The orexigenic gut peptide ghrelin is an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHSR1a). Systemic ghrelin administration has previously been shown to increase gastric motility and emptying. While these effects are known to be mediated by the vagus nerve, the cellular mechanism underlying these effects remains unclear. Therefore, the purpose of the present study was to investigate the signaling mechanism by which GHSR1a inhibits voltage-gated Ca²⁺ channels in isolated rat gastric vagal afferent neurons using whole-cell patch-clamp electrophysiology. The ghrelin pharmacological profile indicated that Ca²⁺ currents were inhibited with a log (Ic₅₀) = –2.10 ± 0.44 and a maximal inhibition of 42.8 ± 5.0%. Exposure to the GHSR1a receptor antagonist (D-Lys3)-GHRP-6 reduced ghrelin-mediated Ca²⁺ channel inhibition (29.4 ± 16.7% vs. 1.9 ± 2.5%, n = 6, P = 0.0064). Interestingly, we observed that activation of GHSR1a inhibited Ca²⁺ currents through both voltage-dependent and voltage-independent pathways. We also treated the gastric neurons with either pertussis toxin (PTX) or YM-254890 to examine whether the Ca²⁺ current inhibition was mediated by the Gα_i/o or Gα_q/11 family of subunits. Treatment with both PTX (Ca²⁺ current inhibition = 15.7 ± 10.6%, n = 8, P = 0.0327) and YM-254890 (15.2 ± 11.9%, n = 8, P = 0.0269) blocked ghrelin’s effects on Ca²⁺ currents, as compared with control neurons (34.3 ± 18.9%, n = 8). These results indicate GHSR1a can couple to both Gα_i/o and Gα_q/11 in gastric vagal afferent neurons. Overall, our findings suggest GHSR1a-mediated inhibition of Ca²⁺ currents occurs through two distinct pathways, offering necessary insights into the cellular mechanisms underlying ghrelin’s regulation of gastric vagal afferents.

SIGNIFICANCE STATEMENT

This study demonstrated that in gastric vagal afferent neurons, activation of GHSR1a by ghrelin inhibits voltage-gated Ca²⁺ channels through both voltage-dependent and voltage-independent signaling pathways. These results provide necessary insights into the cellular mechanism underlying ghrelin regulation of gastric vagal afferent activity, which may benefit future studies investigating ghrelin mimetics to treat gastric motility disorders.

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions. Fatty acid binding protein 5 (FABP5) is a lipid chaperone highly expressed in macrophages. FABP5 deletion is implicated in driving macrophages toward an anti-inflammatory phenotype, yet signaling pathways regulated by macrophage-FABP5 have not been systematically profiled. We leveraged proteomic and phosphoproteomic approaches to characterize pathways modulated by FABP5 in M1 and M2 polarized bone marrow-derived macrophages (BMDMs). Stable isotope labeling by amino acids-based analysis of M1 and M2 polarized wild-type and FABP5 knockout BMDMs revealed numerous differentially regulated proteins and phosphoproteins. FABP5 deletion impacted downstream pathways associated with inflammation, cytokine production, oxidative stress, and kinase activity. Toll-like receptor 2 (TLR2) emerged as a novel target of FABP5 and pharmacological FABP5 inhibition blunted TLR2-mediated activation of downstream pathways, ascribing a novel role for FABP5 in TLR2 signaling. This study represents a comprehensive characterization of the impact of FABP5 deletion on the proteomic and phosphoproteomic landscape of M1 and M2 polarized BMDMs. Loss of FABP5 altered pathways implicated in inflammatory responses, macrophage function, and TLR2 signaling. This work provides a foundation for future studies seeking to investigate the therapeutic potential of FABP5 inhibition in pathophysiological states resulting from dysregulated inflammatory signaling.

SIGNIFICANCE STATEMENT

This research offers a comprehensive analysis of fatty acid binding protein 5 (FABP5) in macrophages during inflammatory response. The authors employed quantitative proteomic and phosphoproteomic approaches to investigate this utilizing bone marrow-derived macrophages that were M1 and M2 polarized using lipopolysaccharide with interferon and interleukin-4, respectively. This revealed multiple pathways related to inflammation that were differentially regulated due to the absence of FABP5. These findings underscore the potential therapeutic significance of macrophage-FABP5 as a candidate for addressing inflammatory-related diseases.

Practicing family medicine is really hard; the emotional toll of sharing patients’ distress, vulnerability, and trauma can build up and become overwhelming. A family physician experienced such a moment during one particularly complex morning. Feeling nearly ready to walk out of patient care, she reached out to the team nurse, who helped her get through the moment and re-engage with the waiting patients. Sharing vulnerability in the moment, and later reflecting and deciding to write about it shows the power of prioritizing teamwork in practice.

The driverless vehicles still can't take L.A.'s notorious highways.

It's a slightly quieter week after the mass dump of games that was February and the first week of March. Kelley doesn't want her mom to think she's watching hentai, while Anna Marie insists our reviewers don't hate every game. Josh will one day be free of the epic grip of Cold Steel IV, but not before Chris convinces him if he just lifts a truck, he can find a new orbment.

The post RPG Cast – Episode 577: “Eclipse, I Love You, but GO AWAY” appeared first on RPGamer.

Jonathan Stringer joins us in an attempt to sell his copy of Mugen Souls. Josh is launching his Kickstarter for his new documentary, Legacy of the Bitcoins. And Chris has lost his Epic Games launcher, thanks Windows 11.

