Have you ever had a nasty infection that just won’t seem to go away? Or a runny nose that keeps coming back? You may have been dealing with a bacterium that is tolerant of, though not yet resistant to, antibiotics.

Antibiotic resistance is a huge problem, contributing to nearly 1.27 million deaths worldwide in 2019. But antibiotic tolerance is a covert threat that researchers have only recently begun to explore.

Antibiotic tolerance happens when a bacterium manages to survive for a long time after being exposed to an antibiotic. While antibiotic-resistant bacteria flourish even in the presence of an antibiotic, tolerant bacteria often exist in a dormant state, neither growing nor dying but putting up with the antibiotic until they can “reawaken” once the stress is gone. Tolerance has been linked to the spread of antibiotic resistance.

I am a microbiologist who studies antibiotic tolerance, and I seek to uncover what triggers tolerant bacteria to enter a protective dormant slumber. By understanding why bacteria have the ability to become tolerant, researchers hope to develop ways to avoid the spread of this ability. The exact mechanism that sets tolerance apart from resistance has been unclear. But one possible answer may reside in a process that has been overlooked for decades: how bacteria create their energy.

Cholera and antibiotic tolerance

Many antibiotics are designed to break through the bacteria’s outer defenses like a cannonball through a stone fortress. Resistant bacteria are immune to the cannonball because they can either destroy it before it damages their outer wall or change their own walls to be able to withstand the impact.

Tolerant bacteria can remove their wall entirely and avoid damage altogether. No wall, no target for the cannonball to smash. If the threat goes away before too long, the bacterium can rebuild its wall to protect it from other environmental dangers and resume normal functions. However, it is still unknown how bacteria know the antibiotic threat is gone, and what exactly triggers their reawakening.

My colleagues and I at the Dörr Lab at Cornell University are trying to understand processes of activation and reawakening in the tolerant bacteria responsible for cholera, Vibrio cholerae. Vibrio is rapidly evolving resistance against various types of antibiotics, and doctors are concerned. As of 2010, Vibrio is already resistant to 36 different antibiotics, and this number is expected to continue rising.

To study how Vibrio develops resistance, we chose a strain that is tolerant to a class of antibiotics called beta-lactams. Beta-lactams are the cannonball sent to destroy the bacteria’s fortress, and Vibrio adapts by activating two genes that temporarily remove its cell wall. I witnessed this phenomenon using a microscope. After removing its cell wall, the bacteria activate even more genes that morph it into fragile globs that can survive the effects of the antibiotic. Once the antibiotic is removed or degraded, Vibrio returns to its normal rod shape and continues to grow.

Normally rod-shaped Vibrio cholerae remove their cell walls and turn into globs in the presence of penicillin, enabling them to survive longer.
Vibrio cholerae revert back to their rod-shaped structure once the antibiotic threat is removed.

In people, this process of tolerance is seen when a doctor prescribes an antibiotic, typically doxycycline, to a patient infected with cholera. The antibiotic temporarily seems to stop the infection. But then the symptoms start back up again because the antibiotics never fully cleared the bacteria in the first place.

The ability to revert back to normal and grow after the antibiotic is gone is the key to tolerant survival. Exposing Vibrio to an antibiotic for a long enough time would eventually kill it. But a standard course of antibiotics often isn’t long enough to get rid of all the bacteria even in their fragile state.

However, taking a medicine for a prolonged period can harm healthy bacteria and cells, causing further discomfort and illness. Additionally, misuse and extended exposure to antibiotics can increase the chances of other bacteria residing in the body becoming resistant.

Other bacteria developing tolerance

Vibrio isn’t the only species to exhibit tolerance. In fact, researchers have recently identified many infectious bacteria that have developed tolerance. A bacteria family called Enterobacteriaceae, which include major food-borne disease pathogens Salmonella, Shigella and E. coli, are just a few of the many types of bacteria that are capable of antibiotic tolerance.

