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Scientists Make Progress Toward a Safe, Effective Zika Vaccine

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A biologist releases genetically modified Aedes Egypti mosquitoes in Piracicaba, Brazil, in February 2016. The modified mosquitoes, which cannot transmit Zika, compete with wild mosquitoes. Image Credit: Victor Moriyama/Getty Images

Zika virus has spread to almost 60 countries since early 2016. Almost 5000 cases have been identified in the United States, including more than 200 infections transmitted in Florida and Texas. Though the virus often causes only mild symptoms (or may not cause any symptoms at all), the link between Zika infection, microcephaly, and other developmental abnormalities has been strengthened with additional studies over the past year. However, a vaccine is still unavailable.

New research led by investigators at the University of Pennsylvania may move us closer to the goal of a safe, effective vaccine for the virus. The findings were published today in the journal Nature.

The scientists used a novel type of vaccine to immunize mice and monkeys, taking RNA molecules that code for viral proteins (messenger RNA, or mRNA). Because these RNA molecules would usually be quickly cleared by the body, the RNA in the Zika vaccine was modified by the addition of a modified nucleoside. The nucleoside is a nucleotide—the building blocks of DNA—lacking a phosphate group, which previous studies have shown helps to “hide” the mRNA from the host and allow replication. The mRNA was also packaged within lipid nanoparticles, encouraging protein expression. This vaccine therefore allows the mRNA to enter cells and induce production of the viral protein, causing a host immune response similar to that seen with a live virus vaccine. Researchers found that a single dose of the mRNA vaccine effectively protected animals against Zika virus.

Senior author Drew Weissman, of the University of Pennsylvania, relayed the advantages of this approach in a phone call with mental_floss. “The main advantages of our RNA vaccine is that only a single administration is needed. For all of the DNA and inactivated vaccines, they have to immunize twice to get protection, so we get much higher levels of neutralization with a single immunization. The only other vaccine that had protection after a single immunization was the live virus adenovirus vaccine.”

Live vaccines are difficult for a number of reasons, including potential side effects, and cannot be used in pregnant women—a main risk group for Zika infections due to the virus’s effects on the developing fetus. Weissman also noted the mRNA vaccine is inexpensive to produce, which could facilitate widespread use even in resource-limited countries.

Scientists hope to start human clinical trials with the Zika mRNA vaccine in 12 to 18 months. In the interim, additional experiments are planned in order to begin studying whether this Zika vaccine could potentially lead to increased illness with a related flavivirus: dengue. Dengue infection can lead to a phenomenon called “antibody-dependent enhancement,” where antibodies make disease worse instead of protecting the host from infection. There is concern that those vaccinated for Zika could experience more severe dengue infections in areas where both viruses circulate.

To examine whether their Zika vaccine could cause this effect, Weissman says, “We’re taking two approaches. We want to look at antibody-dependent enhancement between different flaviviruses. We’re also working on a combination vaccine that includes all of the flavivirus RNAs together, and the hope there is that with a single vaccine we can immunize against Dengue, West Nile, Zika, Japanese encephalitis, or whatever flaviviruses we want to include.”

Weissman and his collaborators are not the only ones hoping to move a Zika vaccine from the lab to the clinic. A number of different groups have worked to develop a Zika vaccine over the last year. A Phase I clinical trial, to investigate vaccine safety, began last August of a DNA vaccine developed at the National Institutes of Health. And while investigators are hopeful that one of the vaccines in development could be ready for use by 2018, vaccines for pregnant women may be delayed until several years after that, due to the difficulties of demonstrating safety in that population.

The components of the mRNA vaccine also provide hope the vaccine could be used during pregnancy. Weissman explains, “The RNA they use is identical to what’s in our bodies. The nanoparticles also contain mostly physiological lipids. We’ve seen no adverse events from any of our immunizations, so we’re thinking that will probably be easy to give to a pregnant woman.”

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iStock // Ekaterina Minaeva
Man Buys Two Metric Tons of LEGO Bricks; Sorts Them Via Machine Learning
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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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One Bite From This Tick Can Make You Allergic to Meat
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We like to believe that there’s no such thing as a bad organism, that every creature must have its place in the world. But ticks are really making that difficult. As if Lyme disease wasn't bad enough, scientists say some ticks carry a pathogen that causes a sudden and dangerous allergy to meat. Yes, meat.

The Lone Star tick (Amblyomma americanum) mostly looks like your average tick, with a tiny head and a big fat behind, except the adult female has a Texas-shaped spot on its back—thus the name.

Unlike other American ticks, the Lone Star feeds on humans at every stage of its life cycle. Even the larvae want our blood. You can’t get Lyme disease from the Lone Star tick, but you can get something even more mysterious: the inability to safely consume a bacon cheeseburger.

"The weird thing about [this reaction] is it can occur within three to 10 or 12 hours, so patients have no idea what prompted their allergic reactions," allergist Ronald Saff, of the Florida State University College of Medicine, told Business Insider.

What prompted them was STARI, or southern tick-associated rash illness. People with STARI may develop a circular rash like the one commonly seen in Lyme disease. They may feel achy, fatigued, and fevered. And their next meal could make them very, very sick.

Saff now sees at least one patient per week with STARI and a sensitivity to galactose-alpha-1, 3-galactose—more commonly known as alpha-gal—a sugar molecule found in mammal tissue like pork, beef, and lamb. Several hours after eating, patients’ immune systems overreact to alpha-gal, with symptoms ranging from an itchy rash to throat swelling.

Even worse, the more times a person is bitten, the more likely it becomes that they will develop this dangerous allergy.

The tick’s range currently covers the southern, eastern, and south-central U.S., but even that is changing. "We expect with warming temperatures, the tick is going to slowly make its way northward and westward and cause more problems than they're already causing," Saff said. We've already seen that occur with the deer ticks that cause Lyme disease, and 2017 is projected to be an especially bad year.

There’s so much we don’t understand about alpha-gal sensitivity. Scientists don’t know why it happens, how to treat it, or if it's permanent. All they can do is advise us to be vigilant and follow basic tick-avoidance practices.

[h/t Business Insider]