Culture

WASHINGTON -- A growing number of applications, including smartphone cameras, depend on microlenses to boost performance. A newly developed technology, called laser catapulting, could make it much easier and less expensive to fabricate these miniaturized lenses with customized properties, such as shape or focusing power.

In The Optical Society (OSA) journal Optical Materials Express, researchers from Istituto Italiano di Tecnologia in Italy describe their new laser-additive method for creating microlenses using a single laser pulse. The technology even allows microlenses and microlens arrays to be fabricated directly on cameras or solar cells.

Microlenses improve the performance of cameras and solar cells by concentrating light into the most sensitive areas of the devices. For example, they are widely used in the newest smartphone cameras to increase sensitivity and imaging speed in low-light conditions.

"Our fabrication approach simplifies the production of lenses while allowing more variety in the design and more flexibility in the environments where microlenses can be used," said research team leader Martí Duocastella. "In addition to completely new applications, this method could lead to new cameras that acquire video under low light conditions, solar cells with improved efficiency and microscopes that are better at capturing fast processes."

Catapulting with light

Although micro-optics are commercially available, they can be prohibitively expensive and hard to add to existing devices. Even with traditional microlens fabrication methods such as photolithography, it is difficult to integrate lenses or to make very densely packed microlens arrays.

The researchers developed catapulting to overcome these limitations. The method uses a laser pulse to remove and catapult a micro disk from a thin polymeric film and drop it onto a defined region of interest. The polymer in the microdisk is then heated so it can thermally reflow, allowing capillary forces -- the same ones that make water droplets spherical -- to shape the microdisk into a round lens. Changing the shape of the laser beam allows fabrication of microlenses with different focusing properties or shapes, such as rectangular, triangular or circular.

"Laser catapulting connects the dots between existing laser-based fabrication methods to solve problems with current microlens fabrication strategies," said Duocastella. "It fills the gap between the growing number of applications that require microlenses and the technologies capable of generating on-demand customized micro-optics."

After studying the relationship between the laser beam shape and the resulting microdisks, the researchers explored the reproducibility, precision and accuracy of their technique. Their analysis showed that the method could be used to reproducibly produce microlenses with radiuses between 50 and 250 microns and very high smoothness. Measuring the optical properties of the microlenses and the light collection capabilities of microlens arrays made with the technique showed that these micro-optics exhibited diffraction-limited performance, meaning that they were as good as theory allows.

The researchers say that laser catapulting could be combined with fast laser beam shaping methods for on-the-fly control of optical performance and shape of individual microlenses within an array.

Capturing fast biological processes

The researchers plan to use laser catapulting to fabricate microlenses on top of photodetector arrays so they can develop a high-speed 3D microscopy system to characterize very fast biological processes, such as neuronal communications or virus trafficking. The microlenses will increase the light-collecting efficiency of the photodetectors and thus decrease imaging time.

"These novel photodetector arrays offer important advantages compared to confocal microscopy but can't collect as much light as traditional single point detectors," said Duocastella. "We believe that microlenses, and laser catapulting in particular, will help improve the performance of these photodetector arrays and expand their use among the microscopy community."

A new study has found a high incidence of headaches in pediatric stroke survivors and identified a possible association between post-stroke headache and stroke recurrence. Headache developed in over a third of participating children, on average six months after the stroke. Fifteen percent of patients suffered another stroke, typically in the first six to 12 months after the initial stroke. In the study, most children who experienced headache during stroke recurrence also had other associated neurologic symptoms, mostly weakness of one side of the body (hemiparesis) or facial asymmetry and brain malfunction (encephalopathy). Findings were published in Neurology: Clinical Practice, a journal of the American Academy of Neurology.

"In our study, post-stroke headache was more common in patients who experienced another stroke, which suggests that it might be a risk factor for stroke recurrence," says co-lead author Jonathan Kurz, MD, PhD, pediatric neurologist in the Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program at Ann & Robert H. Lurie Children's Hospital of Chicago, and Instructor of Pediatrics at Northwestern University Feinberg School of Medicine. "More research is needed to test this hypothesis, and it remains unclear if headache treatment would lower the risk for stroke recurrence. Children with post-stroke headache might need closer observation or different strategies to prevent another stroke. This requires more study."

The risk of stroke from birth through age 19 years is about five per 100,000 children, according to the Children's Hemiplegia and Stroke Association (CHASA). In children, the risk of stroke is highest in the first year of life, especially during the perinatal period (a few weeks before and after birth).

The study included 115 children, aged 30 days to 18 years, who had survived a stroke. Thirty-six percent of these children experienced headache that occurred more than 30 days after their stroke. Children with post-stroke headache tended to be survivors of a stroke caused by artery disease (arteriopathy). Of these children, over half had headache severe enough to go to the emergency department, and 81 percent were admitted to the hospital for headache.

"Earlier recognition post-stroke headache in children may improve the care, recovery and quality of life in pediatric stroke survivors," says Dr. Kurz. "Further research will help us better understand the causes of post-stroke headache and its association with stroke recurrence."

Cold Spring Harbor, NY -- Noroviruses are a leading cause of food-borne illness outbreaks, accounting for 58% of all outbreaks and cause 685 million cases worldwide each year. There is no effective therapeutic against them. Having knowledge of the intricate structure of the outer layer of noroviruses, the capsid, which allows the virus to attach to its human host, could help in vaccine development.

In vaccines, specific antibodies recognize the capsids and bind to them so they can no longer interact with human cells. "We need to understand what the norovirus capsid shapes actually look like, and the shape differences between different strains," said James Jung, a postdoctoral fellow in Dr. Leemor Joshua-Tor's lab at Cold Spring Harbor Laboratory (CSHL).

Jung and Joshua-Tor led a team to solve the high-resolution structures of four different strains of noroviruses using a cryo-electron microscope. This allowed them to see the intricate architecture of virus shells in high-definition. Their findings are published in the journal PNAS.

Jung gleaned new insights that could help in guiding the development of therapeutics to fight norovirus infection. "Previously, it was thought that the norovirus shells exist in single-sized assemblies consisting of 180 building blocks and 90 surface spikes. What we found was an unexpected mixture of different shell sizes and shapes. We found a smaller form, which consists of just 60 building blocks with 30 surface spikes placed further apart. We also found larger shells made out of 240 building blocks with 120 surface spikes that are lifted significantly above the base of the shell and form a two-layered architecture that could interact differently with the human cells," he said.