As every bacterium is unique, the way one develops tolerance seems to be as well. Some bacteria, like Vibrio, erase their cell walls. Others can alter their energy sources, increase their ability to move or simply pump out the antibiotic.

I recently found that a bacterium’s metabolism, or the way it breaks down “food” to make energy, may play a significant role in its ability to become tolerant. Different structures within a bacterium, including its outer wall, are made of specific building blocks like proteins. Stopping the bacterium’s ability to craft these pieces weakens its wall, making it more likely to take damage from the outside environment before it can take the wall down.

Tolerance and resistance are connected

Although there has been considerable research on how bacteria develop tolerance, a key piece of the puzzle that has been neglected is how tolerance leads to resistance.

In 2016, researchers discovered how to make bacteria tolerant in the laboratory. After repeated exposure to different antibiotics, E. coli cells were able to adapt and survive. DNA, the genetic material containing instructions for cell function, is a fragile molecule. When DNA is damaged rapidly by stress, such as antibiotic exposure, the cell’s repair mechanisms tend to mess up and cause mutations that can create resistance and tolerance. Because E. coli is similar to many different types of bacteria, these researchers’ findings revealed that, ironically, essentially any bacteria can develop tolerance if pushed to their limits by the antibiotics meant to kill them.

Bacteria form large communities in biofilms.

Another recent key discovery was that the longer bacteria remain tolerant, the more likely they are to develop mutations leading to resistance. Tolerance allows bacteria to develop a resistance mutation that reduces their chances of being killed during antibiotic treatment. This is especially relevant to bacterial communities often seen in biofilms that tend to coat high-touch surfaces in hospitals. Biofilms are slimy layers of bacteria that ooze a protective jelly that makes antibiotic treatment difficult and DNA sharing between microbes easy. They can induce bacteria to evolve resistance. These conditions are thought to mimic what could be happening during antibiotic-treated infections, in which many bacteria are living next to one another and sharing DNA.

Researchers are calling for more research into antibiotic tolerance with the hope that it will lead to more robust treatments in both infectious diseases and cancers. And there is reason to be hopeful. In one promising development, a mouse study found that decreasing tolerance also reduced resistance.

Meanwhile, there are steps everyone can take to aid in the battle against antibiotic tolerance and resistance. You can do this by taking an antibiotic exactly as prescribed by a doctor and finishing the entire bottle. Brief, inconsistent exposure to a medicine primes bacteria to become tolerant and eventually resistant. Smarter use of antibiotics by everyone can stop the evolution of tolerant bacteria.

Megan Keller, Ph.D. Candidate in Microbiology, Cornell University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

It’s coming. Winds are weakening along the equatorial Pacific Ocean. Heat is building beneath the ocean surface. By July, most forecast models agree that the climate system’s biggest player – El Niño – will return for the first time in nearly four years.

El Niño is one side of the climatic coin called the El Niño-Southern Oscillation, or ENSO. It’s the heads to La Niña’s tails.

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The Justice Department on April 14, 2023, charged Jack Teixeira, a 21-year-old Massachusetts Air National Guard member, with unauthorized retention and transmission of national defense information and unauthorized removal and retention of classified documents or material. Media reports suggest that Teixeira didn’t intend to leak the documents widely but rather shared them on a closed Discord community focused on playing war games.

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When we asked GPT-3, an extremely powerful and popular artificial intelligence language system, whether you’d be more likely to use a paper map or a stone to fan life into coals for a barbecue, it preferred the stone.

To smooth your wrinkled skirt, would you grab a warm thermos or a hairpin? GPT-3 suggested the hairpin.

And if you need to cover your hair for work in a fast-food restaurant, which would work better, a paper sandwich wrapper or a hamburger bun? GPT-3 went for the bun.

Why does GPT-3 make those choices when most people choose the alternative? Because GPT-3 does not understand language the way humans do.

