Iran will pursue whatever secures its interest, government spokesperson Fatemeh Mohajerani said on Tuesday, when asked if there could be direct talks with the Trump administration.

The United Nations's humanitarian aid chief told a meeting of the Security Council (UNSC) that "acts reminiscent of the gravest international crimes" are being committed in Gaza.

The itinerary on my 13-day Norwegian cruise was too packed. Spending only two of the 13 days at sea left me exhausted, even as a seasoned cruiser.

The rental-car giant fell as much as 12% on Tuesday after posting a deeper-than-expected loss.

Ducati North America CEO Jason Chinnock enlisted in the US Army out of high school and served with the Third Armored Division in Desert Storm.

It's a British heritage brand driven by royals, including the late Queen Elizabeth. Now new Jaguars won't be on UK car lots until at least 2026.

Taylor Swift is known for her glamorous red-carpet looks and sparkling stage outfits. But she's also fashionable in her everyday life.

Apple's smart home device, featuring AI and FaceTime, could enter the market by March, Bloomberg reported, and could compete with Google and Amazon.

Financial planner Anthony Carlton says his richest clients are teachers and other unassuming professionals who have good money habits.

The ARJ21 is now to be known as the C909. The renaming plays into COMAC's ambition to enter the global market.

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 […]

Mauritians are set to find out who will govern their Indian Ocean island nation for the next five years after a hotly disputed election race.

Tuesday 12 November 2024 – Flockerz ($FLOCK) has reached $1.5 million in its presale, as the meme coin market sees… Continue reading Flockerz Presale Reaches $1.5M as Meme Coin Market Hits $111B

The post Flockerz Presale Reaches $1.5M as Meme Coin Market Hits $111B appeared first on ReadWrite.

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.

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.

International Relations and Cooperation Minister Ronald Lamola threw diplomacy out the window on Tuesday and responded angrily when he was asked whether South Africa and the ANC were "protecting its friend" Frelimo in troubled Mozambique.

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.

An underwater rover deployed by the Minderoo-UWA Deep-Sea Research Centre captured remarkable footage 3,300-meters down at the bottom of the Tonga Trench. It shows a rarely-seen bigfin squid (Magnapinna) "taking a walk" on its 13-foot tentacles. Watch below.

There have only been around 20 documented sightings of this beautifully bizarre creature in two decades. — Read the rest

The post Deep sea video of weird sea creature walking around on its 13-foot "legs" appeared first on Boing Boing.

Video is beginning to fulfill its promise as a transformational technology. Beyond merely cutting communications costs, video is starting to change the way companies do business, and is rapidly being accepted as a "need to have" rather than a "nice to have."

Cisco CEO John Chambers predicts video traffic on the internet will increase six fold by 2012. Here is a link to Cisco's August 5 earnings call where he makes that prediction.

A classic example of the power of video is that of electronics manufacturer NEC. They have a network of nearly 500 dealers across the United States that sell their products. They saved more than $250,000 annually in training costs by delivering product training with video webcasting rather than sending trainers to the dealers or bringing the dealers to the trainers.

They also dramatically reduced the time it takes to train the entire network on new products. Click here to watch a video case study.

A newer example shows how video can literally transform the way a company does business. A major sneaker company manufacturers its products in China. Each time they re-tooled to manufacture a new sneaker, executives would have to fly to China to ensure the tooling was correct and the sneakers were meeting specifications before they began mass production.

They began to use high definition cameras at the plant in China to webcast video of the sneakers to allow executives to make their inspection virtually. Sure, they save money on travel to China. But more importantly, there was a practical limit to the amount of people who could go to China to see the actual design come off the assembly line. The video process allows them to solicit input from a much broader segment of the company, and even get input from retailers while there is still time to respond to suggestions.

The end result is that they can bring their products to market faster than their competition, which creates a significant competitive advantage. Click here to see the video discussion.

I am particularly pleased to see clear evidence of unmistakable, game-changing ROI.

The following article, Lunatic Democrat Murders Wife and Kids, Commits Suicide Over His Hate for Donald Trump, was first published on Conservative Firing Line.

This is how mentally deranged liberals are… a Democrat in Minnesota was so filled with rage that Donald Trump won the election last week that he murdered his own wife and kids and then committed suicide to prevent them all from having to live during the next Trump presidency. Notice how you never heard any …

Continue reading Lunatic Democrat Murders Wife and Kids, Commits Suicide Over His Hate for Donald Trump ...

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.