The spikes on the shell interact with the host. Jung found that the distance and orientation of the spikes varied across the different strains of noroviruses. "That means each strain will interact differently with human cells," Jung explained. "The way the antibodies bind is also going to be different. Vaccines should be formulated to take into account the variations across strains and structural forms."

A familiar ingredient has been hiding in plain sight on the surface of Jupiter's moon Europa. Using a visible light spectral analysis, planetary scientists at Caltech and the Jet Propulsion Laboratory, which Caltech manages for NASA, have discovered that the yellow color visible on portions of the surface of Europa is actually sodium chloride, a compound known on Earth as table salt, which is also the principal component of sea salt.

The discovery suggests that the salty subsurface ocean of Europa may chemically resemble Earth's oceans more than previously thought, challenging decades of supposition about the composition of those waters and making them potentially a lot more interesting for study. The finding was published in Science Advances on June 12.

Flybys from the Voyager and Galileo spacecrafts have led scientists to conclude that Europa is covered by a layer of salty liquid water encased by an icy shell. Galileo carried an infrared spectrometer, an instrument scientists use to examine the composition of the surface they're examining. Galileo's spectrometer found water ice and a substance that appeared to be magnesium sulfate salts--like Epsom salts, which are used in soaking baths. Since the icy shell is geologically young and features abundant evidence of past geologic activity, it was suspected that whatever salts exist on the surface may derive from the ocean below. As such, scientists have long suspected an ocean composition rich in sulfate salts.

That all changed when new, higher spectral resolution data from the W. M. Keck Observatory on Maunakea suggested that the scientists weren't actually seeing magnesium sulfates on Europa. Most of the sulfate salts considered previously actually possess distinct absorptions that should have been visible in the higher-quality Keck data. However, the spectra of regions expected to reflect the internal composition lacked any of the characteristic sulfate absorptions.

"We thought that we might be seeing sodium chlorides, but they are essentially featureless in an infrared spectrum," says Mike Brown, the Richard and Barbara Rosenberg Professor of Planetary Astronomy at Caltech and co-author of the Science Advances paper.

However, Kevin Hand at JPL had irradiated ocean salts in a laboratory under Europa-like conditions and found that several new and distinct features arise after irradiation, but in the visible portion of the spectrum. He found that the salts changed colors to the point that they could be identified with an analysis of the visible spectrum. Sodium chloride, for example, turned a shade of yellow similar to that visible in a geologically young area of Europa known as Tara Regio.

"Sodium chloride is a bit like invisible ink on Europa's surface. Before irradiation, you can't tell it's there, but after irradiation, the color jumps right out at you," says Hand, scientist at JPL and co-author of the Science Advances paper.

"No one has taken visible wavelength spectra of Europa before that had this sort of spatial and spectral resolution. The Galileo spacecraft didn't have a visible spectrometer. It just had a near-infrared spectrometer," says Caltech graduate student Samantha Trumbo, the lead author of the paper.

"People have traditionally assumed that all of the interesting spectroscopy is in the infrared on planetary surfaces, because that's where most of the molecules that scientists are looking for have their fundamental features," Brown says.

By taking a close look with the Hubble Space Telescope, Brown and Trumbo were able to identify a distinct absorption in the visible spectrum at 450 nanometers, which matched the irradiated salt precisely, confirming that the yellow color of Tara Regio reflected the presence of irradiated sodium chloride on the surface.

"We've had the capacity to do this analysis with the Hubble Space Telescope for the past 20 years," Brown says. "It's just that nobody thought to look."

While the finding does not guarantee that this sodium chloride is derived from the subsurface ocean (this could, in fact, simply be evidence of different types of materials stratified in the moon's icy shell), the study's authors propose that it warrants a reevaluation of the geochemistry of Europa.

"Magnesium sulfate would simply have leached into the ocean from rocks on the ocean floor, but sodium chloride may indicate that the ocean floor is hydrothermally active," Trumbo says. "That would mean Europa is a more geologically interesting planetary body than previously believed."

Supersized alcopops are ready-to-drink flavored alcoholic beverages with high alcohol content. Drinking just one of the 23.5 oz. cans constitutes binge drinking. Drinking multiple cans can lead to alcohol poisoning and death. Four Loko is the leading brand of supersized alcopop consumed by underage drinkers. A new study led by George Mason University's College of Health and Human Services (CHHS) found that Four Loko is among the cheapest ready-to-drink alcoholic beverages available in the United States. Due to the link between lower alcohol prices and higher consumption and related harms, particularly among youth, this is a public health concern.

CHHS Assistant Professor Dr. Matthew Rossheim led the study that examined Four Loko's retail price in large U.S. cities. CHHS students in the Department of Global and Community Health Kayla McDonald, Reema Ahmad, and Sieka Siklo were co-authors. The study was published in Alcoholism: Clinical and Experimental Research.

These supersized alcopops are popular among underage youth, and a single 23.5 oz. can contains about three times the alcohol content of a regular beer. Moreover, they are sold in containers twice as large, so they have the alcohol content of a six-pack of beer and retail for less than $3. According to the researchers, it is urgently important that the high alcohol-by-volume (abv) in these products be reduced, they are banned altogether, or their price is increased, so that young people can't obtain a lethal dose of sugar-sweetened alcohol for $10.

"It is unsafe for anyone to consume a single can of Four Loko in one sitting, let alone minors who have less drinking experience and lower body weight," cautions Rossheim. "Regulatory agencies should reduce the availability and alcohol-by-volume of these products and increase their retail price in order to reduce and prevent unsafe alcohol consumption."

This study collected data from a random sample of stores in the largest city of each state and in Washington, D.C. Retailers were interviewed about Four Loko availability, volume, abv, price for one can, and discounts for buying more than one can.

The manufacturer of Four Loko has ignored requests from 17 State Attorneys General to reduce the high alcohol content of these products. To the contrary, they have recently introduced even higher abv products.

