Remote work is changing travel. Here’s what you need to know

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Now that remote work seems to be here to stay, the travel industry is seeing the effects.

This summer, 20% of travelers are planning to work while they’re on the road, NerdWallet reported, citing Deloitte data. Among those travelers, four out of five plan to prolong their trip because of flexible job schedules


Because remote workers can travel at any time, some travel trends could change dramatically, NerdWallet reported. 

For example, flights have historically been more expensive on weekends and cheaper during the week, but that could change now that more people are working remotely, the personal finance website reported.


Travel booking app Hopper has found that the cost of domestic flights on Sundays has risen 5.9% and domestic flights on Mondays has risen 2.97% this year compared to 2019, NerdWallet reported.

Meanwhile, flight prices have dropped by 3.04% on Fridays and by 1.6% on Saturdays, making Saturday a cheaper day to fly than Monday. 

Holiday travel could also change, since remote workers can take longer trips and avoid "peak" travel dates, according to NerdWallet. 

Remote work has also allowed people to save more for travel by moving to places with lower costs of living and tax incentives, NerdWallet reported. 

"Many travelers who have the opportunity are choosing to combine remote working with trips for a change of scene as well as maximizing PTO," Mark Crossey, a traveler expert at Skyscanner, told NerdWallet. 

"Workations allow people with flexible home and work lives to become ‘half tourists’ for a period of time," Crossey added. 

The Associated Press contributed to this report. 


Source: Remote work is changing travel. Here’s what you need to know

Airline staffing issues leading to more lost, unclaimed bags in airports

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The Unclaimed Baggage store in Scottsboro, Alabama, is full of items from lost or unclaimed luggage. 

"All my friends at college and stuff are so jealous of all of the stuff that I find here," said shopper Kami Willis.

Everything in the store is from bags that went unclaimed for at least 90 days. Owner Bryan Owens has run Unclaimed Baggage for some 50 years. He said he frequently has seen more bags coming in during busy travel periods, but not like this. 

"We have more product than ever right now," Owens said. "Both at and in our store."


FlightAware reported that airline staffing issues have sparked many of these luggage problems.


"With so many missing workers, so many fewer baggage handlers, what’s happening is a lot of these things are not getting to their destinations," said FlightAware spokeswoman Kathleen Bangs.

Unclaimed Baggage is getting more luggage from around the U.S., including from the closest major airport in Atlanta.


"Hartsfield is certainly a huge airport," Owens said.

"But, we’re seeing items come to us by the tractor-trailer load every week from all across America."

Source: Airline staffing issues leading to more lost, unclaimed bags in airports

The Terraforming Mars card game is as good as we’d hoped it would be

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The 2016 board game Terraforming Mars is an amazing title.

As evidence, I present the following image:

If a game this ugly can capture the hearts, minds, and continued attention of the devotees of the overcrowded board game market to become a modern classic, you know it’s something special.

And if a board game becomes popular, you can be sure of one thing: A card game version will eventually arrive. If that’s a hit, get ready for the dice version. And then, market willing, comes the roll-and-write version. That may sound like cynical resignation to cash-grabby companies endlessly returning to the same well, but these reimagined versions aren’t necessarily a bad thing. In fact, some of my favorite games are card or dice versions of “bigger” board games.

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Source: The Terraforming Mars card game is as good as we’d hoped it would be

How different cancer cells respond to drug-delivering nanoparticles

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Using nanoparticles to deliver cancer drugs offers a way to hit tumors with large doses of drugs while avoiding the harmful side effects that often come with chemotherapy. However, so far, only a handful of nanoparticle-based cancer drugs have been FDA-approved.

A new study from MIT and Broad Institute of MIT and Harvard researchers may help to overcome some of the obstacles to the development of nanoparticle-based drugs. The team’s analysis of the interactions between 35 different types of nanoparticles and nearly 500 types of cancer cells revealed thousands of biological traits that influence whether those cells take up different types of nanoparticles.

The findings could help researchers better tailor their drug-delivery particles to specific types of cancer, or design new particles that take advantage of the biological features of particular types of cancer cells.

“We are excited by our findings because it is really just the beginning — we can use this approach to map out what types of nanoparticles are best to target certain cell types, from cancer to immune cells and other kinds of healthy and diseased organ cells. We are learning how surface chemistry and other material properties play a role in targeting,” says Paula Hammond, an MIT Institute Professor, head of the Department of Chemical Engineering, and a member of MIT’s Koch Institute for Integrative Cancer Research.

Hammond is the senior author of the new study, which appears today in Science. The paper’s lead authors are Natalie Boehnke, an MIT postdoc who will soon join the faculty at the University of Minnesota, and Joelle Straehla, the Charles W. and Jennifer C. Johnson Clinical Investigator at the Koch Institute, an instructor at Harvard Medical School, and a pediatric oncologist at Dana-Farber Cancer Institute.

