Efficacy of new gene therapy approach for toxin exposures shown in mouse study

The current method to treat acute toxin poisoning is to inject antibodies, commonly produced in animals, to neutralize the toxin. But this method has challenges ranging from safety to difficulties in developing, producing and maintaining the anti-serums in large quantities.

New research led by Charles Shoemaker, Ph.D., professor in the Department of Infectious Disease and Global Health at the Cummings School of Veterinary Medicine at Tufts University, shows that gene therapy may offer significant advantages in prevention and treatment of botulism exposure over current methods. The findings of the National Institutes of Health funded study appear in the August 29 issue of PLOS ONE.

Shoemaker has been studying gene therapy as a novel way to treat diseases such as botulism, a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium Clostridium botulinum. Despite the relatively small number of botulism poisoning cases nationally, there are global concerns that the toxin can be produced easily and inexpensively for bioterrorism use. Botulism, like E. coli food poisoning and C. difficile infection, is a toxin-mediated disease, meaning it occurs from a toxin that is produced by a microbial infection.

Shoemaker's previously reported antitoxin treatments use proteins produced from the genetic material extracted from alpacas that were immunized against a toxin. Alpacas, which are members of the camelid family, produce an unusual type of antibody that is particularly useful in developing effective, inexpensive antitoxin agents. A small piece of the camelid antibody -- called a VHH -- can bind to and neutralize the botulism toxin. The research team has found that linking two or more different toxin-neutralizing VHHs results in VHH-based neutralizing agents (VNAs) that have extraordinary antitoxin potency and can be produced as a single molecule in bacteria at low cost. Additionally, VNAs have a longer shelf life than traditional antibodies so they can be better stored until needed.

The newly published PLOS ONE study assessed the long-term efficacy of the therapy and demonstrated that a single gene therapy treatment led to prolonged production of VNA in blood and protected the mice from subsequent exposures to C. botulinum toxin for up to several months. Virtually all mice pretreated with VNA gene therapy survived when exposed to a normally lethal dose of botulinum toxin administered up to nine weeks later. Approximately 40 percent survived when exposed to this toxin as late as 13 or 17 weeks post-treatment. With gene therapy the VNA genetic material is delivered to animals by a vector that induces the animals to produce their own antitoxin VNA proteins over a prolonged period of time, thus preventing illness from toxin exposures.

The second part of the study showed that mice were rapidly protected from C. botulinum toxin exposure by the same VNA gene therapy, surviving even when treated 90 minutes after the toxin exposure.

"We envision this treatment approach having a broad range of applications such as protecting military personnel from biothreat agents or protecting the public from other toxin-mediated diseases such as C. difficile and Shiga toxin-producing E. coli infections," said Shoemaker, the paper's senior author. "More research is being conducted with VNA gene therapy and it's hard to deny the potential of this rapid-acting and long-lasting therapy in treating these and several other important illnesses."

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The above story is based on materials provided by Tufts University . Note: Materials may be edited for content and length.

Two Common Misconceptions About Learning

It’s another semester with a new group of students. This semester, I have a class of elementary education majors (using Physics and Everyday Thinking). In the course, students build basic physics ideas after collecting data from particular experiments. Overall, this is an awesome course. It seems that most of the students gain a greater understanding of the nature of science by the end of the course.

However, things don’t always start off with rainbows and unicorns. Many of the students come in with 2 big ideas that don’t really agree with the nature of learning. Oh, and it’s not just this course – I see the same thing other physics courses.

Common Student Idea 1: Confusion is Bad.

If I come into a class and I become confused, then something is wrong. It’s probably something wrong with me – maybe I’m stupid. It’s also possible that this is the instructor’s fault for not being clear enough.

I’ve written about this before, and it comes down to one line: Confusion is the sweat of learning. If a student doesn’t get confused at some point in a class then either the student already knew the material in class, or the student didn’t learn anything in class. It’s just like going to a gym to work out. If you didn’t sweat and you didn’t get sore afterwards, you probably didn’t do anything.