The researchers recommend passing legislation that improves regulation on Four Loko and other supersized alcopops. This would include increasing their price, removing them from the types of stores that underage youth have access to (e.g., gas stations and convenience stores), and launching an investigation from the Alcohol and Tobacco Tax and Trade Bureau on whether these products meet the federal definition for beer or manufacturers are evading federal and state taxes.

This summer, Rossheim will also be leading eye-tracking research to examine alcohol product packaging's appeal to youth.

A mite that spreads a dangerous virus among honeybees also plays an indirect role in infecting wild bumblebees, new research shows.

The Varroa destructor mite lives on honeybees and can spread deformed wing virus (DWV) throughout the hive.

The mite has emerged as a parasite of Western honeybees, after switching from its original host, the Asian honeybee at the beginning of the last century. It has since spread globally through the man-made movement of infested honeybee hives and has turned into a viral vector.

The invasive mite does not live on bumblebees, but University of Exeter scientists have discovered it indirectly affects them by raising infection rates among honeybees, which then spread DWV to nearby bumblebees.

The researchers say their findings highlight the need for beekeepers to treat honeybee colonies affected by mites in order to protect wild bees.

"We compared areas where honeybees had Varroa destructor mites with mite-free areas," said Dr Robyn Manley, of the Centre for Ecology and Conservation on the University of Exeter's Penryn Campus in Cornwall.

"In areas where mites were present - and therefore spreading DWV among honeybees - we found higher rates of the virus among wild bumblebees. Infected honeybees share their environment with bumblebees, feeding on the same flowers and passing on the virus. In effect, the mites turn honeybees into 'super spreaders' of DWV."

A large proportion of honeybees in Britain and many other countries live in hives kept by beekeepers, and Dr Manley said the study raised an important point for them. "Some beekeepers prefer not to intervene if mites appear in their colonies, but this could be endangering wild bees," she said.

As parasites on honeybee pupae and adults, Varroa destructor mites spread DWV - which is associated with dramatic colony losses due to increased over-winter mortality.

"There is a global epidemic of DWV, partly driven by the spread of the Varroa destructor mite," said Professor Wilfert, of the University of Ulm, Germany.

"We know the virus severely affects honeybee colonies. There has been less research into the impact on wild bumblebees, but studies so far suggest it can reduce their lifespan. These results emphasise the important role of beekeepers, regulators and landscape managers in maintaining the health of both managed honeybees and wild bee populations."

There are various strains of DWV, and the Exeter study supports the view that DWV-B is taking over from DWV-A as the most prevalent strain. DWV-B is known to be more harmful to honeybees, but it is not yet clear if and how the strains affect wild bumblebees differently.

A chemical residue study of incense burners from ancient burials at high elevations in the Pamir Mountains of western China has revealed psychoactive cannabinoids.

This study, conducted by researchers from the University of the Chinese Academy of Sciences, Chinese Academy of Social Sciences and the Max Planck Institute for the Science of Human History, provides some of the earliest clear evidence for the use of cannabis for its psychoactive compounds, and the awareness of higher tetrahydrocannabinol (THC)-producing varieties of the plant.

Cannabis plants were cultivated in East Asia for their oily seeds and fiber from at least 4000 BC. Little is known, however, about the early use and eventual cultivation of the plant for its psychoactive and medicinal properties. Despite being one of the most widely used psychoactive drugs in the world today, there is little archaeological or historical evidence for the use of marijuana in the ancient world.

Researchers have identified psychoactive compounds preserved in 2500-year-old funerary incense burners (braziers) from the Jirzankal Cemetery in the eastern Pamirs, China, showing that people were selecting plants with higher levels of THC and burning them as part of mortuary rituals.

This is the earliest clear evidence so far of cannabis being used for its psychoactive properties. The study was recently published in the journal Science Advances.

The researchers used gas chromatography-mass spectrometry to isolate and identify compounds preserved in the ancient wooden braziers discovered by archaeologists from the Chinese Academy of Social Sciences who were excavating in the high mountainous regions of western China.

The braziers were recovered from 2500-year-old tombs discovered in the Pamir Mountains. The chemical signature of the isolated compounds exactly matched the chemical signature of cannabis.

Moreover, the signature indicated a higher level of THC than is normally found in wild cannabis plants. The data produced by the research effort, which brought together archaeologists and laboratory scientists from Beijing, China and Jena, Germany, provide clear evidence that ancient people in the Pamir Mountains burned specific varieties of cannabis that had higher THC levels.

The findings corroborate other early evidence of cannabis from burials further north, in the Xinjiang region of China and in the Altai Mountains of Russia.

"The findings support the idea that cannabis plants were first used for their psychoactive compounds in the mountainous regions of eastern Central Asia, thereafter spreading to other regions of the world," said Nicole Boivin, director of the Department of Archaeology at the Max Planck Institute for the Science of Human History.

The study suggests that cannabis was likely spread across trade routes along the early Silk Road.

"The exchange routes of the early Silk Road functioned more like the spokes of a wagon wheel than a long-distance road, placing Central Asia at the heart of the ancient world. Our study implies that knowledge of cannabis smoking and specific high chemical-producing varieties of the cannabis plant were among the cultural traditions that spread along these exchange routes," said Robert Spengler, the lead archaeobotanist for the study, also at the Max Planck Institute for the Science of Human History.

The study also suggests that people may have sought and later cultivated more psychoactive varieties of cannabis for use in burial rituals.

Prof. YANG Yimin, the lead analyst for the study at the University of the Chinese Academy of Sciences said, "This study of ancient cannabis use helps us understand early human cultural practices, and speaks to the intuitive human awareness of natural phytochemicals in plants."

YANG has been working on ancient organic residues in East Asia for over ten years. "Biomarker analyses open a unique window onto details of ancient plant exploitation and cultural communication that other archaeological methods cannot offer," he said.

June 12, 2019 -- Alcohol use among Tanzanian youth is rising and the high density of alcohol selling outlets and alcohol advertisements coupled with low enforcement of minimum drinking age laws are likely facilitating this uptick, according to a study by the Columbia University Mailman School of Public Health and Muhimbili University of Health and Allied Sciences. The volume of alcohol advertising that youth encounter in Tanzania is increasing as competition among global and local alcohol producers intensifies. Results of a new study that sought to map the influence of the alcohol environment on adolescent drinking in Tanzania are published in the journal Health and Place.