Five years ago I was posting a lot to a publication called NewCo Shift, which is now offline. I got ahold of the archives, and found this review, which hasn’t lost any of its relevance – in fact, it kind of reads like it was written last week.  Everyone in tech loves Yuval Noah Harari. … Continue reading "From the Archive: Tech Must Get Over Its Superman Complex, Or We’re All Screwed"

Wednesday's third T20 between South Africa and India at SuperSport Park in Centurion is shaping up to be a run-drenched one, especially if the weather holds and SA's bowling centre doesn't.

Springbok team doctor Jerome Mampane says that injured utility back Sacha Feinberg-Mngomezulu is recovering well.

Junyi Xie
J. Amer. Math. Soc. 38 (), 1-62.
Abstract, references and article information

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.

Roland Bruderer
May 1, 2015; 14:1400-1410
Research

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.

G20 must live up to its crisis-solving legacy Expert comment NCapeling 29 October 2021

The relevance of G20 is in question amid waning internal cohesion, but emerging economies could inject the group with inclusive ideas and greater legitimacy.

‘If we didn’t have it, we would have to invent it’ might well be the catchphrase for the Group of 20 (G20) as the international community rethinks global institutional architecture in the face of shifting power dynamics and geopolitical strife.

To be fair, the same is often said of other venerable institutions such as the World Trade Organization (WTO), or even the United Nations (UN), often as a line of defence when questions are raised over their relevance or effectiveness.

According to former Goldman Sachs Asset Management chairman and UK treasury minister Jim O’Neill, size also matters because the G20 is both too big and too small to be on the ball consistently. While he might be right, numbers alone suggest the G20 should be the room where it happens when it comes to fixing global challenges such as post-pandemic economic recovery, tackling climate change, or getting the world vaccines.

Of all the international groupings, it boasts the most diverse and compelling mix of nations. It has 80 per cent of global income, three-quarters of global exports, 60 per cent of the global population and 80 per cent of global emissions.

Coming of age

The G20 was a forum of central bankers and finance ministers created when the 1997 Asian financial crisis laid bare the insufficiency of the G7. It came of age in 2008 when elevated to a leaders’ level summit two months after the Lehman Brothers collapse that precipitated the global financial crisis.

Perhaps distance did make the heart grow fonder, or at least hindsight rosier. While the G20’s response to the 2008 global financial meltdown is often lauded as an exemplary economic crisis response, the reality is less straightforward.

Barely two days after solemn promises were made in the 2008 communique, Russia broke rank and raised tariffs on imported cars. India followed by applying import duties on several iron and steel products.

Even though the 2008 summit did not immediately result in a coordinated fiscal boost, the common threat of a global financial meltdown helped conjure a display of global unity and rally much-needed market confidence. It also resulted in a set of practical action plans unheard of to that point and specific tasks for several international organisations as a follow-up to summitry.

The seeming parallel to 2008 this year, as the world faces the common threat of the COVID-19 pandemic amid a series of extreme weather and supply crunches, explains why expectations are running high for Rome and for G20 president Mario Draghi, the Italian prime minister.

There is pressure to solve myriad global challenges, whether scaling climate action before the UN climate change conference in Glasgow or delivering vaccines and debt relief for developing countries, to name a few.

Effective crisis response is how the G20 has cut its teeth, and the world is handling several emergencies right now. Draghi himself was chair of the Financial Stability Forum back in 2008.

Inflated expectations also abound because the Rome gathering is a G20 summit without the long shadow of Jamal Khashoggi’s death over the Saudi G20 presidency. It also lacks former US president Donald Trump, who tried his best to put many international organisations and the spirit of global cooperation in deep freeze since 2016.

If defrosting multilateralism was also a shared goal, in addition to economic recovery, general rustiness in the business of international cooperation – an understandable hangover from the Trump years – has also gummed up the works.

Hence, the G20 will have to do much in the coming days to prove that, unlike the G7 in 2008, it has yet to outlive its usefulness, even when some have decried it as being missing in action over the COVID-19 crisis. Amid rising US-China tensions and at a critical juncture for the global economy, countries are wondering if the G20 will survive such a tense geopolitical atmosphere and whether the agenda will be overloaded with challenging foreign policy issues such as the plight of Afghanistan.

Customary language aside, the G20’s problem-solving reputation can be oversold. Not surprisingly, it has worked best when members already agree on the next steps. Looking to the future, more hostile power plays are likely to further weaken the cohesiveness and effectiveness of institutions such as the G20.

Reviewing its track record would also suggest the institution’s prowess in crisis response tends to wane with the distance from the realm of monetary policy coordination. Not all areas of macroeconomics are created equal, in part because of the professional camaraderie and insularity of the central banking technocracy.

As was evident even in 2008, the G20 was less effective where there were more actors and domestic political dynamics at play, such as in the arena of trade. The recent deal struck on corporate tax is an encouraging but notable exception.

