful Amharas they would reclaim land and influence. But this has not been fully realized, with the local administration reliant on Amhara region subsidies, rather than the federal budget. With little support from the federal government, local Welkait officials are strengthening their ties with Eritrea.

The Ethiopian government’s pursuit of peace with Tigray may lead it to turn away from the Amhara region, which could result in a renewed showdown between Amhara and Tigrayan forces.

At the national level, regional contestation over the control over Western Tigray/Welkait feeds into shifting political alliances between the Amhara, Tigrayans and Oromo which threaten the sustainability of the peace agreement struck between the federal government and TPLF in November 2022 – despite efforts by the government to defer the thorny issue.

While the constitutional return of the land to Tigray remains unlikely anytime soon, there is a feeling that Amhara control over Western Tigray/Welkait is no longer certain. The Ethiopian government’s pursuit of peace with Tigray may lead it to turn away from the Amhara region, despite their alliance during and before the war, which could result in a renewed showdown between Amhara and Tigrayan forces.

The prospect of losing territory could also heighten Amhara nationalist claims on Al Fashaga – the loss of which was partly offset by gaining Western Tigray/Welkait – leading to renewed conflagration with Sudan, outside of federal direction. Eritrea’s presence and alliance with Amhara militias remains a concern, given Asmara’s demonstrable ability to inflame tensions.  

Sudan’s securocrats battle over resources to entrench political power

The war in northern Ethiopia was also used opportunistically by the Sudanese Armed Forces (SAF) to take control of the fertile Al Fashaga borderland. This roughly 250 sq km area had been awarded to Sudan when the boundary was initially demarcated by the British in 1903, a ruling that remained contested by Ethiopia. An uneasy truce had seen Ethiopian farmers cultivate the land under nominal Sudanese administration; a settlement that collapsed in 2020 when thousands of predominantly Amhara farmers were evicted.

Local Sudanese farmers have also lost out – with some not compensated for the loss of lands to their own military, with land given to people from other parts of the country, and through lost relationships with Ethiopian farmers, labourers and investors.

The Sudanese military now allegedly controls more than 90 per cent of the disputed areas and security-linked companies and investors have moved into the lucrative sesame sector, re-routing the supply chain, which used to flow largely through Ethiopian markets. These companies are connected to Sudan’s Military Industrial Corporation, a vast conglomerate of business subsidiaries controlled by SAF – which is headed by General Abdel Fattah al-Burhan.

Competition between Sudanese security actors fuels volatile political rivalries, and further entrenches military control of economic resources.

The commander of the paramilitary Rapid Support Forces, General Mohamed Hamdan Dagolo (or Hemedti), also has interests in agriculture, through his family business Al-Junaid. Both sit at the top of Sudan’s Sovereign Council. Hemedti’s competition with Burhan has seen him develop relations with Ethiopia’s prime minister – counter-balanced by recent rapprochement between Abiy and Burhan – as well as senior Amhara leaders, including over business activities.

Moreover, competition between Sudanese security actors fuels volatile political rivalries, and further entrenches military control of economic resources, undermining civilians at a time when pro-democracy forces are seeking to restore a reform-minded government. One of the key challenges for a new civilian government will be to quickly build up a domestic revenue base to compete with the economic heft of the country’s prominent security institutions, which will demand taking on military-controlled holdings in civic sectors such as agriculture, including sesame.

Informal and illicit trade reinforces conflict dynamics

This context has driven the informalization of trade, with cash crops such as sesame increasingly exported outside of formal channels and connected to other illicit cross-border activities between Ethiopia and Sudan. Indications are that sesame production in Western Tigray/Welkait has recovered significantly during the current 2022/23 harvest season. However, rather than contributing much needed currency to soften Ethiopia’s forex crisis, the Amhara elite-controlled supply chain is primarily being used to secure a variety of regional interests.




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