Researchers from Georgia Tech’s College of Engineering have developed a novel and flexible solution to address the problem. Their additively manufactured tile-based approach can construct on-demand, massively scalable arrays of 5G+ (5G/Beyond 5G)enabled smart skins with the potential to enable intelligence on nearly any surface or object. The study, recently published in Scientific Reports, describes the approach, which is not only much easier to scale and customize than current practices, but features no performance degradation whenever flexed or scaled to a very large number of tiles.

“Typically, there are a lot of smaller wireless network systems working together, but they are not scalable. With the current techniques, you can’t increase, decrease, or direct bandwidth, especially for very large areas,” said Tentzeris. “Being able to utilize and scale this novel tile-based approach makes this possible.”

Tentzeris says his team’s modular application equipped with 5G+ capability has the potential for immediate, large-scale impact as the telecommunications industry continues to rapidly transition to standards for faster, higher capacity, and lower latency communications.

Building the Tiles

In Georgia Tech’s new approach, flexible and additively manufactured tiles are assembled onto a single, flexible underlying layer. This allows tile arrays to be attached to a multitude of surfaces. The architecture also allows for very large 5G+ phased/electronically steerable antenna array networks to be installed on-the-fly. According to Tentzeris, attaching a tile array to an unmanned aerial vehicle (UAV) is even a possibility to surge broadband capacity in low coverage areas.

In the study, the team fabricated a proof-of-concept, flexible 5×5-centimeter tile array and wrapped it around a 3.5-centimeter radius curvature. Each tile includes an antenna subarray and an integrated, beamforming integrated circuit on an underlying tiling layer to create a smart skin that can seamlessly interconnect the tiles into very large antenna arrays and massive multiple-input multiple-outputs (MIMOs) — the practice of housing two or more antennas within a single wireless device. Tile-based array architectures on rigid surfaces with single antenna elements have been researched before, but do not include the modularity, additive manufacturability, or flexible implementation of the Georgia Tech design.

The proposed modular tile approach means tiles of identical sizes can be manufactured in large quantities and are easily replaceable, reducing the cost of customization and repairs. Essentially, this approach combines removable elements, modularity, massive scalability, low cost, and flexibility into one system.

5G+ is Just the Beginning

While the tiling architecture has demonstrated the ability to greatly enhance 5G+ technologies, its combination of flexible and conformal capabilities has the potential to be applied in numerous different environments, the Georgia Tech team says.

“The shape and features of each tile scale can be singular and can accommodate different frequency bands and power levels,” said Tentzeris. “One could have communications capabilities, another sensing capabilities, and another could be an energy harvester tile for solar, thermal, or ambient RF energy. The application of the tile framework is not limited to communications.”

Internet of Things, virtual reality, as well as smart manufacturing/Industry 4.0 — a technology-driven approach that utilizes internet-connected “intelligent” machinery to monitor and fully automate the production process — are additional areas of application the team is excited to explore.

“The tile-architecture’s mass scalability makes its applications particularly diverse and virtually ubiquitous. From structures the size of dams and buildings, to machinery or cars, down to individual health-monitoring wearables,” said Tentzeris. “We’re moving in a direction where everything will be covered in some type of a wireless conformal smart skin encompassing a communication system or antenna that allows for effective monitoring.”

The team now looks forward to testing the approach outside the lab on large, real-world structures. They are currently working on the fabrication of much larger, fully inkjet-printed tile arrays (256+ elements) that will be presented at the upcoming International Microwave Symposium (IEEE IMS 2022) — the flagship IEEE conference in RF and microwave engineering. The IMS presentation will introduce a new tile-based large-area architecture version that will allow assembly of customizable tile arrays in a rapid and low-cost fashion for numerous conformal platforms and 5G+ enabled applications.

The HIV epidemic has been overlooked during the COVID-19 pandemic but represents a critical and ongoing threat to human health with an estimated 1.5 million new infections in the last year alone.