Cell-particle interactions

Hammond’s lab has previously developed many types of nanoparticles that can be used to deliver drugs to cells. Studies in her lab and others have shown that different types of cancer cells often respond differently to the same nanoparticles. Boehnke, who was studying ovarian cancer when she joined Hammond’s lab, and Straehla, who was studying brain cancer, also noticed this phenomenon in their studies.

The researchers hypothesized that biological differences between cells could be driving the variation in their responses. To figure out what those differences might be, they decided to pursue a large-scale study in which they could look at a huge number of different cells interacting with many types of nanoparticles.

Straehla had recently learned about the Broad Institute’s PRISM platform, which was designed to allow researchers to rapidly screen thousands of drugs on hundreds of different cancer types at the same time. With instrumental collaboration from Angela Koehler, an MIT associate professor of biological engineering, the team decided to try to adapt that platform to screen cell-nanoparticle interactions instead of cell-drug interactions.

“Using this approach, we can start thinking about whether there is something about a cell’s genotypic signature that predicts how many nanoparticles it will take up,” Boehnke says.

For their screen, the researchers used 488 cancer cell lines from 22 different tissues of origin. Each cell type is “barcoded” with a unique DNA sequence that allows researchers to identify the cells later on. For each cell type, extensive datasets are also available on their gene expression profiles and other biological characteristics.

On the nanoparticle side, the researchers created 35 particles, each of which had a core consisting of either liposomes (particles made from many fatty molecules called lipids), a polymer known as PLGA, or another polymer called polystyrene. The researchers also coated the particles with different types of protective or targeting molecules, including polymers such as polyethylene glycol, antibodies, and polysaccharides. This allowed them to study the influence of both the core composition and the surface chemistry of the particles.

Working with Broad Institute scientists, including Jennifer Roth, director of the PRISM lab, the researchers exposed pools of hundreds of different cells to one of 35 different nanoparticles. Each nanoparticle had a fluorescent tag, so the researchers could use a cell-sorting technique to separate the cells based on how much fluorescence they gave off after an exposure of either four or 24 hours.

Based on these measurements, each cell line was assigned a score representing its affinity for each nanoparticle. The researchers then used machine learning algorithms to analyze those scores along with all of the other biological data available for each cell line.

This analysis yielded thousands of features, or biomarkers, associated with affinity for different types of nanoparticles. Many of these markers were genes that code for the cellular machinery needed to bind particles, bring them into a cell, or process them. Some of these genes were already known to be involved in nanoparticle trafficking, but many others were new.

“We found some markers that we expected, and we also found much more that has really been unexplored. We're hoping that other people can use this dataset to help expand their view of how nanoparticles and cells interact,” Straehla says.

Particle uptake

The researchers picked out one of the biomarkers they identified, a protein called SLC46A3, for further study. The PRISM screen had shown that high levels of this protein correlated with very low uptake of lipid-based nanoparticles. When the researchers tested these particles in mouse models of melanoma, they found the same correlation. The findings suggest that this biomarker could be used to help doctors identify patients whose tumors are more likely to respond to nanoparticle-based therapies.

Now, the researchers are trying to uncover the mechanism of how SLC46A3 regulates nanoparticle uptake. If they could discover new ways to decrease cellular levels of this protein, that could help make tumors more susceptible to drugs carried by lipid nanoparticles. The researchers are also working on further exploring some of the other biomarkers they found.

This screening approach could also be used to investigate many other types of nanoparticles that the researchers didn’t look at in this study.

“The sky is the limit in terms of what other undiscovered biomarkers are out there that we just haven't captured because we haven't screened them,” Boehnke says. “Hopefully it’s an inspiration for others to start looking at their nanoparticle systems in a similar manner.”

The research was funded, in part, by SPARC funding to the Broad Institute, the Marble Center for Cancer Nanomedicine at the Koch Institute, and the Koch Institute Support (core) Grant from the National Cancer Institute.

Source: How different cancer cells respond to drug-delivering nanoparticles

Fabric + form = a mask that uniquely fits your face

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Form-fitting clothing is not always governed by sartorial choice. The global pandemic, for example, has underscored the need for face masks that effectively seal around the nose and mouth. But faces and their features differ from one person to the next and can render one-size-fits-all face masks less effective. Well-fitting masks have proved to be a sought-after accessory.

Lavender Tessmer, a doctoral candidate in MIT’s Department of Architecture, has developed a new active fiber and designed a process that — combined with a specific knit textile architecture — uses heat to activate a mask to conform to an individual’s face. With standard textile equipment and the new customization process, any manufacturer can create a customized mask.

Before coming to MIT in 2017, Tessmer had no formal introduction to textiles. She began working with Skylar Tibbits, associate professor in the Department of Architecture and founder of the Self-Assembly Lab, where programmable materials — simple materials that can be activated to sense, respond, and transform — are among its research topics. The following year, the lab purchased an industrial flatbed knitting machine, ubiquitous in textile manufacturing around the world, and Tessmer set to work learning how to operate it.