"The high density of alcohol-selling venues in the areas we investigated makes alcohol readily available to youth," said Marni Sommer, DrPH, RN, associate professor of Sociomedical Sciences at Columbia Mailman School, and senior author

Based on earlier data from cities in northern Tanzania, a majority of youth - 64 percent--can easily purchase alcohol. Among secondary school students, 37 percent reported seeing alcohol advertisements almost daily in the last 30 days.

The two-year study of the structural and environmental context of adolescent alcohol use and alcohol-related risky sexual behavior in urban Tanzania involved weeks of participatory activities with adolescents, in-depth interviews with adolescents and adults, and the mapping of alcohol outlets and advertising which revealed a high density of alcohol-selling outlets around most of the study sites. Density was particularly high around schools and youth centers in the lower income communities.

Participants viewed the number of alcohol outlets in their communities as problematic and recommended limiting the number of alcohol sellers within a given area. "Many adolescents described how constantly seeing alcohol as they go about their daily activities serves as a form of temptation, reminding them of the availability of alcohol and their easy access to it," said Mobolaji Ibitoye, MPH, doctoral candidate in Sociomedical Sciences, and first author.

Specifically, the youth recommended that alcohol not be sold near schools and in residential areas as their presence in such settings increased the temptation to drink; others recommended better enforcement of minimum drinking age laws to prohibit alcohol use among youth under 18 years of age.

Many study participants also endorsed the use of economic policies including taxation to reduce adolescents' access to alcohol. "Participants believed that affordability was a key driver of adolescent alcohol use," noted Ibitoye.

Strong national efforts that regulate all forms of alcohol advertising and marketing in Tanzania will counter aggressive marketing campaigns that target adolescents and normalize drinking, noted the researchers. "We also urge that more research be conducted on the effect of other forms of alcohol promotion on adolescents, such as through social media and promotional concerts," said Sommer.

Given that influencing alcohol outlet density and advertising are often beyond the control of consumers, the World Health Organization has recommended the use of structural interventions to reduce alcohol uptake and use. "Our study participants concur that instead of focusing on individual behaviors and consumption patterns, community zoning to restrict the number of alcohol-selling outlets per area have the potential to reduce alcohol use among adolescents in Tanzania," commented Sommer.

"This study brought to light important insights by showing, from the adolescents' perspective, the effect that environmental alcohol cues have on their drinking or intentions to drink," observed Ibitoye."Our findings underscore the urgency for a comprehensive alcohol policy that addresses availability, advertising and pricing of alcoholic beverages - as well as regulations that are enforced - in order to help create an environment that constrains adolescent alcohol use on a population level."

NEW YORK, NY --A new discovery by researchers at Columbia University Vagelos College of Physicians and Surgeons could fix one of the major shortcomings of current gene-editing tools, including CRISPR, and offer a powerful new approach for genetic engineering and gene therapy.

Their new technology, called INTEGRATE, harnesses bacterial jumping genes to reliably insert any DNA sequence into the genome without cutting DNA. Current gene-editing tools rely on cutting DNA, but those cuts can lead to errors.

"Current tools are like molecular scissors: they cut DNA, but the actual editing is performed by the cell's own DNA repair machinery," says Sam Sternberg, PhD, assistant professor of biochemistry and molecular biophysics at Columbia and senior author of the new study. "You're at the mercy of the cell to finish the job."

The new INTEGRATE technology, published online today in the journal Nature, functions more like molecular glue than molecular scissors.

"Rather than introduce DNA breaks and rely on the cell to repair the break, INTEGRATE directly inserts a user-defined DNA sequence at a precise location in the genome, a capability that molecular biologists have sought for decades," says Sternberg, who was recently recruited to Columbia from Jennifer Doudna's laboratory at UC Berkeley.

Current tools are finicky

Editing a cell's genome with current tools is like using a word processor to edit a huge document, but with software that has a mind of its own. Typically, researchers want to make a small change at one specific sequence of DNA bases, leaving the rest of the genome untouched. The best current tool, built with components from one kind of bacterial CRISPR-Cas system, cuts both strands of the DNA molecule at a specific sequence, like adding a paragraph break to a block of text.

These breaks are only the starting point: the actual 'editing' is performed by the cell's own DNA repair machinery, often using DNA sequences provided by the researcher to fill in the gap.

Relying on the cell's repair machinery has major limitations. Many cells repair the DNA break incorrectly or introduce mistakes in the process, and other cells may not even express the necessary repair machinery to insert new genetic payloads. In addition, DNA breaks trigger a DNA damage response that can have other adverse effects.

This makes gene editing difficult or impossible in some cell types, and severely constrains researchers' ability to introduce precise genetic modifications in a safe manner.

INTEGRATE System Harnesses Jumping Genes

The new work solves that problem with a self-contained DNA editing system - derived from Vibrio cholera bacteria -- that doesn't require any assistance from the cell.

CRISPR is a class of natural defense systems in bacteria that are remarkably diverse. To find new gene-editing tools, Sternberg and three graduate students looked to bacteria to find variations of well-studied CRISPR-Cas systems with unusual properties that would reveal new tool capabilities.

This search led them to a transposon, or "jumping gene," found in the bacterium Vibrio cholerae. This transposon has co-opted the bacterium's CRISPR-Cas system, normally used to thwart mobile genetic elements, to insert itself into different regions of the bacterial genome.

Sternberg and his students found that the transposon integrates into specific sites in the bacterial genome, not by cutting DNA into two, but by using a separate enzyme to slip the transposon into the genome. Importantly, the site where the enzyme, an integrase, inserts the DNA is completely controlled by its associated CRISPR system.

The researchers harnessed this discovery to create a gene-editing tool that can be programed to insert any DNA sequence into any site in a bacterial genome. Like CRISPR, the integrase finds the appropriate site with a guide RNA.

By reprogramming the guide RNA, Sternberg and his students were able to precisely control the location where a piece of donor DNA was integrated. And by replacing the transposon sequence with other DNA payloads, they could insert sequences up to 10,000 bases long into a bacterial genome. Thus, the INTEGRATE technology, unlike other editing tools based on integrases, is the first fully programmable insertion system studied to date.