I hate to put the blame on others, but I don’t think this incorrect idea is the students’ fault. No, it is our fault (our collect fault as educators). Think of all the classes that portray confusion as the enemy of understanding. Actually, I just came up with another quote: confusion isn’t the enemy of understanding, they are allies.

In short, I think that classes that foster confusion should be the norm, not the exception. It’s clear that when students come into my physics class, confusion is not what they expect as a positive outcome.

Common Student Idea 2: The Instructor is the Source of Knowledge.

If you traced back the source of understanding, it would be like a river flowing from the mouth of the professor. This isn’t so crazy. The word professor comes from the word profess – to claim something. So, a professor proclaims the truth and students write it down. It’s that simple. Oh, the textbook is just like a professor. If it’s written in a textbook, it must be the truth.

The problem here is that students think that if I don’t tell them the answers, they can’t know the answers. If I don’t tell them the answers, I am holding back on the sharing of knowledge. This might be true for some cases. It is true for lower level understanding such as the names of different animals or body parts. It is sort of true for the dates of historical events (but not entirely true) and it could be true for other definitions. However, this is not true for most things in physics. Let me give an example.

What happens when there is a constant net force on an object? Does the student just have to take the word of the professor that the object’s velocity will change with a constant force? Absolutely not. There are countless experiments that a student could perform to determine this same idea (if you want a quick one, try this awesome simulator from PhET).

But wait! What if we (students) build an idea from evidence and it’s wrong? What if this is a test question and we get it wrong? The professor is clearly the authority of knowledge when it comes to grading a test. Well, that is a good point. But really, this goes to show that an instructor actually has two different jobs. Job one is to be a learning coach and assist in the learning process. Job two is to be an evaluator of understanding. Personally, I don’t mind evaluating students to help them improve their understanding but the whole grading thing can get in the way of learning.

What should we do to help students with these learning misconceptions? I think the best plan is to make sure that all of the classes (or at least most) include an element of confusion along with a dose knowledge building. Let’s not have anymore flash-card based courses.

Lunch Carriers That’ll Keep Your Soups Steamy and Your Food Partitioned

Lunchbox wizardry used to mean packing your juice pouch to keep your apple from smooshing your PB&J. Today’s carriers are built for more discerning appetites. Bon appétit! Jarren Vink

Best for: OCD epicures looking for order in the transport of their three-course meals.

Even if lunch is last night's unwieldy takeout, the Bentgo will provide suitable accommodations. A full set of plastic utensils—fork, knife, and spoon—snaps into the divider lid, and the top tray is partitioned to keep your veggies from infiltrating your dessert. Just don't pack anything too juicy: The lids keep your bag safe from your green beans, but soup will seep out.

Best for: Eaters who like their calories hot and are cool with slurping in public.

A spoonful of soup can do miracles for midday stress, and the vacuum-insulated, double-walled King will keep your goulash hot for up to seven hours. The design is compact and complete, with a built-in spoon and a lid that doubles as a bowl. Cleaning the widemouthed Thermos is easy, but make sure soup crust doesn't build up in the spoon's articulated joints.

Defuse a Bomb With Friends In This Brilliant Oculus Game

PAX attendees play Keep Talking and Nobody Explodes on Saturday. Chris Kohler/WIRED

SEATTLE — It’s a typical action-movie cliche. Someone has to disarm a bomb, but they know nothing about how to do it. Fortunately, they have a bomb-defusal expert—on the phone. Hijinks ensue as the expert tries to talk the newbie through the delicate process.

Admit it, you’ve always wanted to do this in real life. This new Oculus game gives you that chance.

On the show floor at Penny Arcade Expo, currently taking place in Seattle through Monday evening, a small table with easily-missable signage hosts the demo version of Keep Talking and Nobody Explodes , currently in development for the Oculus Rift virtual reality headset. It’s so early in development that the team, three guys who met in the Ottawa game development scene, doesn’t even have a name yet. But they’ve got a corker of a proof-of-concept. It’s easily the most exciting new idea I found at PAX.