“It has a huge learning curve, and there are an infinite number of things you can do with a machine like this,” says Tessmer. 

Her early start with the knitting machine was prescient for the work to come.

A head start

A few years before the pandemic, Tibbits’s lab received a grant from Advanced Functional Fibers of America (AFFOA) to develop “smarter textiles” that would be able to sense, respond, and transform. The research led to a partnership with Ministry of Supply — a fashion company specializing in high-tech apparel — to develop a new system for “smart textiles.” Created by MIT graduates, Ministry of Supply uses temperature-regulating material to design and produce environmentally sustainable clothing geared to professionals.

In spring 2020, a confluence of events shifted their collaboration. The global pandemic forced businesses to close in March; the Department of Architecture called for proposals to fund research positions for students to work with faculty on “crisis-related research,” including design responses to the pandemic; and the need for masks to protect first responders and the general public became apparent. Tibbits’s research received department funding.

“Lavender was already trying to make textile apparel with a customized fit, so we could quickly transition to making customized masks,” says Tibbits. “But the main challenge with any customization is that you cannot make each mask unique. It becomes a factory logistics problem. You have to be able to mass-produce these. Customers don’t want to wait weeks or months for their unique mask.”

How, then, is a mass-produced mask tailored for an individual face?

“Lavender created the knit structure — the architecture — of the mask,” says Tibbits. “The material properties alone don’t lead to the behavior of precise transformation. It’s basically two- or three-dimensionally knitting structures, and with every single stitch you can change the structure and the materials.”

Tessmer also developed one of the two active fibers (the other was already commercially available) needed to respond to heat so the fabric could be controlled in a predictable way.

“There had to be a clear relationship between how much heat is applied, the method of applying it with the robot, and having a predictable result in the dimensional transformation of the fabric,” says Tessmer. “That was an iterative process between developing the multi-layered fabric, measuring its dimensional change, and then eventually being able to have the robot apply heat in a repeatable and predicable way.”

Already in the public realm were guidelines for existing ranges of human facial feature measurements. The starting shape of the mask is large enough for almost every face before it’s transformed and customized. From there, Tessmer input dimensions from an individual’s face and the knit masks were activated with a robotic arm outfitted with a heat gun that applies heat in specific patterns to tailor them precisely to the facial measurements.

Covid-driven need for masks

With their retail operations closed early in the pandemic, Ministry of Supply pivoted from making clothes to making face masks.

“The strength of Lavender and Skylar’s work is that it takes advantage of additive manufacturing techniques, which can be spun up for production very quickly,” says Gihan Amarasiriwardena ’11, a Ministry of Supply co-founder and the company’s president. “Working with the Self-Assembly Lab, we were able to design, test, and develop a mask in five days and have 4,000 masks produced in two weeks for health care workers due to our ability to use 3D computerized knitting. I think this will be a critical asset in being able to divert existing materials toward masks very quickly in the future.”

“The objective was to transform a mask to achieve the perfect fit for anyone’s face, which is a major challenge with masks and other pieces of clothing,” says Tibbits. “No one has really figured out how to do that, other than hiring a tailor or having lots of standard sizes that don’t fit perfectly.”

It is important to note that Tessmer and Tibbits’s work was focused on a mask’s fit, and not the properties required for a mask’s material to filter out airborne particles — although a standard filter could be included to enhance its efficacy. The masks are also reusable and washable.

“Our goal was better fibers and a controllable, repeatable process to create a custom-fit mask,” says Tessmer. “We created masks for nine different people to demonstrate how effective the process is.”

Last fall a paper they co-authored, “Personalized Knit Masks: Programmable Shape Change for Customized Fit,” provided instructions to create “truly customizable masks” that conform to the unique facial features of any individual. The Association for Computer Aided Design in Architecture (ACADIA) honored Tessmer and Tibbits with its Best Paper Award for this groundbreaking work.

“The award highlights the paper as exemplary, showcasing innovative research with substantial contribution to the described field,” noted the judges in their remarks. “Beyond demonstrating rigorous methods of research and disciplinary expertise, the paper is also well-written, bringing new insights to the ACADIA community and beyond.

The evolution of SARS-CoV-2 variants suggests the need for high-quality masks will persist, and the U.S. Centers for Disease Control continue to support their use. Amarasiriwardena believes there will continue to be consumer interest and need for masks, if only seasonally when people are indoors more frequently. He says the fit and comfort of a mask is the second question customers ask, after the efficacy of the filter media.

“Overall efficacy is tied to fit, which is unlocked by personalized manufacturing,” says Amarasiriwardena. “The Self-Assembly Lab has really been pushing the bounds of additive manufacturing, and their recent work in textiles marries their expertise in ‘hacking’ CAD-CAM flows to create truly novel soft goods. While much of the attention has focused on 3D-printing hard goods, their innovation in textiles shows a broad application of the self-assembly technology.”

Tessmer says the masks were a great case study because they were a sought-after accessory the last few years, and there have been noticeable problems with how masks fit. She would like to apply the process to other types of garments and accessories, such as sweaters and shoes. 

