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Enlarge / This is Apple’s Vision Pro headset. It looks a bit like a particularly bulky pair of ski goggles, with the materials and design language of Apple’s AirPods Max headphones. (credit: Samuel Axon)
Apple has been forced to make drastic cuts to production forecasts for the mixed-reality Vision Pro headset, unveiled last month after seven years in development and hailed as its most significant product launch since the iPhone.
The complexity of the headset design and difficulties in production are behind the scaling back of targets, while plans for a more affordable version of the device have had to be pushed back, according to multiple people with direct knowledge of the manufacturing process.
Apple has already flagged that the $3,500 “spatial computing” headset device will not go on sale until “early next year,” a lengthy gap from its June 5 launch. Analysts have interpreted this as being more to do with supply chain problems than allowing developers time to create apps for the Vision Pro.
Every person starts as just one fertilized egg. By adulthood, that single cell has turned into roughly 37 trillion cells, many of which keep dividing to create the same amount of fresh human cells every few months.
But those cells have a formidable challenge. The average dividing cell must copy—perfectly—3.2 billion base pairs of DNA, about once every 24 hours. The cell’s replication machinery does an amazing job of this, copying genetic material at a lickety-split pace of some 50 base pairs per second.
Still, that’s much too slow to duplicate the entirety of the human genome. If the cell’s copying machinery started at the tip of each of the 46 chromosomes at the same time, it would finish the longest chromosome—No. 1, at 249 million base pairs—in about two months.
“The way cells get around this, of course, is that they start replication in multiple spots,” says James Berger, a structural biologist at the Johns Hopkins University School of Medicine in Baltimore, who co-authored an article on DNA replication in eukaryotes in the 2021 Annual Review of Biochemistry. Yeast cells have hundreds of potential replication origins, as they’re called, and animals like mice and people have tens of thousands of them, sprinkled throughout their genomes.
“But that poses its own challenge,” says Berger, “which is, how do you know where to start, and how do you time everything?” Without precision control, some DNA might get copied twice, causing cellular pandemonium.
Keeping tight reins on the kickoff of DNA replication is particularly important to avoid that pandemonium. Today, researchers are making steps toward a full understanding of the molecular checks and balances that have evolved in order to ensure that each origin initiates DNA copying once and only once, to produce precisely one complete new genome.
Bad things can happen if replication doesn’t start correctly. For DNA to be copied, the DNA double helix must open up, and the resulting single strands—each of which serves as a template for building a new, second strand—are vulnerable to breakage. Or the process can get stuck. “You really want to resolve replication quickly,” says John Diffley, a biochemist at the Francis Crick Institute in London. Problems during DNA replication can cause the genome to become disorganized, which is often a key step on the route to cancer.
Some genetic diseases, too, result from problems with DNA replication. For example, Meier-Gorlin syndrome, which involves short stature, small ears, and small or no kneecaps, is caused by mutations in several genes that help to kick off the DNA replication process.
It takes a tightly coordinated dance involving dozens of proteins for the DNA-copying machinery to start replication at the right point in the cell’s life cycle. Researchers have a pretty good idea of which proteins do what, because they’ve managed to make DNA replication happen in cell-free biological mixtures in the lab. They’ve mimicked the first crucial steps in initiation of replication using proteins from yeast—the same kind used to make bread and beer—and they’ve mimicked much of the entire replication process using human versions of replication proteins, too.
The cell controls the start of DNA replication in a two-step process. The whole goal of the process is to control the actions of a crucial enzyme—called a helicase—that unwinds the DNA double helix in preparation for copying it. In the first step, inactive helicases are loaded onto the DNA at the origins, where replication starts. During the second step, the helicases are activated, to unwind the DNA.
Kicking off the process is a cluster of six proteins that sit down at the origins. Called ORC, this cluster is shaped like a double-layer ring with a handy notch that allows it to slide onto the DNA strands, Berger’s team has found.
