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Drilling down on treatment-resistant fungi with molecular machines

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Drilling down on treatment-resistant fungi with molecular machines

Newly developed molecular drills may be able to fight treatment-resistant fungal infections like Candida auris.
Dr_Microbe/iStock via Getty Images

Ana L. Santos, Rice University; Jacob Beckham, Rice University, and James Tour, Rice University

Fungi are present on the skin of around 70% of the population, without causing harm or benefit. Some fungal infections, like athlete's foot, are minor. Others, like Candida albicans, can be deadly – especially for individuals with weakened immune systems.

Fungal infections are on the rise because of an aging population and an increased prevalence of chronic diseases. At the same time, fungi are becoming more resistant to treatment. As a result, fungal infections could soon become a serious public threat.

In 2022, the World Health Organization released its first-ever “Fungal Priority Pathogen List,” calling for improved surveillance, public health interventions and the of new antifungal .

We are an interdisciplinary team of chemists and biologists charting a new path to tackle drug-resistant infections. We are using tiny nanoscale drills that combat harmful pathogens at the molecular level. As the traditional antimicrobial research pipeline struggles, our approach has the potential to rejuvenate the fight against these stubborn infections.

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Molecular machines as alternative antifungals

While doctors urgently need new antifungal drugs, developing them is challenging. First, it is difficult to develop drugs that selectively kill fungi without harming human cells because of their many similarities.

Second, fungi can rapidly develop resistance to multiple antifungal drugs at once when medications are misused or overused. As such, developing antifungal drugs is much less rewarding for drug companies than developing medications for chronic conditions like diabetes and hypertension that require long-term use.

One solution to this problem could lie in a Nobel Prize-winning technology: molecular machines.

Molecular machines are synthetic compounds that rapidly rotate their components at about 3 million times per second when exposed to light. Doctors can use a light-tipped probe to activate these molecular machines to treat internal infections, or a lamp for skin infections. The light starts the machines spinning, and that rotational motion pushes them to drill through and puncture the cell's membranes and organelles, which results in cell death.

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Our group first used this technology to kill cancer cells in 2017. To target the right cells, molecular machines can be linked to specific peptides that bind only to the desired cells, allowing, for instance, the targeting of specific cancer types. Since then, we have used these molecules to kill bacteria, destroy tissue and stimulate muscle contraction. These properties make molecular machines an enticing candidate technology to address the growing fungal threat.

A diagram showing the structure of a molecular machine as gray lines connected in the shape of several hexagons
The 3D structure of a molecular machine. The molecular machine consists of rotor (top) and stator (bottom) portions connected by a central axle. Following light activation, molecular machines rotate rapidly, drilling into fungal cells.
Tour Lab, Rice

Testing antifungal molecular machines

Researchers first tested the ability of light-activated molecular machines to kill fungi in Candida albicans. This yeastlike fungus can cause life-threatening infections in immunocompromised people. Compared with conventional drugs, molecular machines killed C. albicans much faster.

Subsequent studies found that molecular machines could also kill other fungi, molds like Aspergillus fumigatus and species of dermatophytes, the types of fungi that cause skin, scalp and nail infections. Molecular machines even eliminated fungal biofilms, which are slimy, antimicrobial-resistant communities of microorganisms that stick together on surfaces and commonly cause medical device-associated infections.

Unlike conventional antifungals, which target the fungal cell membrane or cell wall, molecular machines localize to the fungal mitochondria. Often referred to as the “powerhouses of the cell,” mitochondria produce energy to power other cellular activities. When activated with visible light, molecular machines destroy the fungal mitochondria. Once the fungal cell's mitochondria stop working, the cell loses its energy supply and dies.

Two black-and-white electron microscopy images of a fungal cell. The left image shows a large, round, healthy cell, while the cell on the right is shrunken following treatment with light-activated molecular machines.
Candida albicans before and after being exposed to light-activated molecular machines. Molecular machines puncture C. albicans‘ cell wall and intracellular organelles, eventually killing the fungal cell.
Matthew Meyer/Rice University.

At the same time, molecular machines also disrupt the tiny pumps that antifungal agents from the cell, thus preventing the cell from fighting back. Because these molecular machines act by a mechanical instead of a chemical mechanism, fungi are unlikely to develop defenses against this treatment.

In lab experiments, combining light-activated molecular machines with conventional antifungal drugs also reduced the amount of fungi in C. albicans-infected worms and in pig nails infected with Trichophyton rubrum, the most common cause of athlete's foot.

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New frontiers for fighting fungal infections

These results suggest that combining molecular machines with conventional antifungals can improve existing therapies and new options for treating resistant fungal strains. This strategy could also reduce the side effects of traditional antifungals, such as gastrointestinal upset and skin reactions.