“At the end of every project there are always things you find that need to be improved upon,” Tessmer says. “There’s a lot of future fabric development, for example. But I’m happy with the project because it is a working proof-of-concept for my idea, and I’m confident that it works.”

Source: Fabric + form = a mask that uniquely fits your face

Cartoon Cautionary Tales

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Edward Steed animates some of life’s most crucial lessons.

Source: Cartoon Cautionary Tales


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Top 10 AI marketing tools

 The marketing industry is turning to artificial intelligence (AI) as a way to save time and execute smarter, more personalized campaigns. 61% of marketers say AI software is the most important aspect of their data strategy.

  If you’re late to the AI party, don’t worry. It’s easier than you think to start leveraging artificial intelligence tools in your marketing strategy. Here are 11 AI marketing tools every marketer should start using today.

1. Jasper Ai(Formerly known as Jarvis)

Jasper is a content writing and content generation tool that uses artificial intelligence to identify the best words and sentences for your writing style and medium in the most efficient, quick, and accessible way.

Key Features

  •  It's trusted by 50,000+ marketers for creating engaging marketing campaigns, ad copy, blog posts, and articles within minutes which would traditionally take hours or days. Special Features:
  • Blog posts have been optimized for search engines and rank high on Google and other search engines. This is a huge plus for online businesses that want to generate traffic to their website through content marketing.
  • 99.9% Original Content and guarantees that all content it generates will be original, so businesses can focus on their online reputation rather than worrying about penalties from Google for duplicate content.
  • Long-Form Article Writing – is also useful for long-form writing, allowing users to create articles of up to 10,000 words without any difficulty. This is ideal for businesses that want to produce in-depth content that will capture their audience’s attention.
Wait! I've got a pretty sweet deal for you. Sign up through the link below, and you'll get (10k Free Credits)

2. Personalize

 Personalize is an AI-powered technology that helps you identify and produce highly targeted sales and marketing campaigns by tracking the products and services your contacts are most interested in at any given time. The platform uses an algorithm to identify each contact’s top three interests, which are updated in real-time based on recent site activity.

Key Features

  • Identifies  top three interests based on metrics like time on page, recency, and frequency of each contact
  • Works with every ESP and CRM
  • Easy to get up and running in days
  • Enterprise-grade technology at a low cost for SMBs

3. Seventh Sense

  Seventh Sense provides behavioral analytics that helps you win attention in your customers’ overcrowded email inboxes. Choosing the best day and time to send an email is always a gamble. And while some days of the week generally get higher open rates than others, you’ll never be able to nail down a time that’s best for every customer. Seventh Sense eases your stress of having to figure out the perfect send-time and day for your email campaigns. The AI-based platform figures out the best timing and email frequency for each contact based on when they’re opening emails. The tool is primarily geared toward HubSpot and Marketo customers 

Key Features 

  • AI determines the best send-time and email frequency for each contact
  • Connects with HubSpot and Marketo

4. Phrasee

  Phrasee uses artificial intelligence to help you write more effective subject lines. With its AI-based Natural Language Generation system, Phrasee uses data-driven insights to generate millions of natural-sounding copy variants that match your brand voice. The model is end-to-end, meaning when you feed the results back to Phrasee, the prediction model rebuilds so it can continuously learn from your audience.

Key Features 

  • Instantly generates millions of human-sounding, brand-compliant copy variants
  • Creates tailored language models for every customer
  • Learns what your audience responds to and rebuilds the prediction model every time

5. Hubspot Seo

  HubSpot Search Engine Optimization (SEO) is an integral tool for the Human Content team. It uses machine learning to determine how search engines understand and categorize your content. HubSpot SEO helps you improve your search engine rankings and outrank your competitors. Search engines reward websites that organize their content around core subjects, or topic clusters. HubSpot SEO helps you discover and rank for the topics that matter to your business and customers.

Key Features 

  • Helps you discover and rank topics that people are searching for
  • Provides suggestions for your topic clusters and related subjects
  • Integrates with all other HubSpot content tools to help you create a well-rounded content strategy

 6. Evolve AI

  When you’re limited to testing two variables against each other at a time, it can take months to get the results you’re looking for. Evolv AI lets you test all your ideas at once. It uses advanced algorithms to identify the top-performing concepts, combine them with each other, and repeat the process to achieve the best site experience.

Key Features 

  • Figures out which content provides the best performance
  • Lets you test multiple ideas in a single experiment instead of having to perform many individual tests over a long period
  • Lets you try all your ideas across multiple pages for full-funnel optimization
  • Offers visual and code editors

7. Acrolinx

  Acrolinx is a content alignment platform that helps brands scale and improves the quality of their content. It’s geared toward enterprises – its major customers include big brands like Google, Adobe, and Amazon - to help them scale their writing efforts. Instead of spending time chasing down and fixing typos in multiple places throughout an article or blog post, you can use Acrolinx to do it all right there in one place. You start by setting your preferences for style, grammar, tone of voice, and company-specific word usage. Then, Acrolinx checks and scores your existing content to find what’s working and suggest areas for improvement. The platform provides real-time guidance and suggestions to make writing better and strengthen weak pages.

