Tag Archives: Loud

For crying out loud: Dutch scientists grow human tear glands | Human biology

Stop your sobbing – because scientists can do it for you. Using stem cells, Dutch researchers have grown miniature human tear glands capable of “crying”.

Initially, when scientists were looking at developing this technology, their first port of call was the inner lining of the gut, because it replaces itself every five days. They took a tiny piece of gut tissue filled with stem cells and fed it proteins called growth factors to stimulate cell growth, expecting the stem cells to rapidly proliferate.

“But to our surprise, the stem cells created a mini-organ … it’s small, but it has all the different cells in the gut that you need for digesting food,” said the study author Hans Clevers, group leader at the Hubrecht Institute for developmental biology and stem cell research and at the Princess Máxima Center for pediatric oncology.

That was back in 2009. Since then, researchers have created mini versions – called organoids – of the liver, pancreas, bladder and more. They even moved from mammals to reptiles, successfully growing snake venom glands. Last year, Clevers’s PhD students elected to work on human tear glands.

After first successfully creating tear glands for mice, they moved on to human tissue. Suspended in a gel, the tiny piece of donated human tissue was given a cocktail of growth factors. After about a week, the researchers broke it up into small pieces and fed it some more to create several mini-glands. “They looked like little balloons,” said Clevers.

Tear glands are useful to their human host in a plethora of ways. They produce a thin layer of liquid that sheaths the cornea, lubricating the surface of the eye, protecting it from irritants and infections, and supplying nutrients. The glands are also responsible for manufacturing tears, whether due to physical provocation, say somebody sticks a nail in your eye, or emotional angst, caused by, for instance, a car that runs over your pet cat. In either case, the brain instructs the tear glands to weep.

“The chemical message that comes from the neurons … to your tear glands is adrenaline. So, to really show that we had functional tear glands, we needed to show that they would respond to adrenaline,” said Clevers.

When the mini-organs were given a persistent supply of the growth factor cocktail, they didn’t produce much tear fluid upon encountering adrenaline. But once they were cut off from the juice, the cells stopped dividing and were allowed to settle down and mature – the adrenaline quickly produced tears, he explained.

The little balloon-like glands rapidly got swollen because there were no ducts for the liquid to escape. Eventually, they were made to rupture or ruptured themselves, dribbling out some liquid in the form of droplets, added Clevers.

The model has some limitations. The researchers captured one cell – the ductal cell – that the tear gland is composed of, but the glands also comprise other cells. In addition, these organoids are not part of the human body – in which tear glands could be wrapped around by muscle and blood vessels – so there are limitations to their functioning, he cautioned.

“It is a reductionist model. But the essence of the tear gland is captured: namely, the tear formation and then the adrenaline-induced production of tear droplets.”

This model can now be used by researchers globally to identify new drugs for patients who do not produce enough tears and to study how cancers of the tear gland form and may be treated. Eventually, this type of organoid may even be transplantable to patients with non-functioning tear glands, the authors suggested in the journal Cell Stem Cell.

Meanwhile, researchers in Clevers’s lab already have their eye on their next project: crocodile tears.

“We want to grow crocodile tear glands,” said Clevers. “Crocodiles don’t cry because they’re sad or something; they’re just trying to get rid of salt. That’s why it’s scientifically interesting to really study how this works, how they use their tear glands as kidneys.”

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The Stick-Shift 668-HP CT5-V Blackwing And 472-HP Cadillac CT4-V Blackwing Are Cadillac’s Last Hurrah For Loud Gasoline Fury

Photo: David Tracy

This is the end. Cadillac, a brand with a rich history of stuffing gigantic gasoline motors under the hoods of luxury sedans, is about to call it quits on internal combustion, but not before going out with a bang. Well, two bangs, with one of them called the CT5-V Blackwing, a 668-horsepower 6.2-liter supercharged V8 sedan with a standard…standard transmission. The other is the CT4-V Blackwing, a smaller 472-HP twin-turbo 3.6-liter V6 sedan that also comes with a stick shift, in keeping with the car gods’ orders. Let’s take a first look at these last hurrahs for high-performance gasoline Cadillacs.

The auto industry is quickly entering the electric era, so it feels a bit strange for Cadillac to be debuting two entirely-conventional flagship sedans. But this is the last stand for performance gasoline Cadillacs, and my god is GM’s premium brand going out swinging.

So Much Power, So Many Pedals

Photo: David Tracy

The CT5-V is a 668-HP, 659 lb-ft supercharged V8 sedan with a six-speed manual transmission sending torque to the rear wheels. On paper, it is epic, fulfilling the entirety of Maslow’s Hierarchy of Automotive Needs (other than perhaps “low curb weight” the CT5-V Blackwing weighs roughly two tons). I can’t wait to drive this machine.

Photo: David Tracy

The other car Cadillac showed was the CT4-V, which also comes standard with a manual transmission, and also has a boosted engine that sends torque to the rear wheels, though that engine is a V6, and the high intake manifold air pressure comes from a pair of turbochargers instead of a supercharger.

Photo: David Tracy

Here’s a little walk-around of these two cars with marketing manager Ken Kornas:

When Cadillac released horsepower figures for the regular CT4-V and CT5-V, the automotive media pretty much spit out its drink and laughed. “We Regret To Inform You That The Cadillac CT4-V Has Just 24 More HP Than A Toyota Camry,” my colleague wrote after Jalopnik’s initial article titled “The 2020 Cadillac CT4-V and CT5-V Arrive Without The Big Power We’re Used To.”