In baker’s yeast, which is a favorite for scientists studying DNA replication, these start sites are easy to spot: They have a specific, 11- to 17-letter core DNA sequence, rich in adenine and thymine chemical bases. Scientists have watched as ORC grabs onto the DNA and then slides along, scanning for the origin sequence until it finds the right spot.
But in humans and other complex life forms, the start sites aren’t so clearly demarcated, and it’s not quite clear what makes the ORC settle down and grab on, says Alessandro Costa, a structural biologist at the Crick Institute who, with Diffley, wrote about DNA replication initiation in the 2022 Annual Review of Biochemistry. Replication seems more likely to start in places where the genome—normally tightly spooled around proteins called histones—has loosened up.
The initiation of DNA replication starts at the tail end of the previous cell division and continues through the cell cycle phase known as G1. DNA synthesis happens during the S phase. Levels of a protein called CDK are critical to ensuring that DNA is replicated once and only once. When CDK levels are low, helicases can jump onto the DNA and start to unwind it. But repeat binding does not happen because CDK levels rise, and this blocks the helicase from binding again. (credit: Knowable Magazine)
Once ORC has settled onto the DNA, it attracts a second protein complex: one that includes the helicase that will eventually unwind the DNA. Costa and colleagues used electron microscopy to work out how ORC lures in first one helicase, and then another. The helicases are also ring-shaped, and each one opens up to wrap around the double-stranded DNA. Then the two helicases close up again, facing toward each other on the DNA strands, like two beads on a string.
At first, they just sit there, like cars with no gas in the tank. They haven’t been activated yet, and for now the cell goes about its usual business.
Things kick into high gear when a crucial molecule called CDK waves the green flag, jump-starting chemical steps that lure in even more proteins. One of them is DNA polymerase—what Costa calls the “typewriter” that will build new DNA strands—which hitches onto each helicase. Others activate the helicases, which can now burn energy to chug along the DNA.
As this occurs, the helicases change shape, pushing on one DNA strand and pulling on the other. This creates strain on the weak hydrogen bonds that normally hold the two strands together by the bases—the As, Cs, Ts and Gs that make up the rungs of the DNA ladder. The two strands get ripped apart. Costa and colleagues have observed how the two helicases untwist the DNA between them, and they’ve seen how the helicases keep the unbound bases stable and out of the way.
Left: Several genes involved in the initiation of DNA replication (horizontal axis) are amplified—that is, mistakenly copied in extra numbers — to varying degrees (vertical axis) in different cancers. Right: On chromosome 8, a cluster of three genes—shown in green text—are frequently amplified together in certain cancers. (credit: Knowable Magazine)
At first, both helicases are wrapped around both strands of DNA, and they can’t get very far like this, because they are facing each other and will just run into each other. But next, they each undergo a change in position, spitting one DNA strand or the other out of the ring. Now separated, they can jostle past each other, and replication proceeds apace.
Each helicase motors along its single strand, in the opposite direction from the other. They leave the origin behind and yank apart those hydrogen-bonded base pairs as they travel. The DNA polymerase is right behind, copying the DNA letters as they’re freed from their partners.
CDK’s second job is to stop any more helicases from hopping on the origins. Thus, there is one start of replication per origin, ensuring proper copying of the genome—although copying doesn’t begin at the same time at each site. The whole process of DNA replication, in human cells, takes about eight hours.
There is still plenty to be worked out. For one thing, the DNA that’s being copied is not a naked double helix. It’s wrapped around histones and attached to lots of other proteins that are busy turning genes on or off or making RNA copies of the genes. How do those jostling proteins affect each other and avoid getting in each other’s way?
Beyond this fascinating, fundamental biology—a remarkable process essential for all life on Earth—there are implications for diseases like cancer. Scientists already know that faulty replication can destabilize DNA, and an unstable genome that’s prone to mutation may be an early hallmark of cancer development. And they are further investigating links between replication proteins and cancer.
“I think that there are opportunities for therapeutic interventions for these systems,” says Berger, “once we have enough insights about how they work and what they look like.”
Amber Dance, a science writer in the Los Angeles area, also likes to break large tasks into smaller segments: It took her five days to complete the steps to draft this article. This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews. Sign up for the newsletter.