Key features

  • Reviews and scores existing content to ensure it meets your brand guidelines
  • Finds opportunities to improve your content and use automation to shorten your editorial process.
  • Integrates with more than 50 tools and platforms, including Google Docs, Microsoft Word, WordPress, and most web browsers.

8. MarketMuse 

MarketMuse uses an algorithm to help marketers build content strategies. The tool shows you where to target keywords to rank in specific topic categories, and recommends keywords you should go after if you want to own particular topics. It also identifies gaps and opportunities for new content and prioritizes them by their probable impact on your rankings. The algorithm compares your content with thousands of articles related to the same topic to uncover what’s missing from your site.

Key features:

  • The built-in editor shows how in-depth your topic is covered and what needs improvement
  • Finds gaps and opportunities for new content creation, prioritized by their probable impact and your chance of ranking

9. Copilot

Copilot is a suite of tools that help eCommerce businesses maintain real-time communication with customers around the clock at every stage of the funnel. Promote products, recover shopping carts and send updates or reminders directly through Messenger.

Key features: 

  • Integrate Facebook Messenger directly with your website, including chat history and recent interactions for a fluid customer service experience 
  • Run drip messenger campaigns to keep customers engaged with your brand
  • Send abandoned carts, out-of-stock, restock, preorder, order status, and shipment notifications to contacts 
  • Send branded images, promotional content, or coupon codes to those who opt in
  • Collect post-purchase feedback, reviews, and customer insight
  • Demonstrate social proof on your website with a widget, or push automatic Facebook posts sharing recent purchases
  • Display a promotional banner on your website to capture contacts instantly

10. Yotpo

Yotpo’s deep learning technology evaluates your customers’ product reviews to help you make better business decisions. It identifies key topics that customers mention related to your products—and their feelings toward them. The AI engine extracts relevant reviews from past buyers and presents them in smart displays to convert new shoppers. Yotpo also saves you time moderating reviews. The AI-powered moderation tool automatically assigns a score to each review and flags reviews with negative sentiment so you can focus on quality control instead of manually reviewing every post.

Key features:

  • Makes it easy for shoppers to filter reviews and find the exact information they’re looking for
  • Analyzes customer feedback and sentiments to help you improve your products
  • Integrates with most leading eCommerce platforms, including BigCommerce, Magento, and Shopify.

11. Albert AI

  Albert is a self-learning software that automates the creation of marketing campaigns for your brand. It analyzes vast amounts of data to run optimized campaigns autonomously, allowing you to feed in your own creative content and target markets, and then use data from its database to determine key characteristics of a serious buyer. Albert identifies potential customers that match those traits, and runs trial campaigns on a small group of customers—with results refined by Albert himself—before launching it on a larger scale.

  Albert plugs into your existing marketing technology stack, so you still have access to your accounts, ads, search, social media, and more. Albert maps tracking and attribution to your source of truth so you can determine which channels are driving your business.

Key features:

  • Breaks down large amounts of data to help you customize campaigns
  • Plugs into your marketing technology stack and can be used across diverse media outlets, including email, content, paid media, and mobile

Final Saying

There are many tools and companies out there that offer AI tools, but this is a small list of resources that we have found to be helpful. If you have any other suggestions, feel free to share them in the comments below this article. As marketing evolves at such a rapid pace, new marketing strategies will be invented that we haven't even dreamed of yet. But for now, this list should give you a good starting point on your way to implementing AI into your marketing mix.

Note: This article contains affiliate links, meaning we make a small commission if you buy any premium plan from our link.


Microparticles could be used to deliver “self-boosting” vaccines

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Most vaccines, from measles to Covid-19, require a series of multiple shots before the recipient is considered fully vaccinated. To make that easier to achieve, MIT researchers have developed microparticles that can be tuned to deliver their payload at different time points, which could be used to create “self-boosting” vaccines.

In a new study, the researchers describe how these particles degrade over time, and how they can be tuned to release their contents at different time points. The study also offers insights into how the contents can be protected from losing their stability as they wait to be released.

Using these particles, which resemble tiny coffee cups sealed with a lid, researchers could design vaccines that would need to be given just once, and would then “self-boost” at a specified point in the future. The particles can remain under the skin until the vaccine is released and then break down, just like resorbable sutures.

This type of vaccine delivery could be particularly useful for administering childhood vaccinations in regions where people don’t have frequent access to medical care, the researchers say.

“This is a platform that can be broadly applicable to all types of vaccines, including recombinant protein-based vaccines, DNA-based vaccines, even RNA-based vaccines,” says Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “Understanding the process of how the vaccines are released, which is what we described in this paper, has allowed us to work on formulations that address some of the instability that could be induced over time.”