Fungal infection rates will likely continue to rise. As such, the need for new treatments will only become more urgent. Climate change is already causing new human pathogenic fungi to emerge and spread, including Candida auris. C. auris is often resistant to treatment and spread rapidly in facilities during the COVID-19 pandemic. According to the Centers for Disease Control and Prevention, strained health care , overuse of immunosuppressants and misuse of antibiotics have all been implicated in outbreaks of C. auris.

In the future, researchers could use artificial intelligence to create better antifungal molecular machines. By using AI to predict how different molecular machines will interact with fungi and human cells, we can develop safer and more effective antifungal molecules that specifically kill fungi without harming healthy cells.

Antifungal molecular machines are still in the early stages of development and are not yet available for routine clinical use. However, continuing research gives hope that these machines could one day provide better treatments for fungal infections and other infectious diseases.The Conversation

Ana L. Santos, Postdoctoral Fellow in Microbiology, Rice University; Jacob Beckham, Graduate Student in Chemistry, Rice University, and James Tour, Professor of Chemistry, Rice University

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

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For millions of Americans, high-speed internet is unavailable or unaffordable − a telecommunications expert explains how to bring broadband to the places that need it the most

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theconversation.com – Christopher Ali, Pioneers Chair in Telecommunications & Professor of Telecommunications, Penn State – 2024-04-24 07:37:58

Broadband is noticeably missing in rural, remote or Indigenous areas.

Grant Faint/The Image Bank via Getty Images

Christopher Ali, Penn State

Millions of Americans still don't have access to high-speed internet. Christopher Ali, a professor of telecommunications at Penn State , discusses who lacks access to broadband and how the federal government – with a US$65 billion commitment – is trying to bring more people online.

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Christopher Ali discusses the challenges in bringing high-speed internet to underserved America.

has collaborated with SciLine to bring you highlights from the discussion that have been edited for brevity and clarity.

What is broadband internet?

Christopher Ali: Broadband internet, often just called broadband, is the technical term for high-speed internet connectivity.

The Federal Communications Commission, which is in charge of setting an official definition for broadband in the country, defines broadband as an always-on internet connection of 100 megabits-per-second download and 20 megabits-per-second upload.

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But what high-speed internet fundamentally means to Americans is do we have the connectivity necessary to go about our digital lives. Can we stream Netflix? Can we go on Zoom? Can we file our taxes? Can we do our homework? Can we do our jobs? Can we ?

What can you tell us about disparities in broadband access?

Christopher Ali: One of the really frustrating things is, despite millions – tens of millions – of dollars spent on broadband mapping, we are still unsure of who is underconnected throughout the country.

Right now, the FCC reports that 7.2 million people lack access, but the commission numbers have been historically . As a result, there are no doubt many more who are unserved and undercounted. In fact, the FCC repeatedly receives challenges to its broadband map.

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Back in 2021, for instance, when the FCC reported that about 14 million people lacked internet access, an independent review found that 42 million people lacked access. That's a huge discrepancy.

But one thing is certain: Broadband deserts are most often found in rural, remote and Indigenous areas.

It's also clear that cost is part of the issue. Here in the U.S., we pay a tremendous amount of money – the most for internet access monthly than almost any other country in the developed world.

A program called the Affordable Connectivity Program subsidizes broadband for low-income families, and 50 million families across the country are eligible.

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Without robust broadband access, communities risk being sidelined in the 21st century economy.

What benefits does broadband access ?

Christopher Ali: Broadband access can aid with economic development. It can be a game changer when it to telehealth, especially for rural, remote and Indigenous communities, which often don't have enough doctors and nurses. With telehealth, you can suddenly connect with a professional.

It aids in education. Some studies have found that access to broadband can impact grades and SAT scores, although there is disagreement about this. But the opportunities for students with broadband are undeniable – like applying online for college and student aid.

It contributes to civic engagement, allowing voters to contact local officials online. It impacts public safety, both in terms of our own safety as members of the public but also by allowing first responders to communicate online with their dispatch.

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Broadband also helps sometimes with cultural enrichment, and we see this a lot with Indigenous communities, which can stream cultural and traditional .

And it improves quality of life. Everyone enjoys being able to FaceTime with family and friends and go shopping online. These things were particularly essential during the COVID-19 pandemic.

The Broadband Equity, Access, and Deployment Program, passed as part of the 2023 bill, allocates $42 billion in federal funds to expand broadband infrastructure. How can communities maximize its impact?

Christopher Ali: The money from the BEAD program is going to be managed by the states and not by the federal government. Each state receives a chunk of money, depending on the number of people who are unconnected. Texas, with more than 1 million unserved or underserved locations, will get $3.3 billion, the most of any state. Pennsylvania will get about $1.2 billion.

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What states have done a particularly good job expanding broadband access?