The post RPG Cast – Episode 616: “Garland Does It His Way” appeared first on RPGamer.

Kelley is a complicated person when it comes to PC gaming. Josh is a quiet English man, slightly constipated. And Chris takes a Steam Deck to the face.

The post RPG Cast – Episode 649: “Away With You, Stadia!” appeared first on RPGamer.

Chris launches his new brand, Elsa coffee. Kelley's Pokémon demand she finds a caramel apple and a teacup. Ryan apparently got left in Seattle and is still at PAX West.

The post RPG Cast – Episode 693: “The Brew Never Bothered Me Anyways” appeared first on RPGamer.

Chris kink-shames Red XIII. Kelley violates the time space continuum with cat cafes. Josh is better at keeping things afloat than Embracer Group. Robert fails at being family friendly.

The post RPG Cast – Episode 711: “I’ve Always Wanted a Gaming Napkin” appeared first on RPGamer.

The mystery surrounding Deadlock, Valve’s work-in-progress MOBA shooter, has largely evaporated. Its freely extendable invite system is about as effective at controlling player headcount as a disinterested football steward, meaning pretty much anyone with a clued-in Steam friend can get in and start poking around its secrets. And yet, being a lane-pushing wizard fighter in the Dota 2 vein, it’s already a vast tangle of interplaying abilities, items, strats, and often unspoken rules, of the kind that even experienced gankists will take hundreds of hours to learn. It’s been too much for poor Brendy, at any rate.

Still, Brendy is but one man. What if we had but four men, working in tandem to crush lanes and flatten Patrons just as Gabe intended? To find out if Deadlock is indeed more comprehensible as a team sport, Graham, Ed, Ollie, and James joined forces, promptly getting fucked up yet emerging from the warlock hospital with a deeper understanding of its workings. Or, at least, if anyone would keep playing.

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I first played Taiko no Tatsujin in an arcade (in Japan, because I am very cool), where it's controlled by hitting a recreation of an actual taiko drum. It was fun enough that I wish there was a taiko drum peripheral available for PC now the series is on our platform.

Taiko no Tatsujin: Rhythm Festival is out now via Steam, where it offers over 70 songs to drum through, and a subscription service through which to unlock over 700 more. Maybe I should try to get my Donkey Konga drums working on PC, but I'll probably settle for playing it with a gamepad.

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Astronomers have identified patterns within the motion of stars stretching across the Milky Way, hinting at the presence of a vast wave

Astronomers have detected an exoplanet around Barnard’s star, one of the sun’s closest neighbours, but it is too hot for liquid water or life

Dangerous radiation reaches Mars at levels we aren't exposed to on Earth, which makes the Red Planet a particularly dangerous place to be during pregnancy

Roads with variable speed limits, designed to manage traffic flow, are normally adjusted according to simple rules, but a 27-kilometre section of the I-24 freeway near Nashville, Tennessee, is now overseen by an artificial intelligence

Google has built a quantum computer that makes fewer errors as it is scaled up, and this may pave the way for machines that could solve useful real-world problems for the first time

NASA’s Valkyrie is undergoing tests to understand what it would take to get a humanoid robot onto offshore facilities or into space. New Scientist's James Woodford took the controls to see what it is capable of

A new way to store numbers in computers can dynamically prioritise accuracy or range, depending on need, allowing software to quickly switch between very large and small numbers

I have a confession to make. After taking a handful of autonomous taxi rides, I have gone from a hater to a friend of robot cars in just a few weeks, says Annalee Newitz

Hollywood has been imagining the impact AI might have on our lives for decades, but how accurate are these portrayals?

More than 80 per cent of B.C.'s water basins are experiencing level 4 or 5 drought conditions, with salmon in many parts of the province struggling to make it to their spawning grounds.

DNA from mitochondria, the energy powerhouses inside cells, sometimes gets added to our genome – and the number of these mutations in the brain could be linked to ageing

A better understanding of what happens to our bodies when we get fitter can unlock ways to speed up the journey – and it might be simpler than you think

A chemical produced by gut bacteria could be the basis for a non-invasive test for endometriosis – and mouse experiments suggest it might also help treat the condition

Imagine pulling up to a refueling station and filling your vehicle’s tank with liquid hydrogen, as safe and convenient to handle as gasoline or diesel, without the need for high-pressure tanks or cryogenic storage. This vision of a sustainable future could become a reality if a Calgary, Canada–based company, Ayrton Energy, can scale up its innovative method of hydrogen storage and distribution. Ayrton’s technology could make hydrogen a viable, one-to-one replacement for fossil fuels in existing infrastructure like pipelines, fuel tankers, rail cars, and trucks.

The company’s approach is to use liquid organic hydrogen carriers (LOHCs) to make it easier to transport and store hydrogen. The method chemically bonds hydrogen to carrier molecules, which absorb hydrogen molecules and make them more stable—kind of like hydrogenating cooking oil to produce margarine.

A researcher pours a sample of Ayrton’s LOHC fluid into a vial.Ayrton Energy

The approach would allow liquid hydrogen to be transported and stored in ambient conditions, rather than in the high-pressure, cryogenic tanks (to hold it at temperatures below -252 ºC) currently required for keeping hydrogen in liquid form. It would also be a big improvement on gaseous hydrogen, which is highly volatile and difficult to keep contained.

Founded in 2021, Ayrton is one of several companies across the globe developing LOHCs, including Japan’s Chiyoda and Mitsubishi, Germany’s Covalion, and China’s Hynertech. But toxicity, energy density, and input energy issues have limited LOHCs as contenders for making liquid hydrogen feasible. Ayrton says its formulation eliminates these trade-offs.