Sequencing the edited bacteria confirmed that the payloads were inserted precisely, with no extra copies at off-target sites.

Improved Gene Editing

With INTEGRATE, a set of enzymes can carry out the entire DNA integration process, reliably inserting an arbitrary DNA payload into a precise location within a cell's genome, without relying on the host cell's DNA repair machinery.

The technique should enable a vast range of new gene editing opportunities. Many biotechnology products, including gene and cell therapies, engineered crops, and biologics, require precise integration of large genetic payloads.

The INTEGRATE technology offers a fresh new approach with the same programmability and ease of use as CRISPR-Cas9, but without the adverse effects associated with DNA breaks.

"We can program this CRISPR-transposon system to integrate its genetic payload at virtually any genomic site, and by understanding how it works, we will be able to engineer it to be even more effective," says Sternberg.

Next Steps

Sternberg's team developed the INTEGRATE technology using bacterial genetics experiments, and they are now testing it in additional cell types, including mammalian cells.

Based on the developmental trajectory of CRISPR-Cas9 technology, Sternberg says there's good reason to believe that precise DNA integration will work as effectively in mammalian cells as it does in E. coli, opening up the door to basic research uses and eventual clinical applications.

In 2018, researchers at MIT and the auto manufacturer BMW were testing ways in which humans and robots might work in close proximity to assemble car parts. In a replica of a factory floor setting, the team rigged up a robot on rails, designed to deliver parts between work stations. Meanwhile, human workers crossed its path every so often to work at nearby stations.

The robot was programmed to stop momentarily if a person passed by. But the researchers noticed that the robot would often freeze in place, overly cautious, long before a person had crossed its path. If this took place in a real manufacturing setting, such unnecessary pauses could accumulate into significant inefficiencies.

The team traced the problem to a limitation in the robot's trajectory alignment algorithms used by the robot's motion predicting software. While they could reasonably predict where a person was headed, due to the poor time alignment the algorithms couldn't anticipate how long that person spent at any point along their predicted path -- and in this case, how long it would take for a person to stop, then double back and cross the robot's path again.

Now, members of that same MIT team have come up with a solution: an algorithm that accurately aligns partial trajectories in real-time, allowing motion predictors to accurately anticipate the timing of a person's motion. When they applied the new algorithm to the BMW factory floor experiments, they found that, instead of freezing in place, the robot simply rolled on and was safely out of the way by the time the person walked by again.

"This algorithm builds in components that help a robot understand and monitor stops and overlaps in movement, which are a core part of human motion," says Julie Shah, associate professor of aeronautics and astronautics at MIT. "This technique is one of the many way we're working on robots better understanding people."

Shah and her colleagues, including project lead and graduate student Przemyslaw "Pem" Lasota, will present their results this month at the Robotics: Science and Systems conference in Germany.

Clustered up

To enable robots to predict human movements, researchers typically borrow algorithms from music and speech processing. These algorithms are designed to align two complete time series, or sets of related data, such as an audio track of a musical performance and a scrolling video of that piece's musical notation.

Researchers have used similar alignment algorithms to sync up real-time and previously recorded measurements of human motion, to predict where a person will be, say, five seconds from now. But unlike music or speech, human motion can be messy and highly variable. Even for repetitive movements, such as reaching across a table to screw in a bolt, one person may move slightly differently each time.

Existing algorithms typically take in streaming motion data, in the form of dots representing the position of a person over time, and compare the trajectory of those dots to a library of common trajectories for the given scenario. An algorithm maps a trajectory in terms of the relative distance between dots.

But Lasota says algorithms that predict trajectories based on distance alone can get easily confused in certain common situations, such as temporary stops, in which a person pauses before continuing on
their path. While paused, dots representing the person's position can bunch up in the same spot.

"When you look at the data, you have a whole bunch of points clustered together when a person is stopped," Lasota says. "If you're only looking at the distance between points as your alignment metric, that can be confusing, because they're all close together, and you don't have a good idea of which point you have to align to."

The same goes with overlapping trajectories -- instances when a person moves back and forth along a similar path. Lasota says that while a person's current position may line up with a dot on a reference trajectory, existing algorithms can't differentiate between whether that position is part of a trajectory heading away, or coming back along the same path.

"You may have points close together in terms of distance, but in terms of time, a person's position may actually be far from a reference point," Lasota says.

It's all in the timing

As a solution, Lasota and Shah devised a "partial trajectory" algorithm that aligns segments of a person's trajectory in real-time with a library of previously collected reference trajectories. Importantly, the new algorithm aligns trajectories in both distance and timing, and in so doing, is able to accurately anticipate stops and overlaps in a person's path.

"Say you've executed this much of a motion," Lasota explains. "Old techniques will say, 'this is the closest point on this representative trajectory for that motion.' But since you only completed this much of it in a short amount of time, the timing part of the algorithm will say, 'based on the timing, it's unlikely that you're already on your way back, because you just started your motion.'"

The team tested the algorithm on two human motion datasets: one in which a person intermittently crossed a robot's path in a factory setting (these data were obtained from the team's experiments with BMW), and another in which the group previously recorded hand movements of participants reaching across a table to install a bolt that a robot would then secure by brushing sealant on the bolt.

For both datasets, the team's algorithm was able to make better estimates of a person's progress through a trajectory, compared with two commonly used partial trajectory alignment algorithms. Furthermore, the team found that when they integrated the alignment algorithm with their motion predictors, the robot could more accurately anticipate the timing of a person's motion. In the factory floor scenario, for example, they found the robot was less prone to freezing in place, and instead smoothly resumed its task shortly after a person crossed its path.

While the algorithm was evaluated in the context of motion prediction, it can also be used as a preprocessing step for other techniques in the field of human-robot interaction, such as action recognition and gesture detection. Shah says the algorithm will be a key tool in enabling robots to recognize and respond to patterns of human movements and behaviors. Ultimately, this can help humans and robots work together in structured environments, such as factory settings and even, in some cases, the home.

"This technique could apply to any environment where humans exhibit typical patterns of behavior," Shah says. "The key is that the [robotic] system can observe patterns that occur over and over, so that it can learn something about human behavior. This is all in the vein of work of the robot better understand aspects of human motion, to be able to collaborate with us better."