Christopher Ali: Minnesota has done some amazing work over the past decade. As I discuss in my book “Farm Fresh Broadband: The Politics of Rural Connectivity,” Minnesota was one of the earliest states to create a broadband grant program – the Border-to-Border program – and has set really ambitious targets. Back in 2016, for instance, the state set up a goal of universal coverage at 100Mbps/20Mbps by 2026.

Another state is Virginia, which really got a wake-up call during the pandemic, and it mobilized a lot of the federal money that came down the pipes to empower counties, cooperatives and local ISPs.

Vermont has done something called communication union districts. They've communities to come together to use public funding to deploy broadband networks.

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Public networks are going to be a game changer because they empower communities to connect themselves and direct their own digital futures – either with municipally funded networks, or cooperatives, or some sort of public-private partnerships.

Watch the full interview to hear more.

SciLine is a free service based at the American Association for the Advancement of Science, a nonprofit that helps journalists include scientific evidence and experts in their news stories.The Conversation

Christopher Ali, Pioneers Chair in Telecommunications & Professor of Telecommunications, Penn State

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

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What is ‘techno-optimism’? 2 technology scholars explain the ideology that says technology is the answer to every problem

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theconversation.com – Seyram Avle, Associate Professor of Global Digital , UMass Amherst – 2024-04-24 07:38:14

When venture capitalist and techno-optimist Marc Andreessen speaks, many people listen.

Steve Jennings/Getty Images for TechCrunch

Seyram Avle, UMass Amherst and Jean Hardy, Michigan State University

Silicon Valley venture capitalist Marc Andreessen penned a 5,000-word manifesto in 2023 that gave a full-throated call for unrestricted technological progress to boost markets, broaden energy production, improve education and strengthen liberal democracy.

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The billionaire, who made his fortune by co-founding Netscape – a 1990s-era company that made a pioneering web browser – espouses a concept known as “techno-optimism.” In summing it up, Andreessen writes, “We believe that there is no material problem – whether created by nature or by technology – that cannot be solved with more technology.”

The term techno-optimism isn't new; it began to appear after World War II. Nor is it in a of decline, as Andreessen and other techno-optimists such as Elon Musk would have you believe. And yet Andreessen's essay made a big splash.

As scholars who study technology and society, we have observed that techno-optimism easily attaches itself to the public's desire for a better future. The questions of how that future will be built, what that future will look like and who will benefit from those changes are harder to answer.

Why techno-optimism matters

Techno-optimism is a blunt tool. It suggests that technological progress can solve every problem known to humans – a belief also known as techno-solutionism.

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Its adherents object to commonsense guardrails or precautions, such as limiting the number of new Uber drivers to ease traffic congestion or protect cab drivers' livelihoods. They dismiss such regulations or restrictions as the concerns of Luddites – people who resist disruptive innovations.

In our view, some champions of techno-optimism, such as Bill Gates, rely on the of philanthropy to promote their techno-optimist causes. Others have argued that their philanthropic initiatives are essentially a public relations effort to burnish their reputations as they continue to control how technology is being used to address the world's problems.

The stakes of embracing techno-optimism are high – and not just in terms of the role that technology plays in society. There are also political, environmental and economic ramifications for holding these views. As an ideological position, it puts the interests of certain people – often those already wielding immense power and resources – over those of everyone else. Its cheerleaders can be willfully blind to the fact that most of society's problems, like technology, are made by humans.

Many scholars are keenly aware of the techno-optimism of social media that pervaded the 2010s. Back then, these technologies were breathlessly covered in the media – and promoted by investors and inventors – as an to connect the disconnected and bring information to anyone who might need it.

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Yet, while offering superficial solutions to loneliness and other social problems, social media has failed to address their root structural causes. Those may include the erosion of public spaces, the decline of journalism and enduring digital divides.

Young boy plays with a VR headset while looking at a huge computer monitor screen with both hands outstretched.

When you play with a Meta Quest 2 all-in-one VR headset, the future may look bright. But that doesn't mean the world's problems are being solved.

Nano Calvo/VW Pics/Universal Images Group via Getty Images

Tech alone can't fix everything

Both of us have extensively researched economic development initiatives that seek to promote high-tech entrepreneurship in low-income communities in Ghana and the United States. State- programs and public-private partnerships have sought to narrow digital divides and increase access to economic opportunity.

Many of these programs embrace a techno-optimistic mindset by investing in shiny, tech-heavy fixes without addressing the inequality that led to digital divides in the first place. Techno-optimism, in other words, pervades governments and nongovernmental , just as it has influenced the thinking of billionaires like Andreessen.

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Solving intractable problems such as persistent poverty requires a combination of that sometimes, yes, includes technology. But they're complex. To us, insisting that there's a technological fix for every problem in the world seems not just optimistic, but also rather convenient if you happen to be among the richest people on Earth and in a position to profit from the technology industry.