Safe, Efficient Hydrogen Fuel for Vehicles

Conventional LOHC technologies used by most of the aforementioned companies rely on substances such as toluene, which forms methylcyclohexane when hydrogenated. These carriers pose safety risks due to their flammability and volatility. Hydrogenious LOHC Technologies in Erlanger, Germany and other hydrogen fuel companies have shifted toward dibenzyltoluene, a more stable carrier that holds more hydrogen per unit volume than methylcyclohexane, though it requires higher temperatures (and thus more energy) to bind and release the hydrogen. Dibenzyltoluene hydrogenation occurs at between 3 and 10 megapascals (30 and 100 bar) and 200–300 ºC, compared with 10 MPa (100 bar), and just under 200 ºC for methylcyclohexane.

Ayrton’s proprietary oil-based hydrogen carrier not only captures and releases hydrogen with less input energy than is required for other LOHCs, but also stores more hydrogen than methylcyclohexane can—55 kilograms per cubic meter compared with methylcyclohexane’s 50 kg/m³. Dibenzyltoluene holds more hydrogen per unit volume (up to 65 kg/m³), but Ayrton’s approach to infusing the carrier with hydrogen atoms promises to cost less. Hydrogenation or dehydrogenation with Ayrton’s carrier fluid occurs at 0.1 megapascal (1 bar) and about 100 ºC, says founder and CEO Natasha Kostenuk. And as with the other LOHCs, after hydrogenation it can be transported and stored at ambient temperatures and pressures.

Judges described [Ayrton's approach] as a critical technology for the deployment of hydrogen at large scale.” —Katie Richardson, National Renewable Energy Lab

Ayrton’s LOHC fluid is as safe to handle as margarine, but it’s still a chemical, says Kostenuk. “I wouldn’t drink it. If you did, you wouldn’t feel very good. But it’s not lethal,” she says.

Kostenuk and fellow Ayrton cofounder Brandy Kinkead (who serves as the company’s chief technical officer) were originally trying to bring hydrogen generators to market to fill gaps in the electrical grid. “We were looking for fuel cells and hydrogen storage. Fuel cells were easy to find, but we couldn’t find a hydrogen storage method or medium that would be safe and easy to transport to fuel our vision of what we were trying to do with hydrogen generators,” Kostenuk says. During the search, they came across LOHC technology but weren’t satisfied with the trade-offs demanded by existing liquid hydrogen carriers. “We had the idea that we could do it better,” she says. The duo pivoted, adjusting their focus from hydrogen generators to hydrogen storage solutions.

“Everybody gets excited about hydrogen production and hydrogen end use, but they forget that you have to store and manage the hydrogen,” Kostenuk says. Incompatibility with current storage and distribution has been a barrier to adoption, she says. “We’re really excited about being able to reuse existing infrastructure that’s in place all over the world.” Ayrton’s hydrogenated liquid has fuel-cell-grade (99.999 percent) hydrogen purity, so there’s no advantage in using pure liquid hydrogen with its need for subzero temperatures, according to the company.

The main challenge the company faces is the set of issues that come along with any technology scaling up from pilot-stage production to commercial manufacturing, says Kostenuk. “A crucial part of that is aligning ourselves with the right manufacturing partners along the way,” she notes.

Asked about how Ayrton is dealing with some other challenges common to LOHCs, Kostenuk says Ayrton has managed to sidestep them. “We stayed away from materials that are expensive and hard to procure, which will help us avoid any supply chain issues,” she says. By performing the reactions at such low temperatures, Ayrton can get its carrier fluid to withstand 1,000 hydrogenation-dehydrogenation cycles before it no longer holds enough hydrogen to be useful. Conventional LOHCs are limited to a couple of hundred cycles before the high temperatures required for bonding and releasing the hydrogen breaks down the fluid and diminishes its storage capacity, Kostenuk says.

Breakthrough in Hydrogen Storage Technology

In acknowledgement of what Ayrton’s nontoxic, oil-based carrier fluid could mean for the energy and transportation sectors, the U.S. National Renewable Energy Lab (NREL) at its annual Industry Growth Forum in May named Ayrton an “outstanding early-stage venture.” A selection committee of more than 180 climate tech and cleantech investors and industry experts chose Ayrton from a pool of more than 200 initial applicants, says Katie Richardson, group manager of NREL’s Innovation and Entrepreneurship Center, which organized the forum. The committee based its decision on the company’s innovation, market positioning, business model, team, next steps for funding, technology, capital use, and quality of pitch presentation. “Judges described Ayrton’s approach as a critical technology for the deployment of hydrogen at large scale,” Richardson says.

As a next step toward enabling hydrogen to push gasoline and diesel aside, “we’re talking with hydrogen producers who are right now offering their customers cryogenic and compressed hydrogen,” says Kostenuk. “If they offered LOHC, it would enable them to deliver across longer distances, in larger volumes, in a multimodal way.” The company is also talking to some industrial site owners who could use the hydrogenated LOHC for buffer storage to hold onto some of the energy they’re getting from clean, intermittent sources like solar and wind. Another natural fit, she says, is energy service providers that are looking for a reliable method of seasonal storage beyond what batteries can offer. The goal is to eventually scale up enough to become the go-to alternative (or perhaps the standard) fuel for cars, trucks, trains, and ships.