Keep Talking got its start when Ottawa area indie developers Allen Pestaluky, Ben Kane and Brian Fetter worked together on a Global Game Jam project in January of this year. The idea came from an episode of the animated show Archer that had a bomb-disarming bit, Pestaluky says. “They were trying to communicate back and forth, and all of these silly things came up when they were talking, trying to defuse the bomb.”

Within a week, a YouTube video of their Game Jam version, created over a single weekend, had racked up over 150,000 views, Pestaluky said. Since then, they’ve been working on the game full-time, and plan to release it on the day that the consumer version of the Oculus becomes available—whenever that is.

Screenshot of Keep Talking and Nobody Explodes Keep Talking Team

Keep Talking consists of two separate but inextricable pieces: the Oculus Rift software, and a paper manual sitting on the demo table in a three-hole notebook. The bomb that players see on screen is composed of any number of different modules, each of which is a miniature puzzle: a series of colored wires, an array of lights, or maybe just a big red button that reads “PRESS.”

Each page of the manual relates to a different module. Only you don’t know which ones are on the bomb. So the player disarming the bomb first starts describing what the modules look like. The twist, which immediately becomes apparent, is that the player isn’t sure what information is useful and what is noise: Do you need to know the color of the wires? The orientation? The length? This is figured out by the reader of the manual, a dense wall of text that explains how to solve each puzzle.

The manual text is, deliberately, a bit scattershot and overwrought. “We’ve had a lot of interesting challenges regarding, how do you structure the rules in the manual so that they’re fair, but also challenging and interesting?” says Pestaluky. “As we’ve played with players, we’ve been feeling out how people are able to understand text. Kids are interesting. Kids will read line by line much better than adults, who kind of learn to skip.”

Once the reader wades through the blocks of text and figures out what action to take, they can tell the bomb-defuser to cut the correct wire, or press the button, or not press the button. Assuming they don’t explode, they can move on to the next module.

First-time players of the demo can choose a mode in which they have five minutes to disarm three modules, which are always the first three modules in the book. “Normal” mode uses half the book, roughly 10 pages. “Expert” mode uses the whole thing. The game will be distributed with a digital manual that can be printed or just viewed on a tablet or laptop.

If you want to step up the difficulty, you can customize the time limit and number of modules. “You can easily make it so that it’s not humanly possible,” Pestaluky says.

Keep Talking creates a wonderfully asymmetric challenge. The defusal expert can’t cheat and peek at the screen, and the player in the Rift can’t steal a glance at the manual either. From either side of the scenario, it’s a hell of a lot of fun to have to rely on only the words of the person next to you, with whom you can’t even make eye contact.

Playing the game tends to create an atmosphere that Pestaluky describes as “silly tense”: Nerve-wracking, but the sort of thing you can laugh about immediately following. But that’s not to say Keep Talking might not be responsible for a few fights.

“We’ve seen some married couples, and couples who [place] a strong importance on their communication skills,” says Pestaluky. “When they see their communication break down, it can sometimes invoke a whole bunch of negative emotions, which is kind of funny.”

An Interactive Ceiling That Undulates as You Pass Under

Gif: WIRED

“In Norway it’s kind of hard not to be involved in the oil economy,” says Bjørn Gunnar Staal, a lead designer at Scandinavian Design Group. When drillers discovered an abundance of oil on the Norwegian continental shelf in 1969, it sparked an economic boom that’s lasted well into this century. Over the years the government has re-invested wealth from petroleum back into the energy sector, into a massive welfare program, and, notably, into subsidies for young architects and designers. That’s now coming full circle, as Scandinavian Design Group, one of Norway’s oldest graphic design studios, has just created an interactive installation for Norway’s branch of Lundin Petroleum, Sweden’s largest oil company.

The installation went live at a Scandinavian energy conference. But when Lundin asked Scandinavian Design Group for a proposal for their booth, Staal proposed something that actually isn’t a booth at all: An undulating ceiling of honey-colored tubes that would rhythmically move in response to the visitors walking underneath. They’re calling it Breaking the Surface.