Enlarge / An image of a cell under a lab microscope. This procedure was not related to the new experiment with monkey embryos. (credit: Getty Images)
The early days of how an embryo develops are shrouded in mystery, because it pulls a kind of vanishing act. Once a sperm finds an egg, it begins a roughly weeklong journey to the uterus, becoming a tiny ball of cells along the way. When it reaches its destination, it attaches to the wall of the uterus, disappearing from view.
To shed light on the process, researchers are trying to create embryo-like structures derived from stem cells, rather than sperm and eggs, so they can observe early development in the lab. These three-dimensional balls of cells could offer clues to how diseases, birth defects, and miscarriages arise, without the practical and ethical concerns raised by using actual embryos. In the latest effort, researchers in China made these structures using stem cells from macaques and tried to establish pregnancies with them in female monkeys. The experiment is described in the journal Cell Stem Cell. Although other researchers have created “synthetic” embryos before, it’s the first time anyone has done it with monkeys—animals closely related to humans—and tried to get them to implant in the uterus.
Enlarge (credit: Walter Zerla via Getty Images)
Say you are a maker of computer graphics cards, under pressure from investors questioning your green credentials. You know what to do. You email your various departments, asking them to tally up their carbon emissions and the energy they consume. Simple enough. You write a report pledging a more sustainable future, in which your trucks are electrified and solar panels adorn your offices.
Good start, your investors say. But what about the mines that produced the tantalum or palladium in your transistors? Or the silicon wafers that arrived via a lengthy supply chain? And what of when your product is shipped to customers, who install it in a laptop or run it 24/7 inside a data center to train an AI model like GPT-4 (or 5)? Eventually it will be discarded as trash or recycled. Chase down every ton of carbon and the emissions a company creates are many times times higher than it first seemed.
Enlarge / Magnified view of Vibrio vulnificus bacteria. (credit: Smith Collection/Gado via Getty Images)
Cases of a potentially fatal infection from a seawater-borne pathogen have increased off the US Atlantic coast as ocean waters warmed over the last 30 years and are expected to rise further in future because of climate change, according to a study published on Thursday by Scientific Reports, an open-access journal for research on the natural sciences and other topics.
The incidence of infections from Vibrio vulnificus, a pathogen that thrives in shallow, brackish water, was eight times greater in the Eastern US in 2018 than it was in 1988, and its range shifted northward to areas where waters were previously too cold to support it, according to the paper, “Climate Warming and Increasing Vibrio Vulnificus Infections in North America,” by academic researchers in the US, England, and Spain.
By the middle of the 21st century, the pathogen is expected to become more common in major population centers, including New York City, and by the end of the century, infections may be present in every US Atlantic coast state if carbon emissions follow a medium- to high-level trajectory, the report said.
Enlarge / Even hermit crabs have individual patterns of behavior — personalities, if you like. When scientists ignore the effects of such differences, they may produce research that’s flawed. (credit: NurPhoto via Getty Images)
Several years ago, Christian Rutz started to wonder whether he was giving his crows enough credit. Rutz, a biologist at the University of St. Andrews in Scotland, and his team were capturing wild New Caledonian crows and challenging them with puzzles made from natural materials before releasing them again. In one test, birds faced a log drilled with holes that contained hidden food, and could get the food out by bending a plant stem into a hook. If a bird didn’t try within 90 minutes, the researchers removed it from the dataset.
But, Rutz says, he soon began to realize he was not, in fact, studying the skills of New Caledonian crows. He was studying the skills of only a subset of New Caledonian crows that quickly approached a weird log they’d never seen before—maybe because they were especially brave, or reckless.
The team changed its protocol. They began giving the more hesitant birds an extra day or two to get used to their surroundings, then trying the puzzle again. “It turns out that many of these retested birds suddenly start engaging,” Rutz says. “They just needed a little bit of extra time.”
Enlarge (credit: Edward Olive/Getty Images)
ChatGPT might well be the most famous, and potentially valuable, algorithm of the moment, but the artificial intelligence techniques used by OpenAI to provide its smarts are neither unique nor secret. Competing projects and open source clones may soon make ChatGPT-style bots available for anyone to copy and reuse.