Drug developers and research teams have been searching for cures and new treatment modalities for HIV for over 40 years but are limited by their understanding of how the virus establishes infection in the human body. How does this small, unassuming virus with only 12 proteins — and a genome only a third of the size of SARS-CoV-2 — hijack the body’s cells to replicate and spread across systems?

A cross-disciplinary team at Northwestern sought to answer that very question.

In the team’s new study, published today (April 1) in the journal Nature Communications, scientists used a new CRISPR gene-editing approach to identify human genes that were important for HIV infection in the blood, finding 86 genes that may play a role in the way HIV replicates and causes disease, including over 40 that have never been looked at in the context of HIV infection.

The study proposes a new map for understanding how HIV integrates into our DNA and establishes a chronic infection.

“The existing drug treatments are one of our most important tools in fighting the HIV epidemic and have been amazingly effective at suppressing viral replication and spread,” said Northwestern’s Judd Hultquist, a co-corresponding author. “But these treatments aren’t curative, so individuals living with HIV have to follow a strict treatment regimen that requires continual access to good affordable health care — that’s simply not the world we live in.”

Hultquist said with more understanding of how the virus replicates, treatments could one day become cures.

Hultquist is associate director of the Center for Pathogen Genomics and Microbial Evolution at Northwestern University Feinberg School of Medicine and serves as an assistant professor of medicine in infectious diseases at Feinberg.

A method without compromise

Before now, studies have relied on the use of immortalized human cancer cells (like HeLa cells) as models to study how HIV replicates in the lab. While these cells are easy to manipulate in the lab, they are imperfect models of human blood cells. Additionally, most of these studies use technology to turn down the expression of certain genes, but not turn them off entirely as with CRISPR, meaning scientists can’t always clearly determine if a gene was involved in helping or suppressing viral replication.

“With the CRISPR system, there’s no intermediary — the gene is on or off,” Hultquist said. “This capability to turn genes on and off in cells isolated directly from human blood is a game changer — this new assay is the most faithful representation of what’s happening in the body during HIV infection that we could easily study in the lab.”

In the study, T cells — the major cell type targeted by HIV — were isolated from donated human blood, and hundreds of genes were knocked out using CRISPR-Cas9 gene editing. The “knock-out” cells were then infected with HIV and analyzed. Cells that lost a gene important for viral replication showed decreased infection, while cells that lost an antiviral factor showed an increase in infection.

From there, the team validated the identified factors by selectively knocking them out in new donors, where they found a nearly even break of newly discovered pathways and well-researched ones.

Moving toward a cure for HIV

Hultquist said their findings represented a “perfect split” of novel and known factors to know they were doing something right.

“This is a really great proof-of-concept that the steps and processes that we took to perform the study were robust and well thought out,” Hultquist said. “That nearly half of the genes we found were previously discovered increases confidence in our dataset. The exciting part is that over half — 46 — of these genes had never before been looked at in the context of HIV infection, so they represent new potential therapeutic avenues to look into.”

The team is excited about further developing this technology to enable genome-wide screening where they independently knock out or turn on every gene in the human genome to identify all potential HIV host factors. These data would represent a critical piece in the puzzle, which would bring them even closer to curative strategies.

The study was a collaboration between Hultquist at Northwestern and Alexander Marson and Nevan Krogan at the University of California, San Francisco.

This research was supported by a Mathilde Krim amfAR grant using funds raised by generationCURE (109504-61-RKRL); NIH/NIGMS funding for the HIV Accessory & Regulatory Complexes (HARC) Center (P50 GM082250); NIH funding for the study of innate immune responses to intracellular pathogens (R01 AI120694 & P01 AI063302); NIH funding for the Third Coast Center for AIDS Research (P30 AI117943); NIH funding for the UCSF-Gladstone Institute of Virology & Immunology Center for AIDS Research; NIH funding for the UCSF Medical Scientist Training Program; several NIH/NIAID grants for HIV research (K22 AI136691, R01 AI165236 and R01 AI150998); and an NIH/NIDA grant (DP2 DA042423-01).

A new study now supports this idea, which Dudley calls the “drunken monkey” hypothesis.