This Selfie-Friendly Camera Is Good for Non-Egomaniacal Photography, Too

Olympus

Olympus’s mirrorless camera lineup runs the gamut from larger-sized DSLR replacements like the flagship OM-D E-M1 to pint-size, beginner-friendly cameras like the PEN E-PL7, which was just announced. The company is positioning it as a step-up camera for smartphone photographers, and true to that billing, it has a 180-degree flip-down touchscreen for framing and shooting selfies.

Of course, you don’t have to use this camera to take selfies, but the tilting 3-inch touchscreen is a unique twist on an existing design. In “selfie mode,” which is automatically enabled when the LCD screen is tipped all the way down to face forward, you get a pared-down UI that lets you tap the screen to focus and shoot quickly. By flipping downward instead of upward, the hotshoe and control dials don’t obscure the lower portion of the screen, and it’ll let you frame duck-face shots from more-flattering angles.

Like many of Olympus’s recent cameras, the E-PL7 also has built-in Wi-Fi to share photos of your own face more quickly. The sidecar Olympus Image Share app for iOS and Android also lets you remotely control the camera from a smartphone, and the options are pretty extensive: Manual exposure controls, a remote live view, and zoom capabilities when you’re using a powered zoom lens with the camera.

Otherwise, the camera shares features with the E-PL5, including a 16-megapixel Micro Four-Thirds sensor, ISO settings up to 25,600, 12-bit RAW and RAW+JPG shooting, and a body-based 3-axis stabilization system. While the new camera’s continuous-shooting speed remains a brisk 8fps without AF enabled, the autofocus system has been beefed up quite a bit. The E-PL7 has an 81-point contrast-detection system that offers more coverage than the 35-point system of the E-PL5.

The PEN series’ more-compact size means you won’t get all the knobs and buttons of the O-MD lineup, but it still has manual and semi-manual exposure controls. Fans of Olympus’s in-camera Art filters (which are awesome) should be excited about the addition of a selective-color mode that lets you highlight one color in an otherwise black-and-white photo.

Price-wise, it’s also inspired by the E-PL5. The new PEN E-PL7 will cost $600 for the body in black or silver, or $700 as a kit with a (non-powered) 14-42mm zoom lens. It’s available for preorder now and will be shipping in September.

Out in the Open: Hackers Build a Skype That’s Not Controlled by Microsoft

Screenshot: WIRED/Source: Tox

The web forum 4chan is known mostly as a place to share juvenile and, to put it mildly, politically incorrect images. But it’s also the birthplace of one of the latest attempts to subvert the NSA’s mass surveillance program.

When whistleblower Edward Snowden revealed that full extent of the NSA’s activities last year, members of the site’s tech forum started talking about the need for a more secure alternative to Skype. Soon, they’d opened a chat room to discuss the project and created an account on the code hosting and collaboration site GitHub and began uploading code.

Eventually, they settled on the name Tox, and you can already download prototypes of the surprisingly easy-to-use tool. The tool is part of a widespread effort to create secure online communication tools that are controlled not only by any one company, but by the world at large—a continued reaction to the Snowden revelations. This includes everything from instant messaging tools to email services.

It’s too early to count on Tox to protect you from eavesdroppers and spies. Like so many other new tools, it’s still in the early stages of development and has yet to receive the scrutiny that other security tools, such as the instant messaging encryption plugin Off The Record has. But it endeavors to carve a unique niche within the secure communications ecosystem.

‘Up to Your Imagination’

The main thing the Tox team is trying to do, besides provide encryption, is create a tool that requires no central servers whatsoever—not even ones that you would host yourself. It relies on the same technology that BitTorrent uses to provide direct connections between users, so there’s no central hub to snoop on or take down.

There are other developers trying to build a secure, peer-to-peer messaging systems, including Briar and Invisible.im, a project co-created by HD Moore, the creator of the popular security testing framework Metasploit. And there are other secure-centric voice calling apps, including those from Whisper Systems and Silent Circle, which encrypt calls made through the traditional telco infrastructure. But Tox is trying to roll both peer-to-peer and voice calling into one.