After having been spoiled by the 464 HP ATS-V and 640 HP CTS-V, we just weren’t excited about the paltry 325 HP turbocharged inline-four in the CT4-V or the 360-HP twin-turbo V6 in the CT5-V. “Hey, this isn’t the real V, is it?” my Editor-in-Chief Rory Carroll asked Cadillac at an event in 2019. The brand responded that a “big V” was under development. Now it’s here along with its little sibling.

Photo: David Tracy

The 668-HP CT5-V Blackwing can allegedly pull off a 0-60 mph time of 3.7 seconds, and reach a top speed of over 200 mph. The 472-HP, 445 lb-ft CT4-V Blackwing takes a tenth more to get to 60, and its top speed plateaus at around 189 mph, per Cadillac. Both cars are built on the Alpha II platform, the successor to the Alpha platform that underpinned the Chevy Camaro and Cadillac ATS. Like the ATS and Camaro, the CT4 and CT5 have MacPherson strut front suspensions and five-link setups in the back.

Speaking of the ATS, the CT4-V Blackwing is likely going to be quite similar to that car’s V-model, which was an excellent driver’s car thanks to incredible steering feel and sharp handling. The CT4 has essentially the same engine and transmission, with roughly the same power (it’s up 8 HP). Car And Driver gets into the differences, writing in its story 472-HP 2022 Cadillac CT4-V Blackwing Is like an ATS-V, but Better:

Chassis upgrades include larger front and rear brake rotors, a newer version of the standard magnetorheological dampers, and Michelin Pilot Sport 4S tires instead of the old Pilot Super Sport rubber. These tires wrap around 18-inch wheels with a staggered-width setup; the magnesium wheels that Cadillac teased earlier won’t be available until later in the production run. The housing for the electronic limited-slip differential is now aluminum, which Cadillac says saves 22 pounds. Overall curb weight is up by a claimed 77 pounds.

Photo: David Tracy

I’m conflicted here, because as much as I love the idea of an improved ATS-V that handles well, the bigger, couple-of-hundred-pounds-heavier CT5-V Blackwing has the V8 with a 1.7-liter Eaton supercharger on it, and you know that’s going to sound much, much better. So the question is: Do you choose nimble(ish) handling or do you choose the glorious sound of a boosted V8?

Perhaps I’m a bit basic, but my initial primal instinct is to go with option B.

The Hardware

Photo: Cadillac

Cadillac didn’t have engineers at my preview session in a warehouse in Warren, Michigan, so the brand wasn’t able to get deep into the CT4-V Blackwing and CT5-V Blackwing’s tech. But right away, it was obvious how epic the cooling systems are unsurprising, given the ATS-V was a masterpiece in this area.

The cars each have roughly a dozen heat exchangers, with tiny outboards ones tilted, and angled a bit inboard:

Photo: David Tracy

My favorite heat exchanger (everyone should have a favorite heat exchanger, right?) on the CT4-V is the flat one up front, which I’m fairly sure cools the transmission and rear differential.

A heat exchanger whose face is actually parallel to airflow?! It seems counterintuitive, but it makes sense if you consider that it’s located just ahead of the main cooling module, which due to its restriction creates an area of high pressure ahead of itself. That high pressure, along with the low pressure under the vehicle as air rushes at a high velocity, forces air through the heat exchanger mounted parallel to the car’s floor:

Photo: David Tracy

While we’re on the topic of aerodynamics, Cadillac says the new grille design is a key enabler for improving airflow over the ATS-V, and the brand mentions a new Carbon Fiber Aero Package, which allegedly reduces lift by 214 percent on the CT4-V Blackwing and 75 percent on the CT5-V Blackwing. It goes without saying that there’s a drag penalty.

Also exciting are the underbody “airflow-channeling strakes” that make up what Cadillac calls the “Underwing” basically, an underbody airflow strategy that Cadillac says reduces drag and improves track performance:

Photo: David Tracy

Speaking of the underbody, here’s an “Easter Egg” V-Series logo at the bottom of the liquid-cooled electronic limited-slip differential:

Photo: David Tracy

The brakes are huge. The CT4-V Blackwing’s rotors are 15 inches up front and 13.4 out back, while the bigger sibling has 15.7-inch rotors ahead of the driver and 14.7s behind. Both cars have six-piston calipers at the nose and four-piston grabbers at the tail.

Photo: David Tracy

The standard manual transmission is a six-speed Tremec, with a dual-disk LuK clutch. In case you’re not familiar with how a twin-disc clutch works, it essentially involves bolting a housing to the flywheel, using axial space to create an additional surface for an additional clutch to grab onto. Here, watch this Aussie show you how it works:

Both cars get rev matching capability and “No-Lift Shift,” which is what it sounds like: You can stay hard on the accelerator pedal while shifting something that, per Cadillac, helps keep the CT4-V Blacking’s turbos in boost.

There’s also a 10-speed automatic available if you’re into that sort of thing.

Pricing

Photo: David Tracy

Photo: David Tracy

The CT4-V Blackwing starts at $59,990, while the CT5-V Blackwing costs $84,990. These are higher base prices than those of the Audi RS3 and BMW M3 with which GM says the two cars compete, respectively. How the Caddies will hold up on the track against their German counterparts is something I can’t wait to find out. Will Cadillac’s final internal combustion engine V-Series cars go out on top?

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