Bodiless words

One of us is a psychology researcher who over 20 years ago presented a series of scenarios like those above to test the understanding of a computer model of language from that time. The model did not accurately choose between using rocks and maps to fan coals, whereas humans did so easily.

The other of us is a doctoral student in cognitive science who was part of a team of researchers that more recently used the same scenarios to test GPT-3. Although GPT-3 did better than the older model, it was significantly worse than humans. It got the three scenarios mentioned above completely wrong.

GPT-3, the engine that powered the initial release of ChatGPT, learns about language by noting, from a trillion instances, which words tend to follow which other words. The strong statistical regularities in language sequences allow GPT-3 to learn a lot about language. And that sequential knowledge often allows ChatGPT to produce reasonable sentences, essays, poems and computer code.

Although GPT-3 is extremely good at learning the rules of what follows what in human language, it doesn’t have the foggiest idea what any of those words mean to a human being. And how could it?

Humans are biological entities that evolved with bodies that need to operate in the physical and social worlds to get things done. Language is a tool that helps people do that. GPT-3 is an artificial software system that predicts the next word. It does not need to get anything done with those predictions in the real world.

I am, therefore I understand

The meaning of a word or sentence is intimately related to the human body: people’s abilities to act, to perceive and to have emotions. Human cognition is empowered by being embodied. People’s understanding of a term like “paper sandwich wrapper,” for example, includes the wrapper’s appearance, its feel, its weight, and, consequently, how we can use it: for wrapping a sandwich. People’s understanding also includes how someone can use it for myriad other opportunities it affords, such as scrunching it into a ball for a game of hoops, or covering one’s hair.

All of these uses arise because of the nature of human bodies and needs: People have hands that can fold paper, a head of hair that is about the same size as a sandwich wrapper, and a need to be employed and thus follow rules like covering hair. That is, people understand how to make use of stuff in ways that are not captured in language-use statistics.

Your body shapes your mind.

GPT-3, its successor, GPT-4, and its cousins Bard, Chinchilla and LLaMA do not have bodies, and so they cannot determine, on their own, which objects are foldable, or the many other properties that the psychologist J.J. Gibson called affordances. Given people’s hands and arms, paper maps afford fanning a flame, and a thermos affords rolling out wrinkles.

Without arms and hands, let alone the need to wear unwrinkled clothes for a job, GPT-3 cannot determine these affordances. It can only fake them if it has run across something similar in the stream of words on the internet.

Will a large-language-model AI ever understand language the way humans do? In our view, not without having a humanlike body, senses, purposes and ways of life.

Toward a sense of the world

GPT-4 was trained on images as well as text, permitting it to learn statistical relationships between words and pixels. While we can’t perform our original analysis on GPT-4 because it currently doesn’t output the probability it assigns to words, when we asked GPT-4 the three questions, it answered them correctly. This could be due to the model’s learning from previous inputs, or its increased size and visual input.

However, you can continue to construct new examples to trip it up by thinking of objects that have surprising affordances that the model likely hasn’t encountered. For example, GPT-4 says that a cup with the bottom cut off would be better for holding water than a lightbulb with the bottom cut off.

A model with access to images might be something like a child who learns about language – and the world – from the television: It’s easier than learning from the radio, but humanlike understanding will require the crucial opportunity to interact with the world.

Recent research has taken this approach, training language models to generate physics simulations, interact with physical environments and even generate robotic action plans. Embodied language understanding might still be a long way off, but these kinds of multisensory interactive projects are crucial steps on the way there.

ChatGPT is a fascinating tool that will undoubtedly be used for good – and not-so-good – purposes. But don’t be fooled into thinking that it understands the words it spews, let alone that it’s sentient.The Conversation

Arthur Glenberg, Emeritus Professor of Psychology, Arizona State University and Cameron Robert Jones, Doctoral Student in Cognitive Science, University of California, San Diego

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Arthur Glenberg, Arizona State University and Cameron Robert Jones, University of California, San DiegoThe Conversation

THORNHILL, Ontario - March 30, 2023  -- If you are looking to tighten your home security with cameras, there are a variety of camera types to choose from each device has their own list of features, add-ons, etc. Here at Smart Vision Plus, we want to go into detail and discuss few of the main camera types so you can better  figure out which security camera is best for your specific home situation.