Every invention begins with a problem—and the creative act of seeing a problem where others might just see unchangeable reality. For one 5-year-old, the problem was simple: She liked to have her tummy rubbed as she fell asleep. But her mom, exhausted from working two jobs, often fell asleep herself while putting her daughter to bed. “So [the girl] invented a teddy bear that would rub her belly for her,” explains Stephanie Couch, executive director of the Lemelson MIT Program. Its mission is to nurture the next generation of inventors and entrepreneurs.

Anyone can learn to be an inventor, Couch says, given the right resources and encouragement. “Invention doesn’t come from some innate genius, it’s not something that only really special people get to do,” she says. Her program creates invention-themed curricula for U.S. classrooms, ranging from kindergarten to community college.

We’re biased, but we hope that little girl grows up to be an engineer. By the time she comes of age, the act of invention may be something entirely new—reflecting the adoption of novel tools and the guiding forces of new social structures. Engineers, with their restless curiosity and determination to optimize the world around them, are continuously in the process of reinventing invention.

In this special issue, we bring you stories of people who are in the thick of that reinvention today. IEEE Spectrum is marking 60 years of publication this year, and we’re celebrating by highlighting both the creative act and the grindingly hard engineering work required to turn an idea into something world changing. In these pages, we take you behind the scenes of some awe-inspiring projects to reveal how technology is being made—and remade—in our time.

Inventors Are Everywhere

Invention has long been a democratic process. The economist B. Zorina Khan of Bowdoin College has noted that the U.S. Patent and Trademark Office has always endeavored to allow essentially anyone to try their hand at invention. From the beginning, the patent examiners didn’t care who the applicants were—anyone with a novel and useful idea who could pay the filing fee was officially an inventor.

This ethos continues today. It’s still possible for an individual to launch a tech startup from a garage or go on “Shark Tank” to score investors. The Swedish inventor Simone Giertz, for example, made a name for herself with YouTube videos showing off her hilariously bizarre contraptions, like an alarm clock with an arm that slapped her awake. The MIT innovation scholar Eric von Hippel has spotlighted today’s vital ecosystem of “user innovation,” in which inventors such as Giertz are motivated by their own needs and desires rather than ambitions of mass manufacturing.

But that route to invention gets you only so far, and the limits of what an individual can achieve have become starker over time. To tackle some of the biggest problems facing humanity today, inventors need a deep-pocketed government sponsor or corporate largess to muster the equipment and collective human brainpower required.

When we think about the challenges of scaling up, it’s helpful to remember Alexander Graham Bell and his collaborator Thomas Watson. “They invent this cool thing that allows them to talk between two rooms—so it’s a neat invention, but it’s basically a gadget,” says Eric Hintz, a historian of invention at the Smithsonian Institution. “To go from that to a transcontinental long-distance telephone system, they needed a lot more innovation on top of the original invention.” To scale their invention, Hintz says, Bell and his colleagues built the infrastructure that eventually evolved into Bell Labs, which became the standard-bearer for corporate R&D.

In this issue, we see engineers grappling with challenges of scale in modern problems. Consider the semiconductor technology supported by the U.S. CHIPS and Science Act, a policy initiative aimed at bolstering domestic chip production. Beyond funding manufacturing, it also provides US $11 billion for R&D, including three national centers where companies can test and pilot new technologies. As one startup tells the tale, this infrastructure will drastically speed up the lab-to-fab process.

And then there are atomic clocks, the epitome of precision timekeeping. When researchers decided to build a commercial version, they had to shift their perspective, taking a sprawling laboratory setup and reimagining it as a portable unit fit for mass production and the rigors of the real world. They had to stop optimizing for precision and instead choose the most robust laser, and the atom that would go along with it.

These technology efforts benefit from infrastructure, brainpower, and cutting-edge new tools. One tool that may become ubiquitous across industries is artificial intelligence—and it’s a tool that could further expand access to the invention arena.

What if you had a team of indefatigable assistants at your disposal, ready to scour the world’s technical literature for material that could spark an idea, or to iterate on a concept 100 times before breakfast? That’s the promise of today’s generative AI. The Swiss company Iprova is exploring whether its AI tools can automate “eureka” moments for its clients, corporations that are looking to beat their competitors to the next big idea. The serial entrepreneur Steve Blank similarly advises young startup founders to embrace AI’s potential to accelerate product development; he even imagines testing product ideas on digital twins of customers. Although it’s still early days, generative AI offers inventors tools that have never been available before.

Measuring an Invention’s Impact

If AI accelerates the discovery process, and many more patentable ideas come to light as a result, then what? As it is, more than a million patents are granted every year, and we struggle to identify the ones that will make a lasting impact. Bryan Kelly, an economist at the Yale School of Management, and his collaborators made an attempt to quantify the impact of patents by doing a technology-assisted deep dive into U.S. patent records dating back to 1840. Using natural language processing, they identified patents that introduced novel phrasing that was then repeated in subsequent patents—an indicator of radical breakthroughs. For example, Elias Howe Jr.’s 1846 patent for a sewing machine wasn’t closely related to anything that came before but quickly became the basis of future sewing-machine patents.

Another foundational patent was the one awarded to an English bricklayer in 1824 for the invention of Portland cement, which is still the key ingredient in most of the world’s concrete. As Ted C. Fishman describes in his fascinating inquiry into the state of concrete today, this seemingly stable industry is in upheaval because of its heavy carbon emissions. The AI boom is fueling a construction boom in data centers, and all those buildings require billions of tons of concrete. Fishman takes readers into labs and startups where researchers are experimenting with climate-friendly formulations of cement and concrete. Who knows which of those experiments will result in a patent that echoes down the ages?