This approach could also be used to deliver a range of other therapeutics, including cancer drugs, hormone therapy, and biologic drugs, the researchers say.

Jaklenec and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, are the senior authors of the new study, which appears today in Science Advances. Morteza Sarmadi, a research specialist at the Koch Institute and recent MIT PhD recipient, is the lead author of the paper.

Staggered drug release

The researchers first described their new microfabrication technique for making these hollow microparticles in a 2017 Science paper. The particles are made from PLGA, a biocompatible polymer that has already been approved for use in medical devices such as implants, sutures, and prosthetic devices.

To create cup-shaped particles, the researchers create arrays of silicon molds that are used to shape the PLGA cups and lids. Once the array of polymer cups has been formed, the researchers employed a custom-built, automated dispensing system to fill each cup with a drug or vaccine. After the cups are filled, the lids are aligned and lowered onto each cup, and the system is heated slightly until the cup and lid fuse together, sealing the drug inside.

This technique, called SEAL (StampEd Assembly of polymer Layers), can be used to produce particles of any shape or size. In a paper recently published in the journal Small Methods, lead author Ilin Sadeghi, an MIT postdoc, and others created a new version of the technique that allows for simplified and larger-scale manufacturing of the particles.

In the new Science Advances study, the researchers wanted to learn more about how the particles degrade over time, what causes the particles to release their contents, and whether it might be possible to enhance the stability of the drugs or vaccines carried within the particles.

“We wanted to understand mechanistically what’s happening, and how that information can be used to help stabilize drugs and vaccines and optimize their kinetics,” Jaklenec says.

Their studies of the release mechanism revealed that the PLGA polymers that make up the particles are gradually cleaved by water, and when enough of these polymers have broken down, the lid becomes very porous. Very soon after these pores appear, the lid breaks apart, spilling out the contents.

“We realized that sudden pore formation prior to the release time point is the key that leads to this pulsatile release,” Sarmadi says. “We see no pores for a long period of time, and then all of a sudden we see a significant increase in the porosity of the system.”

The researchers then set out to analyze how a variety of design parameters, include the size and shape of the particles and the composition of the polymers used to make them, affect the timing of drug release.

To their surprise, the researchers found that particle size and shape had little effect on drug release kinetics. This sets the particles apart from most other types of drug delivery particles, whose size plays a significant role in the timing of drug release. Instead, the PLGA particles release their payload at different times based on differences in the composition of the polymer and the chemical groups attached the ends of the polymers.

“If you want the particle to release after six months for a certain application, we use the corresponding polymer, or if we want it to release after two days, we use another polymer,” Sarmadi says. “A broad range of applications can benefit from this observation.”

Stabilizing the payload

The researchers also investigated how changes in environmental pH affect the particles. When water breaks down the PLGA polymers, the byproducts include lactic acid and glycolic acid, which make the overall environment more acidic. This can damage the drugs carried within the particles, which are usually proteins or nucleic acids that are sensitive to pH.

In an ongoing study, the researchers are now working on ways to counteract this increase in acidity, which they hope will improve the stability of the payload carried within the particles.

To help with future particle design, the researchers also developed a computational model that can take many different design parameters into account and predict how a particular particle will degrade in the body. This type of model could be used to guide the development of the type of PLGA particles that the researchers focused on in this study, or other types of microfabricated or 3D-printed particles or medical devices.

The research team has already used this strategy to design a self-boosting polio vaccine, which is now being tested in animals. Usually, the polio vaccine has to be given as a series of two to four separate injections.

“We believe these core shell particles have the potential to create a safe, single-injection, self-boosting vaccine in which a cocktail of particles with different release times can be created by changing the composition. Such a single injection approach has the potential to not only improve patient compliance but also increase cellular and humoral immune responses to the vaccine,” Langer says.

This type of drug delivery could also be useful for treating diseases such as cancer. In a 2020 Science Translational Medicine study, the researchers published a paper in which they showed that they could deliver drugs that stimulate the STING pathway, which promotes immune responses in the environment surrounding a tumor, in several mouse models of cancer. After being injected into tumors, the particles delivered several doses of the drug over several months, which inhibited tumor growth and reduced metastasis in the treated animals.

The research was funded by the Bill and Melinda Gates Foundation.

Source: Microparticles could be used to deliver “self-boosting” vaccines

Your friendly neighborhood architect

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Justin Brazier didn’t always know that his path in life would take him right back home.

Brazier grew up with two brothers in a tight-knit family in Randolph, Massachusetts, two cities south of Boston. His parents, who are Haitian immigrants, had also grown up in the Boston area and met each other there.

From a young age, Brazier loved to draw. But when it came time for college, he didn’t think he could get a viable job as an artist. Instead, he searched for other exciting careers, hopping between colleges in and out of the Boston area and cycling through numerous majors, from engineering to business to chemistry. But he had no luck with finding a match.