Gap between words and deeds

As The Economist said in 2011: ‘the G20 … is a big improvement over the G7 because it takes emerging economies seriously. But do the emerging economies themselves take the G20 seriously?’ Any scorecards would point to severe gaps between words and deeds, most notably but not limited to the emerging economy members.

If the G20 was born out of the need to increase the number of seats at the table, the next three years – with the G20 helmed by Indonesia in 2022 followed by India then Brazil – might prove to be the coming-out party for emerging economies.

Redefine the Commonwealth now to safeguard its future Expert comment NCapeling 6 October 2022

Although seen as one of the Queen’s greatest legacies, the Commonwealth must provide tangible benefits to its citizens in an era of geopolitical competition.

The Commonwealth’s breadth allows a wide diversity of countries of different sizes, geographies, cultures, and values to be members – it is both rich and poor, north and south, and ethnically diverse. This makes it more interesting than many other multilateral institutions such as the G7, NATO, and the European Union (EU).

But it suffers from an unclear purpose. Since its inception, successive UK governments have grappled with its role – whether it is a preferential trading bloc or merely a source of most of Britain’s post-war immigration.

This lack of purpose – and structure – has left the Commonwealth impotent in dealing with a host of bilateral difficulties between the UK, its overseas territories, and Commonwealth partners in recent years.

Brexit could induce Britain to re-prioritize the Commonwealth, but so far the UK has only signed two new trade deals with Commonwealth members – Australia and New Zealand – while development aid, one of the most tangible ways the UK worked with many Commonwealth countries, has been cut and the UK’s defence focus has pivoted towards the Indo-Pacific and Europe’s Eastern front.

The UK also suffered embarrassing and overwhelming defeats in both the UN General Assembly (UNGA) and the International Court of Justice (ICJ) on the legality of its continued occupation of the Chagos Islands and has avoided directly challenging India’s tacit support for Russia’s invasion of Ukraine in the hope of securing a trade deal.

At the recent Commonwealth Heads of Government Meeting (CHOGM), Boris Johnson reportedly attempted to depose Baroness Scotland, the Commonwealth’s Secretary General, but suffered a humiliating defeat in a vote of Commonwealth members.

These challenges are likely to continue, especially in the wake of the death of HM The Queen which could be seen by republican movements as an opportune time to rally support. Australia and New Zealand’s leaders, both republicans, downplayed the idea of a poll on the monarchy immediately after the Queen’s death, but it would be a mistake to assume this has gone quiet forever. Antigua and Barbuda’s prime minister has already said there will be a referendum on becoming a republic within three years.

Defining a new vision for the future

A concrete vision for the Commonwealth is long overdue and there is no better time to cast one than now. HM The Queen was more than just a figurehead for the Commonwealth and it remains unknown exactly what role King Charles III will see for himself.

But, unlike his mother who was a young, modern Queen heralding a post-imperial future, Charles takes the throne at a later age and at a time when important questions need to be addressed in an increasingly fractured world.

Most importantly the UK should avoid the temptation to define the Commonwealth in terms of shared principles and values. India, Pakistan, and Bangladesh all abstained on the United Nations (UN) motion condemning Russia’s invasion of Ukraine, and Commonwealth members are likely to be similarly divided over China’s territorial claims, the US-China conflict, the net-zero agenda, and nuclear non-proliferation.

The Commonwealth’s breadth – its greatest strength – means consensus is often impossible, and so should not be the goal. Instead the Commonwealth should focus on tangible areas of cooperation where there is mutual interest such as trade, aid, and migration.

The UK and its allies may find that diplomatic efforts – such as condemning China or Russia for human rights abuses – are more successful if they have listened to and acted on fellow Commonwealth countries’ concerns, from post-COVID vaccine provision to climate financing. Boosting the aid budget and opening borders may prove more important in engaging developing country partners than traditional diplomatic avenues.

Liz Truss’s British International Investment project could be a valuable vehicle for financing, especially if it leverages private sector funding, but many Commonwealth countries are feeling the more immediate impact of the UK’s aid cuts. In these circumstances many have already turned to Chinese infrastructure financing.

This is where the Commonwealth could be valuable. In the Pacific, it links certain island nations to the UK, Australia, and New Zealand at a time of renewed geopolitical competition with China in the Pacific. The fact the Commonwealth is not explicitly about promoting a particular ideology or countering China is helpful.

Commonwealth should be less UK-centric

There is also no reason why all the Commonwealth operations need to be based in London, which is not only expensive but also reinforces an approach to governance that assumes everything must be decided by civil servants in London. As the world’s largest democracy, India is an obvious alternative candidate although its reluctance to condemn Russia’s invasion and its domestic political tensions may count against it.