Archaeological remains of coastal occupation in the form of shell middens are commonly found on today's shorelines, and evidence for shellfish as a food source goes back 164,000 years. Within this time frame, sea-levels changed dramatically and shorelines moved on the scale of kilometers. The current study, published in PLOS ONE, reveals that this movement of coastlines impacted the majority of shell middens by causing shells to wash away or to currently be underwater, and thus has skewed our understanding of past coastal subsistence around the world.

Shells as food waste are a common find in archaeological coastal sites of the last 164,000 years - but many may now be hidden from view

In this study, an international team of researchers quantified patterns that were first described by renowned Australian archaeologist and anthropologist Betty Meehan in the 1970s. Meehan described how modern-day coastal foragers of the Australian coast processed most of their shellfish on the direct shoreline to decrease transport weight and only carried some shells that still contained meat further inland to their main habitation site to be processed there. The researchers theorized that if prehistoric people at a particular site used the same strategy, and if sea-levels rose dramatically since that time, archaeologists today would no longer find evidence of large shell middens related to that population. If only a few shells were found close to the habitation site, researchers might assume that the population did not rely heavily on shellfish for subsistence - and this would of course be incorrect.

Using a large cluster of over 3,000 prehistoric shell midden sites on the Farasan Islands in the Arabian Red Sea, the researchers assessed their spatial and temporal patterns in the context of long-term sea-level change. A selection of sites was radiocarbon dated to 7,500 to 4,700 years ago. During this period, the sea-level of the southern Red Sea was still rising as a result of melting glaciers at the end of the last Ice Age. The rise came to a stop around 6,000 years ago and the sea level was slightly higher (2-3 m) than today. This was followed by a gradual drop over ~2,000 years to our current sea levels, excepting the rise of recent decades.

Coastal exploitation of shellfish changed little during this period, and rates of shell accumulation based on radiocarbon dates indicate that 10 times more shells were deposited at the direct shoreline than at 'post-shore' locations, mirroring Meehan's ethnological research. However, despite their larger size, no shore-line sites are preserved that date to before 6,000 years ago, closely following the sea-level change in this region and pointing toward a large number of sites that must have been lost to the sea since the beginning of coastal subsistence.

Usually well preserved at archaeological sites, shells are easily washed away by rising sea levels

"We already knew that coastal sites are in a precarious situation and we often rely on sites along steep cliffs or a few hundred meters inland to study the collection of shellfish dating to before today's sea-levels," explains first author Niklas Hausmann of the Max Planck Institute for the Science of Human History. "Now we know that not only a little bit was left at the beach, but the bulk of the shell material, which really undermines our idea of how much shellfish was eaten at sites even slightly inland."

"With our study, we have shown that a lot more shellfish meat was eaten in times of lower sea-levels than we previously thought, and we have to get away from the simplified 'shell equals shellfish meat' attitude," explains Hausmann.

Shellfish are often over-represented in the assessment of past coastal subsistence due to their hard shells preserving better than plants or even bones. However, the meat they contain is archaeologically invisible and could have been eaten anywhere. This study shows that the potential use of beach-side processing sites connected to habitational areas cannot be discounted, especially when such coastal processing sites may now be under water.

Researchers from Carnegie Mellon University's Mellon College of Science and College of Engineering have developed a semiliquid lithium metal-based anode that represents a new paradigm in battery design. Lithium batteries made using this new electrode type could have a higher capacity and be much safer than typical lithium metal-based batteries that use lithium foil as anode.

The interdisciplinary research team published their findings in the current issue of Joule.

Lithium-based batteries are one of the most common types of rechargeable battery used in modern electronics due to their ability to store high amounts of energy. Traditionally, these batteries are made of combustible liquid electrolytes and two electrodes, an anode and a cathode, which are separated by a membrane. After a battery has been charged and discharged repeatedly, strands of lithium called dendrites can grow on the surface of the electrode. The dendrites can pierce through the membrane that separates the two electrodes. This allows contact between the anode and cathode, which can cause the battery to short circuit and, in the worst case, catch fire.

"Incorporating a metallic lithium anode into lithium-ion batteries has the theoretical potential to create a battery with much more capacity than a battery with a graphite anode," said Krzysztof Matyjaszewski, J.C. Warner University Professor of Natural Sciences in Carnegie Mellon's Department of Chemistry. "But, the most important thing we need to do is make sure that the battery we create is safe."

One proposed solution to the volatile liquid electrolytes used in current batteries is to replace them with solid ceramic electrolytes. These electrolytes are highly conductive, non-combustible and strong enough to resist dendrites. However, researchers have found that the contact between the ceramic electrolyte and a solid lithium anode is insufficient for storing and supplying the amount of power needed for most electronics.

Sipei Li, a doctoral student in Carnegie Mellon's Department of Chemistry, and Han Wang, a doctoral student in Carnegie Mellon's Department of Materials Science and Engineering, were able to surmount this shortcoming by creating a new class of material that can be used as a semiliquid metal anode.

Working with the Mellon College of Science's Matyjaszewski, a leader in polymer chemistry and materials science, and Jay Whitacre, Trustee Professor in Energy in the College of Engineering and director of the Wilton E. Scott Institute for Energy Innovation at Carnegie Mellon, who is renowned for his work in developing new technologies for energy storage and generation, Li and Wang created a dual-conductive polymer/carbon composite matrix that has lithium microparticles evenly distributed throughout. The matrix remains flowable at room temperatures, which allows it to create a sufficient level of contact with the solid electrolyte. By combining the semiliquid metal anode with a garnet-based solid ceramic electrolyte, they were able to cycle the cell at 10 times higher current density than cells with a solid electrolyte and a traditional lithium foil anode. This cell also had a much longer cycle-life than traditional cells.

"This new processing route leads to a lithium metal-based battery anode that is flowable and has very appealing safety and performance compared to ordinary lithium metal. Implementing new material like this could lead to step change in lithium-based rechargeable batteries, and we are working hard to see how this works in a range of battery architectures," said Whitacre.

The researchers believe that their method could have far reaching impacts. For example, it could be used to create high capacity batteries for electric vehicles and specialized batteries for use in wearable devices that require flexible batteries. They also believe that their methods could be extended beyond lithium to other rechargeable battery systems, including sodium metal batteries and potassium metal batteries and might be able to be used in grid-scale energy storage.