Stability AI, a startup that has already developed and open-sourced advanced image-generation technology, is working on an open competitor to ChatGPT. “We are a few months from release,” says Emad Mostaque, Stability’s CEO. A number of competing startups, including Anthropic, Cohere, and AI21, are working on proprietary chatbots similar to OpenAI’s bot.
Enlarge / Signage outside Silicon Valley Bank headquarters in Santa Clara, California, US, on Thursday, March 9, 2023. SVB Financial Group bonds are plunging alongside its shares after the company moved to shore up capital after losses on its securities portfolio and a slowdown in funding. Photographer: David Paul Morris/Bloomberg via Getty Images (credit: Bloomberg via Getty Images)
Silicon Valley Bank was shuttered by US regulators on Friday after a rush of deposit outflows and a failed effort to raise new capital called into question the future of the tech-focused lender.
With about $209 billion in assets, SVB has become the second-largest bank failure in US history after the 2008 collapse of Washington Mutual, and marks a swift fall from grace for a lender that was valued at more than $44 billion less than 18 months ago.
The Federal Deposit Insurance Corporation, the US regulator that guarantees bank deposits of up to $250,000, said it was closing SVB and that insured depositors would have access to their funds by Monday.
Enlarge / Employees work on an assembly line in the mobile phone plant of Rising Stars Mobile India Pvt., a unit of Foxconn Technology Co., in Sriperumbudur, Tamil Nadu, India, on Friday, July 12, 2019. (credit: Bloomberg via Getty Images)
Apple and its manufacturing partner Foxconn were among the companies behind a landmark liberalization of labor laws in the Indian state of Karnataka last month, according to three people familiar with the matter.
Their successful lobbying for new legislation means two-shift production can take place in India, akin to the two companies’ practices in China, their primary manufacturing base. The law gives the southern state one of the most flexible working regimes in India as the country aims to become an alternative manufacturing base to China.
Karnataka’s move is an attempt to seize the opportunity created by companies that are seeking to end an over reliance on Chinese manufacturing, following months of COVID-19 disruption that has shaken global supply chains.
Enlarge / Photo taken in Florence, Italy (credit: Daniele Ciabatti/EyeEm via Getty)
When Mark Necaise got down to his last four floppy disks at a rodeo in Mississippi in February, he started to worry.
Necaise travels to horse shows around the state, offering custom embroidery on jackets and vests: “All of the winners would get a jacket and we’d put the name of the farm or the name of the horse or whatever on it,” he says.
Five years ago, he paid $18,000 for a second-hand machine, manufactured in 2004 by the Japanese embroidery equipment specialist Tajima. The only way to transfer the designs from his computer to the machine was via floppy disk.
Enlarge (credit: Anadolu via Getty Images)
It has been more than a decade since Jeff Bezos excitedly sketched out his vision for Alexa on a whiteboard at Amazon’s headquarters. His voice assistant would help do all manner of tasks, such as shop online, control gadgets, or even read kids a bedtime story.
But the Amazon founder’s grand vision of a new computing platform controlled by voice has fallen short. As hype in the tech world turns feverishly to generative AI as the “next big thing,” the moment has caused many to ask hard questions of the previous “next big thing”—the much-lauded voice assistants from Amazon, Google, Apple, Microsoft, and others.
A “grow grow grow” culture described by one former Amazon Alexa marketing executive has now shifted to a more intense focus on how the device can help the e-commerce giant make money.
Enlarge (credit: Jeffrey Coolidge/Getty Images)
Since the invasion of Ukraine one year ago, Russia has faced an exodus of tech companies and services. This includes the exit of Samsung and Apple, two of the world’s most popular smartphone brands. In response, the country has doubled down on its efforts to attain technological self-sufficiency, including creating a new Android smartphone.