Finally, after years of searching, “I bit the bullet to pursue art,” figuring that even “if I don’t make any money, at least I’ll be happy,” he says. Brazier returned to Boston to study at the Massachusetts College of Art and Design. At first, he pursued industrial design with the goal of designing sneakers. But then, some of his professors encouraged him to look into architecture, where he could develop a broader skill set. “I took some classes and everything clicked,” he says.

Brazier’s interest in architecture solidified during his undergraduate studies when he joined the Farmers Collaborative, a Boston-based group that works with city officials to turn vacant lots into urban agricultural centers. Brazier started off designing garden grow beds for the collaborative’s projects, working with co-founders CJ Valerus and Leon David. These grow beds became a food source in the Boston community and helped ease food insecurity. Through this work and his studies, “I realized the ability architects have to shape the environment. The design of greenhouses and farming structures can connect people with their history and culture,” he says.

After graduating, Brazier continued to work with the Farmers Collaborative, while keeping a full-time job. With only a bachelor’s degree in architecture, though, he was limited in how far he could push projects forward. To fully realize a project on his own, he would need a professional license. Because of this, “I always knew I wanted to go to grad school to become a full architect,” Brazier says. After taking a couple of years off from school to work, he joined MIT’s MArch program.

Brazier plans to use his expertise as a licensed architect to help communities, especially those of color, transform neighborhoods through urban agriculture and food sovereignty. This goal, rooted in his childhood and family background, is “really important to me,” he says.

A new community greenhouse underway

While pursuing his master’s, Brazier has stayed involved with the Farmers Collaborative. He is currently working on a project with Velarus and David to build a year-round greenhouse in Mattapan, a neighborhood of Boston with a large Haitian population, where his dad grew up. Brazier has also brought professor and licensed architect Sheila Kennedy, his mentor at MIT, on board to help with the project.

A major goal of the greenhouse project is to improve food security in Mattapan through urban agriculture. Brazier is taking a holistic approach to the project, informed by the neighborhood’s input. “We’re thinking about the agricultural process in a full cycle, where we have pollination to food growth to composting,” he says. Besides the main greenhouse, the community space will have a bee apiary, several outside grow beds, and a composting area.

The space will also serve as a place for the community to get together. People can relax in the patio seating area or host an open-air farmer’s market out back. Brazier also hopes to introduce educational programs in the space for kids to learn about agriculture and climate. “We want to create a space that contributes to the overall sustainability of the neighborhood, culturally and socially,” Brazier says.

The greenhouse will sit on a corner lot on the highly trafficked Morton Street. The lot is a short five-minute walk from the street’s major intersection with Blue Hill Avenue. “It’s a prominent area that can really show off what the community is able to do,” Brazier says.

Prior to the Morton Street project, Brazier worked on a similar project with the collaborative to build a greenhouse in Dorchester, a neighborhood adjacent to Mattapan that is also home to a large Black community. The previous project, coordinated by architect Wyly Brown and graduate students from MassArt, called the HERO Hope Garden, is located on Geneva Avenue in the heart of Dorchester. At the center of the Garden is a wooden greenhouse with an angled slatted roof, flanked by several grow beds and open patio seating with a painted mural backdrop. “Everyone loves it,” Brazier says. “It’s helped the community to grow food to stave off food insecurities, especially during Covid.”

Brazier and the Collaborative are using the HERO Hope Garden as a template for the Morton Street project, carrying over its successes and making strategic improvements. For example, although the garden’s wooden greenhouse is fully enclosed, animals and cold winter air still find their way inside. For the Morton Street project, “it’s going to be steel construction, which is a lot more robust,” he says. “And it’s going to be completely weather tight to work through all seasons” for increased food production.

To make this community project possible, the city of Boston is providing funding through the Mayor’s Office of Housing and the Community Preservation Act. But “to realize the project in full,” there’s still “a little bit of a funding gap,” Brazier says. He and the collaborative are currently looking for additional funding to close this gap and ensure the community can have all of the project’s planned features.

In the meantime, with most of the funding nailed down, construction on the Morton Street project will start this summer, with plans for completion next summer.

Empowering communities to bring their ideas to life

While Brazier has been heavily involved with urban agriculture projects these past few years, he ultimately sees himself playing a broader role in the community. He’s noticed that when people, especially those of color, have ideas to upgrade their neighborhoods, they often struggle to push their ideas forward. “People want to propose different things to the city but don’t have the skill set or language” and need an architect’s help, he says. But for many people of color, an architect “feels like somebody they can’t really approach” because they don’t know any or can’t identify with them.

That’s where Brazier comes in. Having roots in the Greater Boston area makes him more approachable to people in these communities. Brazier has gotten calls to help put together proposals for the Mattapan area and beyond, including turning an abandoned building into a café, putting up art installations in alleyways, and conducting design studies for first time developers looking to build local ownership within their neighborhoods. His plans and renderings have helped people start conversations with city officials about their ideas, opening doors even if the projects don’t pan out.