Some engineers start their invention process by thinking about the impact they want to make on the world. The eminent Indian technologist Raghunath Anant Mashelkar, who has popularized the idea of “Gandhian engineering”, advises inventors to work backward from “what we want to achieve for the betterment of humanity,” and to create problem-solving technologies that are affordable, durable, and not only for the elite.

Durability matters: Invention isn’t just about creating something brand new. It’s also about coming up with clever ways to keep an existing thing going. Such is the case with the Hubble Space Telescope. Originally designed to last 15 years, it’s been in orbit for twice that long and has actually gotten better with age, because engineers designed the satellite to be fixable and upgradable in space.

For all the invention activity around the globe—the World Intellectual Property Organization says that 3.5 million applications for patents were filed in 2022—it may be harder to invent something useful than it used to be. Not because “everything that can be invented has been invented,” as in the apocryphal quote attributed to the unfortunate head of the U.S. patent office in 1889. Rather, because so much education and experience are required before an inventor can even understand all the dimensions of the door they’re trying to crack open, much less come up with a strategy for doing so. Ben Jones, an economist at Northwestern’s Kellogg School of Management, has shown that the average age of great technological innovators rose by about six years over the course of the 20th century. “Great innovation is less and less the provenance of the young,” Jones concluded.

Consider designing something as complex as a nuclear fusion reactor, as Tom Clynes describes in “An Off-the-Shelf Stellarator.” Fusion researchers have spent decades trying to crack the code of commercially viable fusion—it’s more akin to a calling than a career. If they succeed, they will unlock essentially limitless clean energy with no greenhouse gas emissions or meltdown danger. That’s the dream that the physicists in a lab in Princeton, N.J., are chasing. But before they even started, they first had to gain an intimate understanding of all the wrong ways to build a fusion reactor. Once the team was ready to proceed, what they created was an experimental reactor that accelerates the design-build-test cycle. With new AI tools and unprecedented computational power, they’re now searching for the best ways to create the magnetic fields that will confine the plasma within the reactor. Already, two startups have spun out of the Princeton lab, both seeking a path to commercial fusion.

The stellarator story and many other articles in this issue showcase how one innovation leads to the next, and how one invention can enable many more. The legendary Dean Kamen, best known for mechanical devices like the Segway and the prosthetic “Luke” arm, is now trying to push forward the squishy world of biological manufacturing. In an interview, Kamen explains how his nonprofit is working on the infrastructure—bioreactors, sensors, and controls—that will enable companies to explore the possibilities of growing replacement organs. You could say that he’s inventing the launchpad so others can invent the rockets.

Sometimes everyone in a research field knows where the breakthrough is needed, but that doesn’t make it any easier to achieve. Case in point: the quest for a household humanoid robot that can perform domestic chores, switching effortlessly from frying an egg to folding laundry. Roboticists need better learning software that will enable their bots to navigate the uncertainties of the real world, and they also need cheaper and lighter actuators. Major advances in these two areas would unleash a torrent of creativity and may finally bring robot butlers into our homes.

And maybe the future roboticists who make those breakthroughs will have cause to thank Marina Umaschi Bers, a technologist at Boston College who cocreated the ScratchJr programming language and the KIBO robotics kit to teach kids the basics of coding and robotics in entertaining ways. She sees engineering as a playground, a place for children to explore and create, to be goofy or grandiose. If today’s kindergartners learn to think of themselves as inventors, who knows what they’ll create tomorrow?

Research expeditions conducted at sea using a rotating gravity machine and microscope found that the Earth’s oceans may not be absorbing as much carbon as researchers have long thought.

Oceans are believed to absorb roughly 26 percent of global carbon dioxide emissions by drawing down CO₂ from the atmosphere and locking it away. In this system, CO₂ enters the ocean, where phytoplankton and other organisms consume about 70 percent of it. When these organisms eventually die, their soft, small structures sink to the bottom of the ocean in what looks like an underwater snowfall.

This “marine snow” pulls carbon away from the surface of the ocean and sequesters it in the depths for millennia, which enables the surface waters to draw down more CO₂ from the air. It’s one of Earth’s best natural carbon-removal systems. It’s so effective at keeping atmospheric CO₂ levels in check that many research groups are trying to enhance the process with geoengineering techniques.

But the new study, published on 11 October in Science, found that the sinking particles don’t fall to the ocean floor as quickly as researchers thought. Using a custom gravity machine that simulated marine snow’s native environment, the study’s authors observed that the particles produce mucus tails that act like parachutes, putting the brakes on their descent—sometimes even bringing them to a standstill.

The physical drag leaves carbon lingering in the upper hydrosphere, rather than being safely sequestered in deeper waters. Living organisms can then consume the marine snow particles and respire their carbon back into the sea. Ultimately, this impedes the rate at which the ocean draws down and sequesters additional CO₂ from the air.

The implications are grim: Scientists’ best estimates of how much CO₂ the Earth’s oceans sequester could be way off. “We’re talking roughly hundreds of gigatonnes of discrepancy if you don’t include these marine snow tails,” says Manu Prakash, a bioengineer at Stanford University and one of the paper’s authors. The work was conducted by researchers at Stanford, Rutgers University in New Jersey, and Woods Hole Oceanographic Institution in Massachusetts.