The Bill & Melinda Gates Foundation has provided for U.S. and provides funding for The Conversation internationally.The Conversation

Seyram Avle, Associate Professor of Global Digital Media, UMass Amherst and Jean Hardy, Assistant Professor of Media & Information, Michigan State University

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

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Transporting hazardous materials across the country isn’t easy − that’s why there’s a host of regulations in place

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theconversation.com – Michael F. Gorman, Professor of Business Analytics and Operations Management, of Dayton – 2024-04-22 07:39:34
Hazardous materials regulations make sure that the vehicles carrying them have the right labels.
Miguel Perfectti/iStock via Getty Images Plus

Michael F. Gorman, University of Dayton

Ever wonder what those colorful signs with symbols and numbers on the backs of trucks mean? They're just one visible part of a web of regulations that aim to keep workers and the safe while shipping hazardous waste.

Transporting hazardous materials such as dangerous gases, poisons, harmful chemicals, corrosives and radioactive material across the country is risky. But because approximately 3 billion pounds of hazardous material needs to go from place to place in the U.S. each year, it's unavoidable.

With all the material that needs to cross the country, hazardous material spills from both truck and rail transportation are relatively unavoidable. But good regulations can keep these incidents to a minimum.

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As an operations and logistics expert, I've studied hazardous materials transportation for years. agencies from the municipal to federal levels have rules governing the handling and transportation of these materials, though they can be a little complicated.

A hazardous material is anything that can cause a or safety risk to people or the environment. Regulators put hazardous materials into nine categories and rate them based on the level of danger they pose during transport and handling.

These ratings help anyone associated with the shipment take precautions and figure out the right packaging and transportation methods for each type of hazardous material.

Who regulates hazardous material?

A number of agencies across the country closely scrutinize the entire hazardous materials supply chain from start to finish. The Occupational Safety and Health Administration regulates the proper handling of hazardous materials where they're either manufactured or used. OSHA puts limits on how much hazardous material one person can be exposed to and for how long.

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If the material spills, or if there's any left over when they're done being used, the U.S. Environmental Protection Agency, handles its disposal. Both EPA and OSHA regulations into play during spills.

In between, the U.S. Department of Transportation regulates all of the movement of hazardous materials through four of its administrations.

The Pipeline and Hazardous Materials Safety Administration regulates the transportation of hazardous materials by truck, rail, pipeline and ship. The Federal Railroad Administration plays a role in regulating rail shipments, just as the Federal Highway Administration oversees movement over the road. In the , the Federal Aviation Administration regulates hazardous materials.

Key regulations

Two essential regulations govern the handling and transportation of hazardous materials. In 1975, the EPA published the Hazardous Material Transportation Act, which protects people and property from hazardous material transportation risks.

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This act gave the secretary of transportation more regulatory and enforcement authority than before. It gave the secretary power to designate materials as hazardous, add packaging requirements and come up with operating rules.

The Pipeline and Hazardous Materials Safety Administration oversees hazardous materials regulations that apply to everything from packaging and labeling to loading and unloading procedures. They also include requirements for workers who have to handle hazardous materials and plans to make sure these materials stay secure.

Along with the Federal Highway Administration, the Pipeline and Hazardous Materials Safety Administration and the Federal Motor Carrier Safety Administration regulate hazardous material movement by road.

A white label reading
Hazardous material regulations require proper labeling of trucks carrying materials.
BanksPhotos/E+ via Getty Images

Trucking companies transporting hazardous materials need to use specific vehicles and qualified drivers to comply with Federal Motor Carrier Safety Administration regulations. Drivers transporting hazardous materials must have specialized training and a hazardous materials endorsement on their commercial driver's license.

The Pipeline and Hazardous Materials Safety Administration's and the Federal Railroad Administration's regulations for rail shipments require that rail cars fit physical and structural specifications. These specifications include thick tanks and pressure release devices. Rail cars also have to undergo inspections and maintenance, per these rules.

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The crew in charge of a hazardous materials train needs specialized training. And rail carriers need to have emergency response plans in case of a hazardous material spill.

Both truck and rail companies must follow regulations that require the proper classification, packaging and labeling of hazardous materials. The symbols on these labels let handlers and emergency responders know the potential risks the materials pose.

The Pipeline and Hazardous Materials Safety Administration's security regulations prevent or sabotage of hazardous materials. They make sure that only authorized people can access the shipments. These regulations may require background checks for workers, secure storage facilities, and that track and monitor hazardous material.

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Hazardous material shipments and incidents both have increased in the past 10 years. Anyone involved in the supply chain needs to understand hazardous material regulations.

Sticking to these rules helps get these materials from place to place safely. It also keeps safe those who handle them and minimizes the risk of accidents, injuries and environmental harm.The Conversation

Michael F. Gorman, Professor of Business Analytics and Operations Management, University of Dayton

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

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