It is also important the Commonwealth’s wealthier members – the UK, Canada, and Australia – provide financing for countries such as India to take on extra responsibilities. The Commonwealth Games is a good place to start – despite having 72 competing nations and territories, the games have only been held three times outside the UK, Canada, Australia, and New Zealand.

The Commonwealth also needs to be forward-looking and one of its most exciting assets is its demographic youthfulness. Europe, China, and the US have ageing populations whereas Nigeria, India, and Bangladesh have some of the world’s largest young populations.

After Truss, the UK can still rebuild its global reputation Expert comment NCapeling 20 October 2022

Following a chaotic few weeks as UK prime minister, Liz Truss has stepped down. And that is the best outcome for her party and for the country.

Liz Truss could not command support for her calamitous – and misnamed – mini-budget. And once her new Chancellor Jeremy Hunt had overturned its provisions, she had no mission or credibility left.

The budget pushed interest rates higher and they did not fall much on the scrapping of it, leaving her open to the charge she pushed up mortgage and interest costs for every person and business in the country. Her apology for ‘mistakes made’ was not going to reverse that, so her MPs were right to tell her to go.

Her departure does mark a victory for at least some of the UK’s institutions, even if it might not seem that way to observers around the world.

The position of the UK parliament has been reaffirmed, and so has that of the Office for Budget Responsibility (OBR) – it will be a long time before a government tries to dispense with the comments of the independent watchdog of national finances.

This also reinforces the principle that governments must explain how they will pay for their programmes. The Bank of England remains unencumbered – despite Truss’s apparent intentions of giving it a pro-growth addition to its mandate – to pursue its aim of tackling inflation.

New leader needs legitimacy quickly

The Conservative party has a chance – perhaps – to produce another prime minister without being forced into a general election, as that is the constitutional principle in the UK’s parliamentary system.

But the clamour that the new leader, as the third prime minister in one year, lacks legitimacy may prove impossible to resist for long.

In attempting to select a leader with a chance of uniting the party, the Conservatives are right to be considering options for restricting this leadership election to MPs should there be only one candidate with enough support.

But no such candidate may emerge and the pressure within the Commons – and the country – for an early election will not let up.

There is no question the UK’s standing in the world has been severely battered by this episode and by the revolving door of prime ministers. For the UK to regain respect – and an image of reliability – it needs to move fast and find someone capable of putting policies into action.

Those policies need to be based on economic stability but must also include a resolution of the relationship with Europe as much of the current upheaval represents the bitter aftermath of Brexit.

Concluding a deal with Brussels over the Northern Ireland protocol – avoiding ripping up the treaty the UK signed – and continuing to smooth the considerable friction that the exit from the EU has brought for exporters is essential work for the next prime minister.

Pursuing a deal for scientists to take part in the European Union (EU) Horizon research should be a priority. UK universities and researchers are already reluctantly preparing for a future where that does not come, with signs of the feared drain of talent already clear.

UK’s international reputation now at risk

Beyond that, there is much about UK policy which needs clarifying if the country is to regain its international standing. Just weeks from the start of COP27 and less than one year since the Glasgow climate change summit it hosted, the UK position on climate change commitments appears in flux.

The UK government pledge to help Ukraine is clear and has won it gratitude there and respect within Europe, but its intentions for defence spending are less clear.

The UK must focus on how the Chagos decision is implemented to gain its benefits and minimize risks Expert comment jon.wallace 11 October 2024

The UK decision was welcomed by India and the US, and shows a capacity for fresh thinking. But the transfer of sovereignty must be handled carefully.

The UK announced on 3 October that it would cede sovereignty over the Chagos Archipelago to Mauritius.

There are potential strategic and reputation-related upsides for the UK from the decision – but these can only be realized if the deal is implemented in ways that meet the UK’s stated goals.

First, the UK aims to safeguard the utility and security of the joint US–UK base on Diego Garcia. It also intends for the decision to benefit the Chagossians, who were displaced by the British decision in 1965 to separate the Archipelago from Mauritius as part of a deal to grant Mauritian independence.

The decision has already proved deeply controversial in the UK, provoking sustained criticism from former Conservative government ministers and commentary that has branded it naive, dangerous, and a blow to British prestige.

Part of the reason for the welter of criticism may be the apparent suddenness of the announcement. The impression that this was a hasty decision is likely because it came just three months after the Labour government came to office. But this belies the far longer gestation period around the decision.

World opinion

In fact, the previous Conservative UK government decided to begin negotiations over sovereignty of Chagos – following Mauritius bringing the matter to the International Court of Justice. In 2019, the court issued a non-binding opinion in favour of Mauritius.