Oceans Absorb Less CO₂ Than Expected

Researchers for years have been developing numerical models to estimate marine carbon sequestration. Those models will need to be adjusted for the slower sinking speed of marine snow, Prakash says.

The findings also have implications for startups in the fledgling marine carbon geoengineering field. These companies use techniques such as ocean alkalinity enhancement to augment the ocean’s ability to sequester carbon. Their success depends, in part, on using numerical models to prove to investors and the public that their techniques work. But their estimates are only as good as the models they use, and the scientific community’s confidence in them.

“We’re talking roughly hundreds of gigatonnes of discrepancy if you don’t include these marine snow tails.” —Manu Prakash, Stanford University

The Stanford researchers made the discovery on an expedition off the coast of Maine. There, they collected marine samples by hanging traps from their boat 80 meters deep. After pulling up a sample, the researchers quickly analyzed the contents while still on board the ship using their wheel-shaped machine and microscope.

The researchers built a microscope with a spinning wheel that simulates marine snow falling through sea water over longer distances than would otherwise be practical.Prakash Lab/Stanford

The device simulates the organisms’ vertical travel over long distances. Samples go into a wheel about the size of a vintage film reel. The wheel spins constantly, allowing suspended marine-snow particles to sink while a camera captures their every move.

The apparatus adjusts for temperature, light, and pressure to emulate marine conditions. Computational tools assess flow around the sinking particles and custom software removes noise in the data from the ship’s vibrations. To accommodate for the tilt and roll of the ship, the researchers mounted the device on a two-axis gimbal.

Slower Marine Snow Reduces Carbon Sequestration

With this setup, the team observed that sinking marine snow generates an invisible halo-shaped comet tail made of viscoelastic transparent exopolymer—a mucus-like parachute. They discovered the invisible tail by adding small beads to the seawater sample in the wheel, and analyzing the way they flowed around the marine snow. “We found that the beads were stuck in something invisible trailing behind the sinking particles,” says Rahul Chajwa, a bioengineering postdoctoral fellow at Stanford.

The tail introduces drag and buoyancy, doubling the amount of time marine snow spends in the upper 100 meters of the ocean, the researchers concluded. “This is the sedimentation law we should be following,” says Prakash, who hopes to get the results into climate models.

The study will likely help models project carbon export—the process of transporting CO₂ from the atmosphere to the deep ocean, says Lennart Bach, a marine biochemist at the University of Tasmania in Australia, who was not involved with the research. “The methodology they developed is very exciting and it’s great to see new methods coming into this research field,” he says.

But Bach cautions against extrapolating the results too far. “I don’t think the study will change the numbers on carbon export as we know them right now,” because these numbers are derived from empirical methods that would have unknowingly included the effects of the mucus tail, he says.

Marine snow may be slowed by “parachutes” of mucus while sinking, potentially lowering the rate at which the global ocean can sequester carbon in the depths.Prakash Lab/Stanford

Prakash and his team came up with the idea for the microscope while conducting research on a human parasite that can travel dozens of meters. “We would make 5- to 10-meter-tall microscopes, and one day, while packing for a trip to Madagascar, I had this ‘aha’ moment,” says Prakash. “I was like: Why are we packing all these tubes? What if the two ends of these tubes were connected?”

The group turned their linear tube into a closed circular channel—a hamster wheel approach to observing microscopic particles. Over five expeditions at sea, the team further refined the microscope’s design and fluid mechanics to accommodate marine samples, often tackling the engineering while on the boat and adjusting for flooding and high seas.

In addition to the sedimentation physics of marine snow, the team also studies other plankton that may affect climate and carbon-cycle models. On a recent expedition off the coast of Northern California, the group discovered a cell with silica ballast that makes marine snow sink like a rock, Prakash says.

The crafty gravity machine is one of Prakash’s many frugal inventions, which include an origami-inspired paper microscope, or “foldscope,” that can be attached to a smartphone, and a paper-and-string biomedical centrifuge dubbed a “paperfuge.”

From the busy cities to ocean waters, our need to illuminate the world has had some strange and tragic consequences

Organizing business events can be a challenge. There’s always the concern that guests will lose interest or become disengaged. When organizing team-building activities and office parties, it becomes essential to add something extra that keeps everyone active and involved. That way, the event not only meets expectations but exceeds them, leaving people excited and talking […]

The post 4 Creative Ways to Keep Guests Engaged at Your Next Business Event appeared first on Chart Attack.

1. Bypolls LIVE: Voting begins for Wayanad LS seat and 31 Assembly seats in 10 States; Priyanka Gandhi makes debut  The Hindu
2. Priyanka Gandhi's Debut, Bypolls In 31 Assembly Seats: All You Need To Know  NDTV
3. Watch: Rahul Gandhi tries Kerala's longest zipline in bid to promote tourism after landslides  The Times of India
4. Let's ensure resounding victory together: Rahul to Wayanad voters  The Hindu
5. Hope people of Wayanad give me chance to represent them, says Priyanka Gandhi  Telegraph India

Nolan has set up his much-awaited ‘Oppenheimer’ follow-up at Universal Pictures, eyeing a mid-2026 IMAX release 

His significant contributions to horror cinema led to his recognition with a Lifetime Achievement Award at the New York City Horror Film Festival

South Korean actor Song Jae Rim, known for his roles in popular K-Dramas, passed away at 39 in Seoul

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For the first time in over two years, Overwatch 2 players will be able to group up in teams of six. A three-week event featuring that format starts tomorrow, November 12. But there’s a twist: you won’t be able to select Kiriko or Sombra, or battle it out with an additional player on each side on Push maps just yet. That’s because in Overwatch 2’s first real taste of 6v6, Blizzard is taking us all the way back to the beginning with a limited-time mode called Overwatch: Classic.