The study was led by primatologist Christina Campbell of California State University, Northridge (CSUN), and her graduate student Victoria Weaver, who collected fruit eaten and discarded by black-handed spider monkeys (Ateles geoffroyi) in Panama. They found that the alcohol concentration in the fruit was typically between 1% and 2% by volume, a by-product of natural fermentation by yeasts that eat sugar in ripening fruit.

Moreover, the researchers collected urine from these free-ranging monkeys and found that the urine contained secondary metabolites of alcohol. This result shows that the animals were actually utilizing the alcohol for energy — it wasn’t just passing through their bodies.

“For the first time, we have been able to show, without a shadow of a doubt, that wild primates, with no human interference, consume fruit-containing ethanol,” said Campbell, a CUSN professor of anthropology who obtained her Ph.D. in anthropology from Berkeley in 2000. “This is just one study, and more need to be done, but it looks like there may be some truth to that ‘drunken monkey’ hypothesis — that the proclivity of humans to consume alcohol stems from a deep-rooted affinity of frugivorous (fruit-eating) primates for naturally-occurring ethanol within ripe fruit.”

Dudley laid out evidence for his idea eight years ago in the book, The Drunken Monkey: Why We Drink and Abuse Alcohol. Measurements showed that some fruits known to be eaten by primates have a naturally high alcohol content of up to 7%. But at the time, he did not have data showing that monkeys or apes preferentially sought out and ate fermented fruits, or that they digested the alcohol in the fruit.

For the newly reported study, the CSUN researchers teamed up with Dudley and UC Berkeley graduate student Aleksey Maro to analyze the alcohol content in the fruits. Maro is conducting a parallel study of the alcohol content in the fruit-based diet of chimpanzees in Uganda and the Ivory Coast.

“It (the study) is a direct test of the drunken monkey hypothesis,” said Dudley, UC Berkeley professor of integrative biology. “Part one, there is ethanol in the food they’re eating, and they’re eating a lot of fruit. Then, part two, they’re actually metabolizing alcohol — secondary metabolites, ethyl glucuronide and ethyl sulfate are coming out in the urine. What we don’t know is how much of it they’re eating and what the effects are behaviorally and physiologically. But it’s confirmatory.”

The study, which appeared this month in the journal Royal Society Open Science, was conducted at a field site, Barro Colorado Island in Panama, where Dudley has often conducted research and where he first began thinking about the role of ethanol in animal diets and how that might play into our enjoyment and abuse of alcohol.

The researchers found that the fruit that spider monkeys sniffed and took a bite out of routinely had alcohol concentrations of between 1% and 2%, about half the concentration of low-alcohol brews The ripe fruits they collected were from the jobo tree, Spondias mombin, and were a major component of the spider monkey diet. But the fruit also has been used for millennia by Indigenous human populations throughout Central and South America to make chicha, a fermented alcoholic beverage.

The researchers also collected urine from six spider monkeys. Five of the samples contained secondary metabolites of ethanol.

“The monkeys were likely eating the fruit with ethanol for the calories,” Campbell said. “They would get more calories from fermented fruit than they would from unfermented fruit. The higher calories mean more energy.”

Dudley said that he doubts that the monkeys feel the inebriating effects of alcohol that humans appreciate.

“They’re probably not getting drunk, because their guts are filling before they reach inebriating levels,” he said. “But it is providing some physiological benefit. Maybe, also, there’s an anti-microbial benefit within the food that they’re consuming, or the activity of the yeast and the microbes may be predigesting the fruit. You can’t rule that out.”

The need for the monkeys’ high caloric intake may similarly have influenced human ancestors’ decisions when choosing which fruit to eat, Campbell said.

“Human ancestors may also have preferentially selected ethanol-laden fruit for consumption, given that it has more calories,” she said. “Psychoactive and hedonic effects of ethanol may similarly result in increased consumption rates and caloric gain.”

Today, the availability of alcohol in liquid form, without the gut-filling pulp of fermenting fruit, means it’s easy to overindulge. The idea that humans’ natural affinity for alcohol is inherited from our primate ancestors could help society deal with the adverse consequences of alcohol abuse.