The same year the UN General Assembly voted 116 in favour to 6 against, and with 56 abstentions, for a resolution ‘welcoming a 25 February 2019 International Court of Justice advisory opinion on the legal consequences of separating the Chagos Archipelago from Mauritius in 1965, demanding that the UK unconditionally withdraw its colonial administration from the area within six months’ to ‘enable Mauritius to complete the decolonization of its territory.’

But returning the islands will not necessarily boost the UK’s international standing. Issues relating to the Archipelago are complex, and it will take work to convince interested international parties that the UK is acting fairly against a colonized and displaced population.

Mauritius has no pre-colonial history of controlling the Chagos islands, which are located some 1,500 miles away from Mauritius across a vast sprawl of the Indian Ocean. It is true that the Chagos Islands were a colonial remnant, but to ensure that UK is seen by global audiences to be acting fairly, the handover of sovereignty must be carefully handled. Perhaps the greatest reputational risk will come from failing to adequately account for the rights of Chagossians.  

The more pertinent historical injustice has been to them. And reporting by the BBC has shown that at least some Chagossians were dismayed by not having been consulted in negotiations between the UK and Mauritius.

The UK government announcement on the deal did state that that ‘the welfare of Chagossians’ will be paramount and that ‘the UK will capitalize a new trust fund, as well as separately provide other support, for the benefit of Chagossians’. But for the Chagossians, there will be a clamour to see this realized in full.

Strategic interests

On the strategic question, the utility of the joint US–UK military base on Diego Garcia has been guaranteed in a 99-year lease. As the UK negotiator Jonathan Powell has explained, this deal was reached in close consultation with US officials and puts the base on legally safe ground for the first time in decades. 

Indeed, Powell has explained that Joe Biden was keen to reach agreement ahead of the US elections so that US military access to Diego Garcia was safeguarded against any possible contrary decision by a possible returning Trump presidency.

There are understandable concerns that, as a result of the decision, China may develop commercial ports in the region and seek to compete with India for economic and strategic relationships. But this is a long-term matter of concern to monitor, regardless of the UK’s decision on Chagos.

Chinese naval influence in the Indian Ocean is currently limited, compared to its assertiveness in the South China Sea, where it is building artificial islands, or in the South Pacific where it is pursuing policing assistance deals like that secured with the Solomon Islands.

And the strategic situations in the Pacific and Indian Oceans are not at all alike. Indeed, the Chagos Islands are far closer to India and its economic influence than they are to any other major economic power. 

The fact that India has welcomed the UK’s decision over Chagos sovereignty is noteworthy, given the UK’s separate attempts to modernize and expand its bilateral relations with New Delhi.

In the long run, it is likely that India will play a leading role in Indian Ocean security, and the UK will want to be well-placed to explore how to play a role as an effectively partner.

The more pertinent immediate concern is the implications for other overseas UK territorial responsibilities. There are legitimate questions to be raised over setting a precedent that could undermine RAF Akrotiri and Dhekelia in Cyprus, which remained sovereign UK bases after Cyprus’s independence in 1960.

Independent Thinking: How can France survive its budget crisis? Audio john.pollock 17 October 2024

Sophie Pedder and Shahin Vallée join the podcast to discuss France’s contentious budget and political drama, and the potential impact on Europe and beyond.

On this episode

France is facing political turmoil. The survival of Michel Barnier’s new government rests on whether he can pass a controversial budget intended to rescue the country from its huge fiscal deficit. Bronwen Maddox is joined by Sophie Pedder, the Paris bureau chief of The Economist, Shahin Vallée, a former adviser to Emmanuel Macron and Armida van Rij, the head of our Europe Programme.

About Independent Thinking

Independent Thinking is a weekly international affairs podcast hosted by our director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

More ways to listen: Apple Podcasts, Spotify.

How to revive Europe’s economy and unlock its potential 7 November 2024 — 6:00PM TO 7:00PM Anonymous (not verified) 22 October 2024 Chatham House and Online

Enrico Letta, former prime minister of Italy, and other experts discuss how the European Union’s economy must adapt to a challenging world.

Amid a fractured geopolitical environment, global trade volatility and hardening protectionist policies in many countries, the European economy must adapt fast. The single market is a key driver of European integration, but it was designed in a very different global economic context.

Launched in April, Enrico Letta’s Much more than a market report set out how the European Union should adapt the arrangements of the single market to ensure it delivers prosperity and economic security for EU citizens in the 21st century. The report resonates with ongoing debates over the future of European competitiveness, industrial strategy and how to respond to an apparently deglobalizing world. In this event, Letta and other experts on the European economy and integration will discuss the prospect of meaningful reform of the single market, and what the incoming Commission can do to ensure the EU unlocks the potential of its economy for all its citizens.