You will be able to experience Overwatch almost exactly as it was upon its May 2016 debut. That means you can choose from the first 21 heroes, who all have their original kits and abilities. That means Hanzo loses his Lunge jump but regains his dreaded Scatter Arrow, Bastion and Torbjorn are vastly different than they are now and Cassidy's Flashbang once again stun locks enemies for a moment. 

Symmetra reverts to being a support who can teleport allies almost anywhere on the map from the spawn room, while Mercy can will once again bring five dead teammates back to life. Ultimate abilities will charge up faster too.

In addition, just like in Overwatch for a brief period at the very beginning, there are initially no limits on hero selection. So if you and your teammates want to run with a composition of four Winstons and two Lucios, have at it. However, this will only apply for the first few days, after which Blizzard will apply the single hero limit rule for the rest of the event. Games will take place under the Quick Play ruleset, rather than the Competitive format.

The original 12 maps will be available too — including the assault maps that Blizzard retired from the main modes during the transition to Overwatch 2. While assault maps are still available in the Arcade and custom games, you'll once again be dealing with the notorious choke points of the otherwise gorgeous Hanamura, Temple of Anubis and Volskaya Industries.

Blizzard Entertainment

Things won't be exactly as they were in May 2016, however. Original maps that have seen major reworks over the years — Dorado, Numbani, Route 66 and Watchpoint: Gibraltar — will appear as they are in the current game. You'll only be able to use the original default Overwatch skins and no, there are no loot boxes. The user interface remains the same too, which hopefully means the ping system will still be in place.

Blizzard doesn't plan for this to be a one-and-done deal. There will be other Overwatch: Classic events in the future, focusing on various moments in the game's history, like the infamous triple-tank, triple-support GOATS meta. This limited-time mode is also separate from the other 6v6 tests Blizzard plans to run in the coming months as it looks to measure players' interest in that format and garner feedback.

There's a good chance that this limited-time mode will bring some lapsed players back into the mix, even just for a sip of nostalgia. I first played Overwatch several months after its debut, so it'll be fun to see roughly how the game felt at the very beginning. I will be instalocking Mei every match so I can remember what it's like to freeze an opponent before giving them a cheeky wave and firing an icicle into their skull. Ah, memories...

This article originally appeared on Engadget at https://www.engadget.com/gaming/an-overwatch-classic-event-will-take-fans-all-the-way-back-to-the-beginning-171538261.html?src=rss

Waymo has announced expanded availability of its driverless rideshare service throughout Los Angeles. That’s right. Waymo One is now available to all customers anywhere in LA county, which is 80 square miles. The company has dropped the waitlist for area residents. Now LA residents will get to experience sitting in endless traffic with a series of cameras and navigational algos leading the way instead of a person.

This expanded service starts today and it offers “fully autonomous rides” at any time of the day or night. Let’s hear it for some drunken late night bonding with an algorithm. Waymo also says it’ll further expand the service area in the future. After all, Los Angeles comprises five counties. 

It’s been offering driverless rides to LA customers for a while now, but with a mandatory waitlist. Waymo One also started small in San Francisco and Phoenix before announcing similar expansions. The service will be coming to Austin and Atlanta in the near future.

All told, the company says over 300,000 Los Angeles residents have joined the waitlist for the service and Waymo One has completed “hundreds of thousands of paid trips across the city.” Waymo says these driverless rides are also highly rated, with an average rating of 4.7 stars out of five. A recent survey indicated that 98 percent of customers are satisfied with the service.

This article originally appeared on Engadget at https://www.engadget.com/transportation/waymos-driverless-cars-in-la-county-are-now-available-to-everyone-173237519.html?src=rss

FIRST came the smash, now comes the grab. It’s the crime wave that will send terror into the heart of every cafe owner worried that their stock standard breakfast basic is under threat of extinction.

Must-have gadgets and accessories for savvy travellers.

“Children are not small adults.” We invoke this saying, in a vague and hand-wavy manner, whenever we talk about the need to study drugs in pediatric populations. It’s an interesting idea, but it really cries out for further elaboration. If they’re not small adults, what are they? Are pediatric efficacy and safety totally uncorrelated with adult efficacy and safety? Or are children actually kind of like small adults in certain important ways?

Pediatric post-marketing studies have been completed for over 200 compounds in the years since BPCA (2002, offering a reward of 6 months extra market exclusivity/patent life to any drug conducting requested pediatric studies) and PREA (2007, giving FDA power to require pediatric studies) were enacted. I think it is fair to say that at this point, it would be nice to have some sort of comprehensive idea of how FDA views the risks associated with treating children with medications tested only on adults. Are they in general less efficacious? More? Is PK in children predictable from adult studies a reasonable percentage of the time, or does it need to be recharacterized with every drug?

Essentially, my point is that BPCA/PREA is a pretty crude tool: it is both too broad in setting what is basically a single standard for all new adult medications, and too vague as to what exactly that standard is.

In fact, a 2008 published review from FDA staffers and a 2012 Institute of Medicine report both show one clear trend: in a significant majority of cases, pediatric studies resulted in validating the adult medication in children, mostly with predictable dose and formulation adjustments (77 of 108 compounds (71%) in the FDA review, and 27 of 45 (60%) in the IOM review, had label changes that simply reflected that use of the drug was acceptable in younger patients).

