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Testosterone May Protect Against Asthma

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Asthma, a disease of the lungs that causes inflammation, swelling, wheezing and shortness of breath, affects both sexes, but with one notable difference: Boys tend to grow out of asthma after puberty, and men are far less likely to develop it in adulthood than women are. Australian researchers explored the idea that testosterone may have a protective effect against asthma—and they believe it does, pinpointing some of the mechanisms by which it occurs. Their study results are published in the Journal of Experimental Medicine.

To understand testosterone’s effects, says co-lead author Gabrielle Belz, a professor of molecular immunology at the University of Melbourne, you must first understand a family of immune cells known as innate lymphoid cells, or ILC2s. These cells are found on various surfaces in the body: the lungs, gastrointestinal tract, and the skin, to name a few. “Their job is to sense what’s happening in the external environment and make adjustments based on that,” Belz tells Mental Floss. In asthma, these cells proliferate in high numbers and accumulate in the airways where they trigger chemicals, such as cytokines and leukocytes, “that promote that inflammatory response that results in the airways swelling [and] narrowing, and shortness of breath occurs,” she says.

Males have fewer of these cells than females, Belz says, “because the testosterone receptor regulates the generation of these cells.” Plus, the androgen receptors, whose job it is to sense testosterone, become activated in the presence of testosterone. This suppresses the generation of these ILC2 cells, though Belz and her team are still exploring the mechanism by which it does so. With fewer cells present, there are fewer pro-inflammatory signals—which explains why men are less likely to develop asthma.

To test these effects in mouse models, the researchers ran a number of different experiments, beginning with a baseline analysis of the tissues of healthy male and female mice. They found a significantly increased presence of ILC2s in female mice compared to males, specifically in the lungs of the female mice, where the frequencies and total numbers of ILC2s were “twofold higher” than in males.

In another experiment, the researchers tested the tissue of mice that had been genetically modified not to have the testosterone-sensing androgen receptors—essentially, these mice lacked the ability to suppress the ILC2 cells, making them more likely to have asthma symptoms. These mice showed ILC2 numbers comparable to female mice, as did castrated male mice. The castrated male mice “responded as intact females, indicating that endogenous male sex hormones act as critical regulators [of ILC2s],” the authors write in their paper.

They also took tissue from male and female mice that had been given ovalbumin-induced asthma, and found that there were higher numbers of inflammatory leukocytes in the female mice than in the males.

The mouse models suggest that testosterone is protective against asthma, so the next steps are to study human immune cells from blood samples in a dish. Scientists could expose the human cells to different mediators to stimulate the testosterone pathway. They can also implant the human cells into mouse models to get a more accurate understanding of how the human cells might function. “Our preclinical animal modes are surrogates for the situations that might occur in humans,” Belz says.

This is all well and good if you’re male, but if you’re female, or a prepubescent child, further research is needed to come up with a treatment for asthma. Hormones are crucial for the development and growth of the body, so they can’t simply give testosterone to women and children with asthma “because that could disrupt a whole heap of things in the body,” Belz says. What they hope to do next is to discover receptors in women and children that they can target, and to create synthetic molecules that function in the same way as testosterone—without the impact of a hormone.

If they can achieve a synthetic testosterone, they would ideally be able to formulate an inhaled drug that can be taken through an inhaler, similar to other drugs for lung-related diseases.

Delving into these kinds of differences in how the sexes respond to disease is part of a "big push in the field to have a personalized approach to medicine," says Belz. "So you’d have a slightly different approach to males or females to get on top of these diseases."

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iStock // Ekaterina Minaeva
Man Buys Two Metric Tons of LEGO Bricks; Sorts Them Via Machine Learning
May 21, 2017
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iStock // Ekaterina Minaeva

Jacques Mattheij made a small, but awesome, mistake. He went on eBay one evening and bid on a bunch of bulk LEGO brick auctions, then went to sleep. Upon waking, he discovered that he was the high bidder on many, and was now the proud owner of two tons of LEGO bricks. (This is about 4400 pounds.) He wrote, "[L]esson 1: if you win almost all bids you are bidding too high."

Mattheij had noticed that bulk, unsorted bricks sell for something like €10/kilogram, whereas sets are roughly €40/kg and rare parts go for up to €100/kg. Much of the value of the bricks is in their sorting. If he could reduce the entropy of these bins of unsorted bricks, he could make a tidy profit. While many people do this work by hand, the problem is enormous—just the kind of challenge for a computer. Mattheij writes:

There are 38000+ shapes and there are 100+ possible shades of color (you can roughly tell how old someone is by asking them what lego colors they remember from their youth).

In the following months, Mattheij built a proof-of-concept sorting system using, of course, LEGO. He broke the problem down into a series of sub-problems (including "feeding LEGO reliably from a hopper is surprisingly hard," one of those facts of nature that will stymie even the best system design). After tinkering with the prototype at length, he expanded the system to a surprisingly complex system of conveyer belts (powered by a home treadmill), various pieces of cabinetry, and "copious quantities of crazy glue."

Here's a video showing the current system running at low speed:

The key part of the system was running the bricks past a camera paired with a computer running a neural net-based image classifier. That allows the computer (when sufficiently trained on brick images) to recognize bricks and thus categorize them by color, shape, or other parameters. Remember that as bricks pass by, they can be in any orientation, can be dirty, can even be stuck to other pieces. So having a flexible software system is key to recognizing—in a fraction of a second—what a given brick is, in order to sort it out. When a match is found, a jet of compressed air pops the piece off the conveyer belt and into a waiting bin.

After much experimentation, Mattheij rewrote the software (several times in fact) to accomplish a variety of basic tasks. At its core, the system takes images from a webcam and feeds them to a neural network to do the classification. Of course, the neural net needs to be "trained" by showing it lots of images, and telling it what those images represent. Mattheij's breakthrough was allowing the machine to effectively train itself, with guidance: Running pieces through allows the system to take its own photos, make a guess, and build on that guess. As long as Mattheij corrects the incorrect guesses, he ends up with a decent (and self-reinforcing) corpus of training data. As the machine continues running, it can rack up more training, allowing it to recognize a broad variety of pieces on the fly.

Here's another video, focusing on how the pieces move on conveyer belts (running at slow speed so puny humans can follow). You can also see the air jets in action:

In an email interview, Mattheij told Mental Floss that the system currently sorts LEGO bricks into more than 50 categories. It can also be run in a color-sorting mode to bin the parts across 12 color groups. (Thus at present you'd likely do a two-pass sort on the bricks: once for shape, then a separate pass for color.) He continues to refine the system, with a focus on making its recognition abilities faster. At some point down the line, he plans to make the software portion open source. You're on your own as far as building conveyer belts, bins, and so forth.

Check out Mattheij's writeup in two parts for more information. It starts with an overview of the story, followed up with a deep dive on the software. He's also tweeting about the project (among other things). And if you look around a bit, you'll find bulk LEGO brick auctions online—it's definitely a thing!

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Name the Author Based on the Character
May 23, 2017
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