Key questions will include:

• What dynamics are shaping the Europe’s economic landscape?
• What opportunities are there to enhance the strength and competitiveness of the single market
• How can the EU’s leaders ensure the single market is aligned with other strategic objectives such as security and enlargement?
• What political hurdles may prevent progress on single market reform? And how can these be overcome?

The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct.

Following its snap election, Japanese politics has entered uncharted waters Expert comment LToremark 5 November 2024

Prime Minister Ishiba’s election gamble has failed. Japan now faces another period of political uncertainty, which could affect its international standing.

In Japan’s snap election on 27 October, the ruling coalition of the Liberal Democratic Party (LDP) and New Komeito lost the overwhelming majority it had held since the 2012 general election. The ruling coalition now has 215 seats, leaving it 18 seats short of a majority. 

The largest opposition party is the Constitutional Democratic Party of Japan (CDP), which gained 50 seats to 148. The second largest opposition party is the Japan Innovation Party (Ishin), which lost six seats to 38, and the third largest opposition party is the National Democratic Party (NDP), which gained 21 seats to 28.

But the opposition is divided and there is no real appetite to form a coalition government. This will likely result in a hung parliament, which will further destabilize Japan’s government.

The election results reveal three key things  about the state of Japanese politics and what comes next.

First, that Prime Minister Ishiba’s snap election gamble has failed. The aim was for Ishiba, a non-mainstream member of the LDP, to strengthen the party base and stabilize his administration. But with the ruling coalition losing its majority, the party base has been further weakened and the Ishiba administration is now more likely to be short-lived. LDP voters as well as the public in general  had hoped that Ishiba, as the ‘opposition within the party’, would change the LDP’s structure and government policies, eliminate the uncertainty surrounding party funding and increase transparency on how MPs use public funds to finance political activities.

However, when Ishiba became LDP leader and prime minister, he abandoned his previously more critical stance and prioritized carrying on the policies of the mainstream LDP, leaving his supporters feeling betrayed.

Second, while the ruling coalition has been punished, the people of Japan still did not vote for a change of government. The opposition is divided and, despite its gains in this election, the CDP is not fully committed to take the lead and consolidate the opposition to form a coalition. The CDP also suffers from internal division. The left wing of the party would prefer a coalition with the Communist Party, while the right wing of the party does not want to form a coalition with the LDP or the Communist Party, preferring a partner such as the NDP.

Third, the NDP has become the key to future Japanese politics. By becoming the minority ruling party, the NDP is in a position to control the fate of Ishiba administration. While the CDP has no intention of cooperating with the LDP, the NDP is more willing to do so in order to implement its own policies. As the budget cannot be passed without the NDP’s cooperation, the ruling coalition will have no choice but to accept the NDP’s policy of substantial tax cuts through the expansion of tax credits. It will also likely have to accept an option for married couples to decide their family names, which requires a change of civil codes and is something it has been reluctant to do so far. 

If the NDP’s demands are rejected, a no-confidence motion will likely be submitted and passed, leaving the Ishiba cabinet with no choice but to resign or dissolve the House of Representatives (the lower house of Japan’s parliament).

But the NDP has chosen to not form a coalition with the ruling party and enter government. Why? From the NDP’s point of view, forming a coalition with the LDP, would mean getting involved in the LDP’s internal turmoil – something it wishes to avoid. In addition, elections to the House of Councillors (upper house of parliament) will be held in the summer of 2025. The NDP may have judged that it will have a better chance of implementing its policies by cooperating with the government on a case-by-case basis, rather than forming a coalition with a party that is losing public support and risk following suit.

The minority ruling system that has emerged after the election is extremely rare in Japan’s political history and is likely to make its politics even more unstable in the years ahead. The Ishiba administration will probably be able to survive until the budget is passed in March next year by cooperating with the NDP, but beyond that its prospects are unclear.

As the House of Councillors elections get closer, some in the LDP may say that they cannot fight the election with Ishiba as prime minister. If so, they may choose the option of a same-day election for the lower and the upper house. The cost of an election campaign is significant, and the LDP’s financial strength gives it an advantage in the case of a same-day election. There is also a strong possibility that the public will choose the LDP to regain stability in government. However, this election has shown that public distrust of the LDP is high, and if Ishiba continues to be pushed around by the NDP, his party’s chances of winning would be reduced.

Japanese politics has entered uncharted waters, where the patterns and customs of the past do not apply. There are now doubts both at home and abroad as to whether Ishiba, who has a weak party base, will be able to stay on and steer the government. Over the past decade, the Abe and Kishida administrations have provided Japan with political stability, which has in turn enhanced its international presence. An unstable political system, with frequent changes of government, will likely lead to a decline in Japan’s international influence.