The handset, which does not yet have a name, will be built by the National Computer Corporation (NCC), one of Russia’s largest IT companies, with an ambitious goal to sell 100,000 smartphones and tablets by the end of 2023. Alexander Kalinin, the founder of NCC, told local media on Monday that he aims to invest 10 billion rubles ($132.9 million) in the project and hopes to capture 10 percent of the consumer market by 2026.
The news comes just days after the US Department of Commerce banned exports to Russia of phones and other electronics that cost more than $300. Experts say, however, that a Russian smartphone will have a hard time beating inexpensive competitors from China, and it may encounter problems with using Google’s Android.
Enlarge / Asian woman with protective face mask using smartphone while commuting in the urban bridge in city against crowd of people (credit: d3sign via Getty Images)
On March 28, 2020, as COVID-19 cases began to shut down public life in much of the United States, then-Surgeon General Jerome Adams issued an advisory on Twitter: The general public should not wear masks. “There is scant or conflicting evidence they benefit individual wearers in a meaningful way,” he wrote.
Adams’ advice was in line with messages from other US officials and the World Health Organization. Days later, though, US public health leaders shifted course. Mask-wearing was soon a pandemic-control strategy worldwide, but whether this strategy succeeded is now a matter of heated debate—particularly after a major new analysis, released in January, seemed to conclude that masks remain an unproven strategy for curbing transmission of COVID-19 and other respiratory viruses.
“There’s still no evidence that masks are effective during a pandemic,” the study’s lead author, physician, and epidemiologist Tom Jefferson, recently told an interviewer.
Enlarge (credit: James Marshall / Getty Images)
David Wakeling, head of London-based law firm Allen & Overy's markets innovation group, first came across law-focused generative AI tool Harvey in September 2022. He approached OpenAI, the system’s developer, to run a small experiment. A handful of his firm’s lawyers would use the system to answer simple questions about the law, draft documents, and take first passes at messages to clients.
The trial started small, Wakeling says, but soon ballooned. Around 3,500 workers across the company’s 43 offices ended up using the tool, asking it around 40,000 queries in total. The law firm has now entered into a partnership to use the AI tool more widely across the company, though Wakeling declined to say how much the agreement was worth. According to Harvey, one in four at Allen & Overy’s team of lawyers now uses the AI platform every day, with 80 percent using it once a month or more. Other large law firms are starting to adopt the platform too, the company says.
The rise of AI and its potential to disrupt the legal industry has been forecast multiple times before. But the rise of the latest wave of generative AI tools, with ChatGPT at its forefront, has those within the industry more convinced than ever.
(credit: Flickr user LNG0004)
A human player has comprehensively defeated a top-ranked AI system at the board game Go, in a surprise reversal of the 2016 computer victory that was seen as a milestone in the rise of artificial intelligence.
Kellin Pelrine, an American player who is one level below the top amateur ranking, beat the machine by taking advantage of a previously unknown flaw that had been identified by another computer. But the head-to-head confrontation in which he won 14 of 15 games was undertaken without direct computer support.
The triumph, which has not previously been reported, highlighted a weakness in the best Go computer programs that is shared by most of today’s widely used AI systems, including the ChatGPT chatbot created by San Francisco-based OpenAI.
Enlarge / German police officers sit in their vehicle at the Neuenburg junction of the A5 motorway and observe the traffic from France. (credit: Philipp von Ditfurth/Getty Images)
Britta Eder’s list of phone contacts is full of people the German state considers to be criminals. As a defense lawyer in Hamburg, her client list includes anti-fascists, people who campaign against nuclear power, and members of the PKK, a banned militant Kurdish nationalist organization.
For her clients’ sake, she’s used to being cautious on the phone. “When I talk on the phone I always think, maybe I'm not alone,” she says. That self-consciousness even extends to phone calls with her mother.
Enlarge (credit: David McNew/Getty Images)
In a huge hangar in Quonset Point, Rhode Island, welders are aiming blazing torches at sheets of aluminum. The hulls of three new ships, each about 27 meters long, are taking shape. The first will hit the water sometime in the spring, ferrying workers to service wind turbines off the New England coast.