“Excessive consumption of alcohol, as with diabetes and obesity, can then be viewed conceptually as a disease of nutritional excess,” Campbell said.

Korber, Fischer, Yoon and Theiler are members of a rarified team that the National Institute of Allergy and Infectious Diseases assembled in January 2021, drawing on experts from around the world who specialize in relevant research fields such as viruses, the immune system, vaccines, epidemiology, structural biology, bioinformatics, virus genetics, and evolution. The team is called SAVE, for SARS-CoV-2 Assessment of Viral Evolution.

As noted in the Nature paper, the authors state, “This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting transmission, virulence, and resistance to convalescent and vaccine-induced immunity. The SAVE program serves as a critical data-generating component of the United States Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines and therapeutics and for communicating public health risk.”

Broad model for rapid response

SAVE focuses on mutations in SARS-CoV-2 and emerging virus variants. But its members say the global collaborative concept “is a broad model for rapidly responding to evolving pathogens with pandemic potential.”

“Over the past two decades, we have witnessed the emergence/re-emergence of several RNA viruses, including West Nile virus, H1N1 influenza virus, chikungunya virus, Zika virus, SARS-CoV-1, MERS-CoV and Ebola virus, that have threatened global public health,” the paper’s summary states. “Developing collaborative programs between academic, industry and commercial partners is essential to respond to rapidly evolving viruses,” said Marciela DeGrace of NIAID, the paper’s lead author.

SAVE members represent 58 different research sites located in the United States and around the world. Members participate within three sub-groups:

• Early Detection and Analysis
• In Vitro — what they can learn using flasks, beakers and tubes
• In Vivo — what they can learn in animal models that mimic human disease

Early detection methods

Korber’s team was part of the Early Detection and Analysis team, where such high-impact work as the initial identification of mutations in the virus made waves in the scientific community before its capacity for mutation had been clearly understood and accepted.

The Nature paper notes, “The process is collaborative and iterative, with seven teams using independent models and methodologies to prioritize mutations and lineages as well as rank importance for downstream testing. While the focus is on human infections, the Early Detection group also monitors variants circulating in animal populations, such as mink and deer, since they represent a potential reservoir source.”

On a weekly basis, the SAVE Early Detection and Analysis team reviews downloads of SARS-CoV-2 genomes from the international initiative for sequence sharing, GISAID. They search for variant and co-variant signatures in the genomes, then divide the work into two approaches:

• one based on convergent evolution as the main signal for selection and functional impact of mutations (done byCambridge and Walter Reed Army Institute of Research teams)
• the other anchored on prevalence and growth patterns of mutations and defined lineages (the role ofLos Alamos, Icahn School of Medicine at Mount Sinai, J. Craig Venter Institute/Bacterial Viral Bioinformatic Resource Center, UC-Riverside and Broad Institute teams)

Highlights of Los Alamos impact

At Los Alamos, the Korber team identifies emergent mutational patterns within the SARS-CoV-2 spike protein to track newly emerging and expanding variants and determine transitions in global and regional sampling frequencies over time, which is the specialty area in which Los Alamos has made a huge impact.

They pay particular attention to mutations in parts of the spike protein known to be highly targeted by antibodies, or that might impact infectivity. They also systematically define the most commonly circulating form of each emerging variant of interest or concern against the backdrop of the continuously evolving virus.

“Identifying the emerging variants, and obtaining accurate sequences for those variants, required continued wrangling of burgeoning data,” said Theiler. “There are now close to 10 million SARS-CoV-2 sequences in GISAID. These sequences, however, are non-uniformly sampled, are often partial and some contain errors, and of course it is the newest variants that give the sequencers the most trouble.”

“The tools we developed, along with our colleagues on the LANL COVID-19 Viral Genome Analysis Pipeline (cov.lanl.gov), provided the infrastructure that enabled us to follow this pandemic though its various waves,” he added.

Korber noted that “by working with the SAVE Early Detection team, we were able to be part of a synergistic collaborative effort, where our results in terms of early detection could be cross-checked with those of others.”