There is also a risk that US–Japan relations  could become unstable. Although the NDP does not have a strong agenda to change the course of this relationship, Ishiba may struggle to keep the promise made by his predecessors to increase defence spending. Ishiba’s nationalist posture could also create a confrontational relationship with the United States, while his weak leadership means he may not seek to invest in strengthening the US–Japan alliance. 

Donald Trump’s win in the US presidential election could pose a further risk. Although Trump might be open to Ishiba’s demand for parity with the US, he could become irritated with Ishiba’s weak domestic position. Ishiba may not be able to make decisions – or a deal with Trump – unless the NDP agrees to it.

Mohamad Navab
Sep 1, 2000; 41:1495-1508
Articles

Mohamad Navab
Sep 1, 2000; 41:1481-1494
Articles

M. Mahmood Hussain
Jan 1, 2003; 44:22-32
Reviews

Expert

Centrioles are key eukaryotic organelles that are responsible for the formation of cilia and flagella, and for organizing the microtubule network and the mitotic spindle in animals. Centriole assembly requires oligomerization of the essential protein spindle assembly abnormal 6 (SAS-6), which forms a structural scaffold templating the organization of further organelle components. A dimerization interaction between SAS-6 N-terminal “head” domains was previously shown to be essential for protein oligomerization in vitro and for function in centriole assembly. Here, we developed a pharmacophore model allowing us to assemble a library of low-molecular-weight ligands predicted to bind the SAS-6 head domain and inhibit protein oligomerization. We demonstrate using NMR spectroscopy that a ligand from this family binds at the head domain dimerization site of algae, nematode, and human SAS-6 variants, but also that another ligand specifically recognizes human SAS-6. Atomistic molecular dynamics simulations starting from SAS-6 head domain crystallographic structures, including that of the human head domain which we now resolve, suggest that ligand specificity derives from favorable Van der Waals interactions with a hydrophobic cavity at the dimerization site.

A. V. Domrina
Trans. Moscow Math. Soc. 83 (), 201-215.
Abstract, references and article information

China Paves Its Way in New Areas of International Law Expert comment sysadmin 31 March 2017

China is looking to increase its capacity and influence in international legal matters – and it is particularly in frontier areas of the law that China is likely to take a proactive stance.

Foreign Minister Wang Yi called China a staunch defender and builder of the international rule of law in his speech to the UN General Assembly in October 2014. He promised that as China grew stronger, it would make a greater contribution to the maintenance and promotion of international rule of law, and would work with other countries to build a fairer and more reasonable international political and economic order.

For many in China, that time has now come: there is a sense that China deserves a much stronger and more respected voice in discussions surrounding the future of the international system. The recent speeches of Xi Jinping in Davos and Geneva in January 2017 suggest that China is now seizing the initiative and fighting for a voice and influence commensurate with its status and power as the number two economy in the world.

But there is an interesting divide in the areas in which China chooses to assert itself. In traditional areas of international law – such as the law of the sea and international human rights law – China continues to harbour reservations about the fairness of the existing international order. Its misgivings are fuelled by a perception that it did not play a significant part in the creation of the post-Second World War international order, and that those rules operate mainly in the interests of Western powers.

There is also a sense that traditional areas of international law do not offer a level playing field for China, since Western states have far more experience at operating in those. We know from Chinese experts that in the South China Sea case, one background issue that played into China’s refusal to engage in litigation with the Philippines and other interested states (which were represented by leading Western international lawyers) was a lack of experience before international courts and tribunals.

Contrast this with newer areas of international law– such as the regimes governing cyber, space, climate change and deep sea mining issues. In these areas, the rules are still in the process of being developed and tested, and the influence of the existing powers is not so firmly established or accepted, so there is more opportunity for China’s voice to be heard and heeded.

On climate change, China has become a champion of the Paris Agreement, which it worked hard with the Obama administration to secure. China is also active in some of the processes related to cyber rule-making, both as a member of the UN Group of Governmental Experts on cyber issues and through bilateral dialogues with a number of states. China has taken a keen interest in the regime applicable to the mining of the international seabed, making submissions to the International Tribunal on the Law of the Sea about the procedure for settling disputes. In international economic law, another relatively new area, China has been assiduously cultivating expertise, and is a major player in the negotiation of the ‘mega regional’ trade deal, the Regional Comprehensive Economic Partnership.

In time, the development of China’s much heralded Belt and Road Initiative may provide an opportunity for China to be further involved in international norm-setting, through the creation of a system of economic and political interaction that is built and run more along Chinese determined lines. The emergence of the Asian Infrastructure Investment Bank may offer an early indicator of China’s attempts to shape global governance, although in this context China has so far scrupulously observed international standards and has made no open attempt to challenge them.