So, it seems, most of the time, children are in fact not terribly unlike small adults.

But it’s also true that the percentages of studies that show lack of efficacy, or bring to light a new safety issue with the drug’s use in children, is well above zero. There is some extremely important information here.

To paraphrase John Wanamaker: we know that half our PREA studies are a waste of time; we just don’t know which half.

This would seem to me to be the highest regulatory priority – to be able to predict which new drugs will work as expected in children, and which may truly require further study. After a couple hundred compounds have gone through this process, we really ought to be better positioned to understand how certain pharmacological properties might increase or decrease the risks of drugs behaving differently than expected in children. Unfortunately, neither the FDA nor the IOM papers venture any hypotheses about this – both end up providing long lists of examples of certain points, but not providing any explanatory mechanisms that might enable us to engage in some predictive risk assessment.

While FDASIA did not advance PREA in terms of more rigorously defining the scope of pediatric requirements (or, better yet, requiring FDA to do so), it did address one lingering concern by requiring that FDA publish non-compliance letters for sponsors that do not meet their commitments. (PREA, like FDAAA, is a bit plagued by lingering suspicions that it’s widely ignored by industry.)

The first batch of letters and responses has been published, and it offers some early insights into the problems engendered by the nebulous nature of PREA and its implementation.

These examples, unfortunately, are still a bit opaque – we will need to wait on the FDA responses to the sponsors to see if some of the counter-claims are deemed credible. In addition, there are a few references to prior deferral requests, but the details of the request (and rationales for the subsequent FDA denials) do not appear to be publicly available. You can read FDA’s take on the new postings on their blog, or in the predictably excellent coverage from Alec Gaffney at RAPS.

Looking through the first 4 drugs publicly identified for noncompliance, the clear trend is that there is no trend. All these PREA requirements have been missed for dramatically different reasons.

Here’s a quick rundown of the drugs at issue – and, more interestingly, the sponsor responses:

1. Renvela - Genzyme (full response)

Genzyme appears to be laying responsibility for the delay firmly at FDA’s feet here, basically claiming that FDA continued to pile on new requirements over time:

Genzyme’s correspondence with the FDA regarding pediatric plans and design of this study began in 2006 and included a face to face meeting with FDA in May 2009. Genzyme submitted 8 revisions of the pediatric study design based on feedback from FDA including that received in 4 General Advice Letters. The Advice Letter dated February 17, 2011  contained further recommendations on the study design, yet still required the final clinical study report  by December 31, 2011.

This highlights one of PREA’s real problems: the requirements as specified in most drug approval letters are not specific enough to fully dictate the study protocol. Instead, there is a lot of back and forth between the sponsor and FDA, and it seems that FDA does not always fully account for their own contribution to delays in getting studies started.

2. Hectorol - Genzyme (full response)

In this one, Genzyme blames the FDA not for too much feedback, but for none at all:

On December 22, 2010, Genzyme submitted a revised pediatric development plan (Serial No. 212) which was intended to address FDA feedback and concerns that had been received to date. This submission included proposed protocol HECT05310. [...] At this time, Genzyme has not received feedback from the FDA on the protocol included in the December 22, 2010 submission.

If this is true, it appears extremely embarrassing for FDA. Have they really not provided feedback in over 2.5 years, and yet still sending noncompliance letters to the sponsor? It will be very interesting to see an FDA response to this.

3. Cleviprex – The Medicines Company (full response)

This is the only case where the pharma company appears to be clearly trying to game the system a bit. According to their response:

Recognizing that, due to circumstances beyond the company’s control, the pediatric assessment could not be completed by the due date, The Medicines Company notified FDA in September 2010, and sought an extension. At that time, it was FDA’s view that no extensions were available. Following the passage of FDASIA, which specifically authorizes deferral extensions, the company again sought a deferral extension in December 2012. 

So, after hearing that they had to move forward in 2010, the company promptly waited 2 years to ask for another extension. During that time, the letter seems to imply that they did not try to move the study forward at all, preferring to roll the dice and wait for changing laws to help them get out from under the obligation.

4. Twinject/Adrenaclick – Amedra (full response)

The details of this one are heavily redacted, but it may also be a bit of gamesmanship from the sponsor. After purchasing the injectors, Amedra asked for a deferral. When the deferral was denied, they simply asked for the requirements to be waived altogether. That seems backwards, but perhaps there's a good reason for that.

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Life can sometimes feel like a never-ending cycle of stress and decisions. That's usually my weekdays in a nutshell: chasing deadlines, making tough calls, and hopping between meetings. When your brain feels like it's on overdrive, it's time to hit pause. Engaging in some therapeutic activities can give your mind the breather it desperately needs. The good news? They don't have to be complicated or time-consuming. Here are some that can work wonders for your mental clarity and overall well-being. Step outside for a walk Walking is one of the simplest ways to clear your mind. It's amazing what a little fresh air at your nearby PCN can do. Just stepping outside and getting those legs moving can shift your perspective in a matter of minutes — and burn a few calories too! Disconnect from your phone and enjoy the sights and sounds of the great outdoors. I find that a 30-min walk and a change of environment works wonders for me, helping me rationally dissect my worries, such as my crushing feelings of inadequacy at work.

This cable contains information which we hope will be useful to you in engaging host governments, media, and the public after the President's address.

The bottom line is that Pakistan cannot afford the $2 billion required to complete this F-16 program.