Cannabis has been cultivated as an oil-seed and fibre crop for millennia in East Asia. Little is known, however, about the early use and eventual cultivation of the plant for its psychoactive and medicinal properties. Despite being one of the most widely used psychoactive drugs in the world today, there is little archaeological or historical evidence for the use of marijuana in the ancient world. The current study, published in the journal Science Advances, identified psychoactive compounds preserved in 2,500-year-old funerary incense burners from the Jirzankal Cemetery in the eastern Pamirs. Researchers from the Max Planck Institute for the Science of Human History, the Chinese Academy of Sciences, and the Chinese Academy of Social Sciences have shown that people were selecting plants with higher levels of THC, and burning them as part of mortuary rituals. This is the earliest clear evidence to date of cannabis being used for its psychoactive properties.

Cannabis is one of the most infamous plants on the planet today, especially in light of rapidly changing legislation surrounding its legalisation in Europe and America. Despite the popularity of the plant for its psychoactive properties, very little is known about the earliest use or cultivation of cannabis for its mind-altering effects. Cannabis plants were cultivated in East Asia for their oily seeds and fibre from at least 4000 BC. However, the early cultivated varieties of cannabis, as well as most wild populations, have low levels of THC and other cannabinoid compounds with psychoactive properties. Therefore, it has been a long-standing mystery as to when and where specific varieties of the plant with higher levels of these compounds were first recognized and used by humans. Many historians place the origins of cannabis smoking on the ancient Central Asian steppes, but these arguments rely solely on a passage from a single ancient text from the late first millennium BC, written by the Greek historian Herodotus. Archaeologists have thus long sought to identify concrete evidence for cannabis smoking in Eurasia, but to date, there are few reliable, well-identified and properly dated examples of early cannabis use.

The researchers in the current study uncovered the early cannabis use when they sought to identify the function of ancient wooden burners discovered by archaeologists from the Chinese Academy of Social Sciences, who were excavating in the high mountainous regions of eastern China. The burners were recovered from 2500-year-old tombs in the Pamir mountain range. The international research team used a method called gas chromatography-mass spectrometry to isolate and identify compounds preserved in the burners. To their surprise, the chemical signature of the isolated compounds was an exact match to the chemical signature of cannabis. Moreover, the signature indicated a higher level of THC than is normally found in wild cannabis plants.

The data produced by the research effort, which brought together archaeologists and laboratory scientists from Jena, Germany and Beijing, China, provides clear evidence that ancient people in the Pamir Mountains were burning specific varieties of cannabis that had higher THC levels. The findings corroborate other early evidence for cannabis from burials further north, in the Xinjiang region of China and in the Altai Mountains of Russia. As Nicole Boivin, Director at the Max Planck Institute for the Science of Human History notes, "The findings support the idea that cannabis plants were first used for their psychoactive compounds in the mountainous regions of eastern Central Asia, thereafter spreading to other regions of the world."

Cannabis likely spread across exchange routes along the early Silk Road

The THC-containing residues were extracted from burners from a cemetery known as Jirzankal in the remote Pamir Mountains. Some of the skeletons recovered from the site, situated in modern-day western China, have features that resemble those of contemporaneous peoples further west in Central Asia. Objects found in the burials also appear to link this population to peoples further west in the mountain foothills of Inner Asia. Additionally, stable isotope studies on the human bones from the cemetery show that not all of the people buried there grew up locally.

These data fit with the notion that the high-elevation mountain passes of Central and Eastern Asia played a key role in early trans-Eurasian exchange. Indeed, the Pamir region, today so remote, may once have sat astride a key ancient trade route of the early Silk Road. The Silk Road was at certain times in the past the single most important vector for cultural spread in the ancient world. Robert Spengler, the lead archaeobotanist for the study, also at the Max Planck Institute for the Science of Human History, explains, "The exchange routes of the early Silk Road functioned more like the spokes of a wagon wheel than a long-distance road, placing Central Asia at the heart of the ancient world. Our study implies that knowledge of cannabis smoking and specific high-chemical-producing varieties of the cannabis plant were among the cultural traditions that spread along these exchange routes."

People sought and later cultivated more psychoactive varieties of cannabis for use in burial rituals

Compared to cultivated varieties, wild cannabis plants contain lower levels of THC, one of the psychoactive compounds in cannabis. It is still unclear whether the people buried at Jirzankal actively cultivated cannabis or simply sought out higher THC-producing plants. One theory is that cannabis plants will produce greater quantities of active compounds in response to increased UV radiation and other stressors related to growing at higher elevations. So people roaming the high mountainous regions may have discovered more potent wild plants there, and initiated a new kind of use of the plant.

While modern cannabis is used primarily as a recreational drug or for medical applications, cannabis may have been used rather differently in the past. The evidence from Jirzankal suggests that people were burning cannabis at rituals commemorating the dead. They buried their kin in tombs over which they created circular mounds, stone rings and striped patterns using black and white stones.

Whether cannabis also had other uses in society is unclear, though it seems likely that the plant's ability to treat a variety of illnesses and symptoms was recognized early on. Yimin Yang, researcher at the University of the Chinese Academy of Sciences in Beijing observes, "This study of ancient cannabis use helps us understand early human cultural practices, and speaks to the intuitive human awareness of natural phytochemicals in plants." Dr. Yang has studied ancient organic residues in East Asia for over ten years. He notes that "biomarker analyses open a unique window onto details of ancient plant exploitation and cultural communication that other archaeological methods cannot offer."

Professor Boivin points out that "given the modern political climate surrounding the use of cannabis, archaeological studies like this can help us to understand the origins of contemporary cultural practice and belief structures - which, in turn, can inform policy." As Dr. Spengler observes, "Modern perspectives on cannabis vary tremendously cross-culturally, but it is clear that the plant has a long history of human use, medicinally, ritually, and recreationally, over countless millennia."

UMBC's Hua Lu, professor of biological sciences, and colleagues have found new genetic links between a plant's circadian rhythm (essentially, an internal clock) and its ability to fend off diseases and pests. The findings were 10 years in the making and published in Nature Communications this week. The results could eventually lead to plants that are more resistant to disease-causing pathogens and better treatment for human diseases.