Actually, it’s going a bit further than that. Tox is actually just a protocol for encrypted peer-to-peer data transmission. “Tox is just a tunnel to another node that’s encrypted and secure,” says David Lohle, a spokesperson for the project. “What you want to send over that pipe is up to your imagination.” For example, one developer is building an e-mail replacement with the protocol, and Lohle says someone else is building an open source alternative to BitTorrent Sync.

The New Skype

That said, the core Tox team is focused on building the features specifically required for building a Skype replacement. There are at least 10 different Tox messaging and voice clients so far, each supporting a different range of features. Eventually, Lohle says, there will be “official” clients for each major operating system, but for now the team is just recommending a few specific clients. µTox, which is available for Linux and Windows, is a the “bleeding edge” reference design, while qTox is the project’s recommendation for OS X users and Antox is the recommended for Android. There is no iOS version as of yet.

µTox is still rough, but the interface and experience is straightforward. You download the client, and it automatically creates a public encryption key that you can provide to everyone, and a private encryption key that you keep on your computer or phone. From there, it works very much like Skype. You can add a friend to your contact list by pasting in their public key, and then you just click their name to send them a message, or click the big phone icon to call them. If you want to move your identity from one computer to another, you just copy a single file that includes your private key and contact list.

There are still a few features that are missing, though. For example, there’s no way to do a group chat yet. And there’s no way to be logged in as the same person on two different devices — say, both your phone and your computer. But Lohle says those features are coming, and the team already as a proof-of-concept for how group chat will work.

He says the team has no plans to turn it into a company or monetize it in any way. “No one getting paid, but we dedicate as much time as we can,” he says. “If I’m not in class, or I’m not eating, I’m probably working on Tox, and that’s at least the same for probably 10 people.” Besides, the lead developer, known only as irungentoo, is completely anonymous, so it would be hard to issue him a paycheck. “I don’t think any of us know his real name,” Lohle says.

The Link With 4Chan

Today Lohle downplays Tox’s relationship to 4chan. “We were self-sufficient after only a couple weeks,” he says. “We also posted on reddit and hacker news, and people joined from that.” He probably has good reason to distance the project from the site. The racism, homophobia and misogyny on display on the 4chan on a day to day basis would be a big turn off both for users and potential contributors.

The association has also exposed the project to the trolling and drama characteristic of the forum, which often makes it hard for outsiders to evaluate. For example, one Tox developer raised concerns about Tox users exposing their IP addresses to each other. The team responded by masking IP addresses through a technology called onion routing — the same technique that the Tor Project uses to protect user anonymity on the web. But the fix didn’t stop a wave of paranoia from sweeping forums, and it’s hard to tell how much of that is trolling and how much of it is legitimate concern.

Can You Trust It?

Worse, the project let its “warrant canary” page go offline for a week. A warrant canary is usually a website that states that a company or organization has not be served by a secret subpoena from the NSA or any other law enforcement or intelligence agency. It’s meant as a way to bypass laws that prevent companies from warning their customers that they have been served with a national security letter. The Tox team claimed in a blog post that they simply forgot to put the warrant canary back online after moving web hosts. But the incident led to degree of understandable suspicion.

Meanwhile, few security experts outside the project have reviewed the Tox code yet, but the project is based on an existing set of code libraries for working with crypto algorithms called NaCl, which has received considerably more attention. “NaCl is a newish library that is nevertheless very highly regarded in the security community, produced by skilled people,” says the Electronic Freedom Frontier senior staff technologist Jacob Hoffman-Andrews, who hasn’t yet evaluated Tox.

But it’s entirely possible to good crypto libraries in poor ways, so the Tox team is saving money to hire a professional security firm to audit the code once it reaches a more stable state. “Right now we’re relying on the open source community,” Lohle says. “We have about 15 who stare at the code for days or weeks.”