The US barely has an offshore wind sector for these vessels to service. But as the Biden administration accelerates a plan to decarbonize its power generation sector, turbines will sprout along its coastline, creating demand for services in shipyards and manufacturing hubs from Brownsville, Texas, to Albany, New York.
Senesco Marine, the shipbuilder in Rhode Island, has almost doubled its workforce in recent months as new orders for hybrid ferries and larger crew transfer vessels have come in. “Everybody tells me recession in America is inevitable,” says Ted Williams, a former US Navy officer who is now the company’s chief executive. “But it’s not happening in shipbuilding.”
This week, Argentina and Uruguay declared national health emergencies following outbreaks of highly pathogenic avian influenza H5N1, the fast-moving virus that destroys poultry flocks and wild birds and for decades has been feared as a possible spark for a pandemic among people. That makes 10 South American countries that have recently marked their first-ever encounter with the virus, including Peru—where more than 50,000 wild birds died last fall, and more than 600 sea lions in January. Combine the sea-lion infections with the revelation that H5N1 flu invaded a mink farm in Spain in October, and health authorities must now confront the possibility that the unpredictable virus may have adapted to threaten other species.
To be clear, this does not yet include people. Although past decades have witnessed bird flu outbreaks that spread to humans, only two cases have been identified in the past 12 months: a Colorado adult last May, and a 9-year-old girl in Ecuador in January. (Neither died.) And there’s no evidence yet that the virus has been able to jump from newly infected mammals to people. But the fact that it was transmitted from birds to mammals, and then spread among them, indicates a disquieting trend.
Enlarge / The Milky Way's Galactic Center and Jupiter (brightest spot at center top) are seen from the countryside near the small town of Rebolledo, Department of Florida, Uruguay in August 2020. (credit: Mariana Suarez/Getty Images)
Humans are naturally afraid of the dark. We sometimes imagine monsters under the bed and walk faster down unlit streets at night. To conquer our fears, we may leave a night light on to scare away the monsters and a light over the porch to deter break-ins.
Yet, in huddling for safety under our pools of light, we have lost our connection to the night sky. Star counts by public awareness campaign Globe at Night revealed that, between 2011 and 2022, the world’s night sky more than doubled in artificial brightness. Yet local interventions can create meaningful change.
Light pollution is cutting us off from one of nature’s greatest wonders, harming wildlife and blocking research that could help fight climate change. Stars are more than pretty glimmers in the night sky. They have shaped the mythology of every human civilization. They guide birds on their astonishing migratory journeys. And now we need to do our bit to prevent light pollution so stars can be part of our future.
Enlarge / A man fills the tank of his car with hydrogen at a station of the Ad Astra Rocket Company in Guanacaste, Costa Rica, on January 19, 2022. Former astronaut Franklin Chang is confident that in 10 years Costa Rica, his country, will be different. He hopes it will be much richer and cleaner, a product of green hydrogen technology, which he has been researching and developing since 2011. (credit: Ezequiel Becerra/AFP via Getty Images)
Franklin Chang-Díaz gets into his car, turns on the radio, and hears the news about another increase in the price of gasoline. But he sets off knowing that his trip won’t be any more expensive: His tank is filled with hydrogen. His car takes that element and combines it with oxygen in a fuel cell that works like a small power plant, creating energy—which goes into a battery to power the car—and water vapor. Not only will Chang-Díaz’s trip cost no more than it did yesterday, it will also pollute far less than a traditional gasoline-powered car would.
Chang-Díaz would like to have a public hydrogen station nearby whenever he needs to fill his tank, but that isn’t possible yet, either in his native Costa Rica or in any other Latin American country. He ends up instead at the hydrogen station he built himself, as part of a project aimed at demonstrating that hydrogen generated with renewable energy sources—green hydrogen—is the present, not the future.
A physicist, former NASA astronaut, and the CEO of Ad Astra Rocket Company, Chang-Díaz has a clear vision. Green hydrogen, he believes, is a fundamental player in lowering emissions from transportation and converting regions that import fossil fuels—such as his small Central American country—into exporters of clean energy, key to avoiding the catastrophic effects of global warming.
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