She added, “The real beauty of being part of the larger SAVE project was the knowledge that our analysis pipeline could provide foundational support for the many experimental teams in SAVE, and that we could help the scientific community get the best version of newly emergent variants into their laboratories as quickly and accurately as possible. In this way the science needed to understand the immunological and virological characteristics of new variants was rapidly obtained, in time to help inform public health decisions.”

The findings, which are reported in the journal Science Advances, are based on an analysis of more than 630 billion words drawn from internet web pages, using artificial intelligence tools to measure what words mean based on how they are used by millions of individuals.

“Many forms of bias, such as the tendency to associate ‘science’ with men more than women, have been studied in the past, but there has been much less work on how we view a ‘person,’ ” says April Bailey, a postdoctoral researcher in New York University’s Department of Psychology and the lead author of the paper.

“Our findings show that even when using gender-neutral terms, we prioritize men over women,” adds co-author Adina Williams, a research scientist at Meta AI and a graduate of NYU’s doctoral program in linguistics.

Bias at such a foundational level — our word choices — is potentially consequential, the researchers note.

“Conceptions of ‘people’ form the basis of many societal decisions and policymaking,” observes Andrei Cimpian, a professor in New York University’s Department of Psychology and the senior author of the paper. “Because men and women are each about half of the species, prioritizing men in our collective idea of a ‘person’ creates inequity for women in decisions based on this idea.”

The research team examined words’ meanings by considering how they are used by individuals. Specifically, the team studied how we use words expressing the concept of “person” and its gender-specific counterparts, “woman” and “man.”

To test whether we’re likely to think of men more often than we are of women when writing about “people,” the team used artificial intelligence algorithms that learn the meaning of words based on how they are used, drawing from a language repository collected by the non-profit Common Crawl in May 2017. This repository included more than 630 billion mostly English-language words appearing on nearly three billion web pages.

The researchers considered how word meaning is related to word context and use. For example, if you hear, “Each morning, Joe boiled water in the balak for tea,” you might guess that “balak” means something similar to “kettle,” even though “balak” is unfamiliar, because the words alongside “balak” (“tea,” “boiled,” and “water”) also frequently co-occur with “kettle.”

In the Science Advances paper, the researchers investigated, in three studies, the meaning of “person” and related words (e.g., “people”) by taking into account adjacent words — the linguistic context.

In the first study, they compared the similarity in meaning (inferred via linguistic context) between words for people (e.g., “individual”) and words for men (e.g., “he” and “male”) to the similarity in meaning between words for people and words for women (e.g., “she” and “female”).

They found that words for people were used more similarly, and were thus more similar in their meaning, to words for men than to words for women — and by a statistically significant margin. Put another way, the collective concept “people” overlapped more with the concept “men” than with the concept “women” in the studied words.

In the second study, instead of focusing on words for people, the team examined words denoting features central to this concept — specifically, words for traits that commonly describe what people are like. They compared hundreds of trait words identified in past research as common descriptors of people (e.g., “extroverted,” “analytical,” and “superstitious”) to the same lists of words for women and for men from the paper’s initial study.

They found that the meaning of these descriptor words in the second study were, overall, more similar to the meaning of words for men than to the meaning of words for women, with a statistically significant difference between the two. That is, common words that describe what people are like (e.g., “extroverted”) are also used more similarly to words for men than to words for women.

In a third study, the researchers studied the use of verbs — a reasonable area for exploration given the initial findings. Specifically, if the collective concept “people” overlaps more with the concept “men” than with the concept “women,” then words that describe what people do and what is done to them (e.g., “love,” “annoy”) may also be more likely to be similar in their contextual meaning to words denoting men than to words denoting women.

In this study, they compared the meaning similarities between more than 250 verbs that describe actions that people take (e.g., “facilitate,” “smile,” and “threaten”) and words for men vs. words for women.

As with the second study, which focused on common words that describe what people are like, words that describe what people do (e.g., “run”) were also used more similarly to words for men than to words for women — a difference that was again statistically significant.