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SAN FRANCISCO - March 30, 2023  -- Revive Adserver is an open-source, web-based advertising server software that allows website owners and advertisers to manage and serve ads on their websites. It was originally developed by OpenX, but in 2013, it was released as open-source software under the name OpenX Source, and later renamed Revive Adserver. Here are some of its features:

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HOUSTON - March 30, 2023  -- Gone are the days of struggling to come up with a catchy and memorable name for your website. With Namify's Website Name Generator, you can generate unique, brandable, and memorable website domain names in seconds.
Search engines have maintained that exact-match keywords in domain names make no significant difference to your website SEO, however, a contextual and brandable domain name makes it easier for visitors to remember and recall your website. Increasing the chance of your visitors returning over and over again. As Ann Smarty said in her article How Domain Names Impact SEO, "Choose a domain name not for SEO but for humans. Select a name that consumers will remember and associate with your company."

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Members of NASA’s OSIRIS-REx curation team practice with a mock glove box at the agency's Johnson Space Center in Houston. The curation team will be among the first to see and handle the sample OSIRIS-REx is returning from asteroid Bennu. They are also responsible for storing and distributing the sample to science team members around the world. Most of the sample will be stored for future generations. Credits: NASA Johnson/Bill Stafford

NASA's OSIRIS-REx spacecraft is cruising back to Earth with a sample it collected from the rocky surface of asteroid Bennu. When its sample capsule parachutes down into the Utah desert on Sept. 24, OSIRIS-REx will become the United States’ first-ever mission to return an asteroid sample to Earth.

After seven years in space, including a nail-biting touchdown on Bennu to gather dust and rocks, this intrepid mission is about to face one of its biggest challenges yet: deliver the asteroid sample to Earth while protecting it from heat, vibrations, and earthly contaminants.  

“Once the sample capsule touches down, our team will be racing against the clock to recover it and get it to the safety of a temporary clean room,” said Mike Moreau, deputy project manager at NASA's Goddard Space Flight Center in Greenbelt, Maryland.

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Materials for coating spaceplanes maintain comfort in outerwear, sports uniforms, jeans

NASA intended its Reusable Launch Vehicle program of the 1990s to demonstrate technologies that would enable hypersonic spaceplanes to make affordable, repeated trips into space. It was never intended to improve the performance of hunting, skiing, and sports gear, but, more than 20 years after its cancellation, that’s what’s happened.

One of the program’s most successful spinoffs has been a substance dubbed Protective Coating for Ceramic Materials, or PCCM, which NASA’s Ames Research Center in Silicon Valley, California, invented to protect the spaceplanes’ heat shields during atmospheric re-entry. NASA patented the coating, and Wessex Inc. – now known as Emisshield Inc. – licensed it and started developing commercial products.

The material isn’t a traditional insulator, and it’s not reflective. Instead, it has remarkably high emissivity, meaning it could absorb heat from a heat shield and radiate it away from the spacecraft. Emisshield has adapted PCCM into dozens of formulas now coating industrial equipment around the world (Spinoff 2001, 2004, 2011, 2019).

In 2013, Brad Poorman and Jim Hind incorporated Clean Textile Technology LLC, now of North Naples, Florida, and were looking for a niche in high-tech textiles when they learned of PCCM. They approached Emisshield, which agreed to license its technology exclusively to them for use in fabrics in exchange for a share in the brand.

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The Defense Department is using geospatial, or mapping, technology in a tool that will soon be available to assist countries and organizations dealing with the deadly consequences of hurricanes, earthquakes and other disasters and humanitarian crises, experts from DoD and U.S. Southern Command said in a recent DoD News interview.

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