Last year, some people Brazier had grown up with reached out to him for help with renovating their sneaker store in Randolph. Brazier worked on the interior design of the store, named Kerms. Located near Randolph High School, Kerms now sets an inspirational example for kids in the community, showing them that “they can stay in Randolph and have ownership,” he says.

Brazier is happy that he’s in a place where people feel comfortable asking him for design help that he can provide. At the end of the day, all he wants to do is “empower people to develop their own environments and put their fingerprints on their own neighborhood,” he says.

Source: Your friendly neighborhood architect

How a shape-shifting receptor influences cell growth

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Receptors found on cell surfaces bind to hormones, proteins, and other molecules, helping cells respond to their environment. MIT chemists have now discovered how one of these receptors changes its shape when it binds to its target, and how those changes trigger cells to grow and proliferate.

This receptor, known as epidermal growth factor receptor (EGFR), is overexpressed in many types of cancer and is the target of several cancer drugs. These drugs often work well at first, but tumors can become resistant to them. Understanding the mechanism of these receptors better may help researchers design drugs that can evade that resistance, says Gabriela Schlau-Cohen, an associate professor of chemistry at MIT.

“Thinking about more general mechanisms to target EGFR is an exciting new direction, and gives you a new avenue to think about possible therapies that may not evolve resistance as easily,” she says.

Schlau-Cohen and Bin Zhang, the Pfizer-Laubach Career Development Assistant Professor of Chemistry, are the senior authors of the study, which appears today in Nature Communications. The paper’s lead authors are MIT graduate student Shwetha Srinivasan and former MIT postdoc Raju Regmi.

Shape-changing receptors

The EGF receptor is one of many receptors that help control cell growth. Found on most types of mammalian epithelial cells, which line body surfaces and organs, it can respond to several types of growth factors in addition to EGF. Some types of cancer, especially lung cancer and glioblastoma, overexpress the EGF receptor, which can lead to uncontrolled growth.

Like most cell receptors, the EGFR spans the cell membrane. An extracellular region of the receptor interacts with its target molecule (also called a ligand); a transmembrane section is embedded within the membrane; and an intracellular section interacts with cellular machinery that controls growth pathways.

The extracellular portion of the receptor has been analyzed in detail, but the transmembrane and intracellular sections have been difficult to study because they are more disordered and can’t be crystallized.

About five years ago, Schlau-Cohen set out to try to learn more about those lesser-known structures. Her team embedded the proteins in a special type of self-assembling membrane called a nanodisc, which mimics the cell membrane. Then, she used single molecule FRET (fluorescence resonance energy transfer) to study how the conformation of the receptor changes when it binds to EGF.

FRET is commonly used to measure tiny distances between two fluorescent molecules. The researchers labeled the nanodisc membrane and the end of the intracellular tail of the protein with two different fluorophores, which allowed them to measure the distance between the protein tail and the cell membrane, under a variety of circumstances.

To their surprise, the researchers found that EGF binding led to a major change in the conformation of the receptor. Most models of receptor signaling involve interaction of multiple transmembrane helices to bring about large-scale conformational changes, but the EGF receptor, which has only a single helical segment within the membrane, appears to undergo such a change without interacting with other receptor molecules.

“The idea of a single alpha helix being able to transduce such a large conformational rearrangement was really surprising to us,” Schlau-Cohen says.

Molecular modeling

To learn more about how this shape change would affect the receptor’s function, Schlau-Cohen’s lab teamed up with Zhang, whose lab does computer simulations of molecular interactions. This kind of modeling, known as molecular dynamics, can model how a molecular system changes over time.

The modeling showed that when the receptor binds to EGF, the extracellular segment of the receptor stands up vertically, and when the receptor is not bound, it lies flat against the cell membrane. Similar to a hinge closing, when the receptor falls flat, it tilts the transmembrane segment and pulls the intracellular segment closer to the membrane. This blocks the intracellular region of the protein from being able to interact with the machinery needed to launch cell growth. EGF binding makes those regions more available, helping to activate growth signaling pathways.

The researchers also used their model to discover that positively charged amino acids in the intracellular segment, near the cell membrane, are key to these interactions. When the researchers mutated those amino acids, switching them from charged to neutral, ligand binding no longer activated the receptor.

“There’s a nice consistency we can see between the simulation and experiment,” Zhang says. “With the molecular dynamics simulations, we can figure out what are the amino acids that are essential for the coupling, and quantify the role of different amino acids. Then Gabriela showed that those predictions turned out to be correct.”

The researchers also found that cetuximab, a drug that binds to the EGF receptor, prevents this conformational change from occurring. Cetuximab has shown some success in treating patients with colorectal or head and neck cancer, but tumors can become resistant to it. Learning more about the mechanism of how EGFR responds to different ligands could help researchers to design drugs that might be less likely to lead to resistance, the researchers say.

The research was funded, in part, by the National Institutes of Health, including a Directors New Innovator Award.

Source: How a shape-shifting receptor influences cell growth

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