So far, China’s practical input to international norm-setting has been limited. While China is prone to making wide-ranging statements of principle, it finds it more challenging to engage in the nitty gritty of specific rule making. But as is clear from its membership of the WTO, China can adapt quickly. While initially it was a reluctant adherent to the WTO dispute settlement mechanism, China is now adept at making active and effective use of its rules to promote China’s interests, including launching a legal challenge regarding the contested issue of its non-market economy status. Overall, there is strong leadership backing for a more activist approach to its engagement with the international legal system.

China sees international law as an important instrument in the “toolbox” of international diplomacy. It will increasingly be seeking to leverage international law to promote its own interests, particularly in newer areas, as it seeks to strengthen its wider soft power and influence.

‘Hong Kong is now in the hands of its people – they cannot rely on others to stick up for them now.’ Expert comment sysadmin 29 June 2017

Kerry Brown on ‘one country, two systems’, the UK’s diminishing influence and the territory’s future, 20 years after the handover.

1 July marks the 20th anniversary of the transfer of Hong Kong’s sovereignty from Britain to China. Kerry Brown speaks with Jason Naselli about what the future holds for the territory.

How sustainable is the ‘one country, two systems’ framework? Will the arrangement last the full 50 years (until 2047) as originally envisioned?

It is questionable whether the arrangement that exists today was the one envisioned in 1997 when the handover happened. It was always a very abstract, flexible system, granting Hong Kong a high degree of autonomy, meaning it could maintain its capitalist system. Of course, in the lead up to 1997 all these things were broadly seen as being in Beijing’s interests to preserve.

But these days, the one thing that few said in 1997 has come to pass – the People’s Republic has maintained one-party rule as a political system, but become one of the world’s great economies. It has been so far a huge success.

Hong Kong therefore has diminished in importance over the years to the point that maintaining at least some semblance of one country, two systems is almost like an act of charity. It has been nibbled at, compromised and seems to grow weaker by the day. Most in Hong Kong would say there is a system: one country, one system. That’s the deal.

The central government’s deepening involvement in the territory’s politics is a subject of growing controversy in Hong Kong. Does the Chinese government need to alter its approach?

Not particularly. It doesn’t want to see Hong Kong fail as an economy. That doesn’t suit its interests at all. But nor does it want a truculent, disobedient polity that is meant to be part of its sovereign territory.

So it has increasingly set political parameters. Hong Kong can have its unique system – as long as it is obedient. And on the whole, that is the deal that all of the city’s chief executives until now have internally understood perfectly.

As part of the 1997 handover, the UK has ‘a continuing moral and political obligation’ to Hong Kong. How will this relationship play out as Brexit shifts Britain’s place in the world?

The Foreign Office offers a six-monthly report to Parliament, updating on how the handover deal is going. As the years go on, however, it becomes increasingly illusive how the UK has any real locus to say much about the situation on Hong Kong. It did say, rightly, that the detainment of one of the booksellers taken in in 2015 was a violation of the treaty because he was British. This was the strongest wording that has ever appeared from an official British source. But with dependence on creating a new kind of relationship with China now foremost in people’s minds because of Brexit and other economic pressures, it is not surprising that the priority increasingly lies elsewhere.

With direct management of Hong Kong gone, the UK was always going to be more and more irrelevant. That has happened. And in any case, relations with China have had to become more complex and multifaceted. Hong Kong was always the tail wagging the dog for the UK relations with China. Now there has been a rebalancing, the calculation always has to be how much unilaterally supporting Hong Kong will damage relations with Beijing. This has become an increasingly asymmetrical question: in a playoff, preserving links with Beijing will always prevail. That’s just the reality of the new world we are seeing come into being.

Hong Kong has played an important financial role for China over the past 20 years, but where will it fit as markets and financial institutions on the mainland mature?

It maintains is role as a major RMB hub, and as a finance centre. But it is surrounded by competition. Singapore, and Sydney, and other places in the region have RMB deals. Shanghai and Tianjin aspire to be portals for entry to the domestic Chinese market. Hong Kong every day has to think of new ways to maintain its relevance and beat back competition. So far, it has done well. But this is an issue it can never be complacent about.

What has been the most significant change in Hong Kong society since 1997?

The rising cultural and linguistic influence of the mainland on Hong Kong. Hong Kong has maintained its difference – but it has had to change. It is clear that Hong Kong is now in the hands of Hong Kongese – they cannot rely on others to stick up for them now. The culture, identity and future of the territory are in their hands. In that sense, they have autonomy.

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Jian Li
Proc. Amer. Math. Soc. 152 (), 5207-5217.
Abstract, references and article information

John D. Berman
Proc. Amer. Math. Soc. 152 (), 5055-5066.
Abstract, references and article information