"It's quite cool," Lu says, "because, in both plants and animals, people are beginning to study the crosstalk between the circadian clock and the immunity system."

Timing is everything

In response to daily attacks from bacteria, fungi, and other pests, plants have evolved various strategies to protect themselves. Plants may close their stomata--small openings in the waxy coating on their leaves--to prevent entry by some bacteria. They might produce chemicals such as salicylic acid and jasmonic acid to repel bacteria and insects. They also make a large number of proteins that are important for successful defense.

Actions like closing stomata, producing salicylic acid, and more happen on a daily schedule, often peaking at the times when certain pathogens and pests are most likely to be active. The rhythmic nature of plant defense suggests plants are coordinating their internal clock with their defense system to increase the effectiveness of their defensive actions.

In this study, Lu and colleagues found for the first time that LUX, a central gene in the plant circadian clock, is important for regulating the opening and closing of the stomata at specific times of day, and also for activating defense mediated by salicylic acid and jasmonic acid.

In a typical plant, the stomata open during the day, to enable exchange of gases required for photosynthesis. Then they close at night, to prevent water loss. The stomata also close in response to daytime pathogen attacks. They respond minimally to an attack at night, because they're already closed.

However, in plants with a non-functional version of the LUX gene, Lu found that the stomata are open both day and night. During a daytime attack, the stomata stay open wider than normal plants. During a nighttime attack, though, some of the stomata close. This means that plants lacking a functional LUX gene have less control over when their stomata open, allowing more opportunistic pathogens to get in. This distinction indicates that LUX is critical for the timing of the stomata-driven defense response, tying defense to the circadian clock in a new way.

Lu's research also dives into the relationship between the LUX gene and the defense chemicals salicylic acid and jasmonic acid. While it was known that the circadian clock can regulate defense responses, this paper shows that the reverse is also true: "A properly tuned circadian clock is important for defense activation. When defense is activated, it then can feed back to regulate the circadian clock," Lu says.

The research team specifically showed that the presence of LUX is needed for normal jasmonic acid signaling. In turn, jasmonic acid also affects expression of LUX and the circadian clock. This reciprocal regulation between the circadian clock and defense signaling helps plants balance their energy use for normal growth and development and defense responses.

From farms to pharma

Lu is interested in pursuing further research to figure out how timing influences the plant defense system. How does the circadian clock affect multiple aspects of defense responses? What molecules from pathogens and pests interfere with a plant's circadian clock and subsequently limit its ability to protect itself? Better understanding how clock genes control plant defense and how pathogens interact with plant defense systems could benefit agriculture and beyond.

"Pathogens are everywhere all the time. Often the most active form of a pathogen varies during a day. Also, plants could have different defense strategies at different times of day," explains Lu. "So, when is the best time to apply pesticides? That could depend on the pathogen, its infection mode, and the behavior of your crop plants. I think that field tests are needed to figure out the best time to apply chemicals to achieve the most efficacy in preventing infection or the spread of infection."

Less pesticide use overall would reduce runoff of chemicals into waterways and lower costs for farmers. Reduced use of antibiotics could help stem antibiotic resistance, which would benefit humans, too.

Plus, plants aren't the only ones whose immune system activity fluctuates throughout the day. Animal systems also have daily cycles. So, "similar ideas can be applied to the medical field," Lu says.

There are similarities between the ways plants and animals interact with their pathogens and pests at the molecular level. Maybe in the future, your prescription will come with specific timing instructions, or your surgery will be scheduled based on your immune system activity.

Science in action

Lu says all of her research, and this multi-part paper in particular, is driven by her lab members. "It's great to work with this many dedicated people," she says. "Without them, I couldn't do it."

That includes postdoctoral fellow Chong Zhang, who is now employed by the USDA, and current postdoc Min Gao, who are co-first authors on the new paper. Five undergraduate students and a high school student also contributed to this long-term project. Some of the experiments required testing every four hours over a 24-hour period, which meant someone was sleeping on a couch in the lab when they were underway.

Overall, Lu's team members are driven by the potential benefits their work could contribute to society. They are excited by the prospect of improving crop yields to feed a growing population, reducing pollution, or reducing side effects for human medical treatment through improved timing and dosing.

"This field interests me because I can see my work have some practical applications, and I think that's important," Lu says. "That should be every scientist's goal--to use your knowledge in real life."

Intensifying climate change will increase the future risk of violent armed conflict within countries, according to a study published today in the journal Nature. Synthesizing views across experts, the study estimates climate has influenced between 3% and 20% of armed conflict risk over the last century and that the influence will likely increase dramatically.

In a scenario with 4 degrees Celsius of warming (approximately the path we're on if societies do not substantially reduce emissions of heat-trapping gases), the influence of climate on conflicts would increase more than five times, leaping to a 26% chance of a substantial increase in conflict risk, according to the study. Even in a scenario of 2 degrees Celsius of warming beyond preindustrial levels - the stated goal of the Paris Climate Agreement¬ - the influence of climate on conflicts would more than double, rising to a 13% chance.

"Appreciating the role of climate change and its security impacts is important not only for understanding the social costs of our continuing heat-trapping emissions, but for prioritizing responses, which could include aid and cooperation," said Katharine Mach, director of the Stanford Environment Assessment Facility and the study's lead author.

Climate change-driven extreme weather and related disasters can damage economies, lower farming and livestock production and intensify inequality among social groups. These factors, when combined with other drivers of conflict, may increase risks of violence.

"Knowing whether environmental or climatic changes are important for explaining conflict has implications for what we can do to reduce the likelihood of future conflict, as well as for how to make well-informed decisions about how aggressively we should mitigate future climate change," said Marshall Burke, assistant professor of Earth system science and a co-author on the study.

Finding consensus

Researchers disagree intensely as to whether climate plays a role in triggering civil wars and other armed conflicts. To better understand the impact of climate, the analysis involved interviews with and debates among experts in political science, environmental science, economics and other fields who have come to different conclusions on climate's influence on conflict in the past.

The experts, who also served as co-authors on the study, agree that climate has affected organized armed conflict in recent decades. However, they make clear that other factors, such as low socioeconomic development, the strength of government, inequalities in societies, and a recent history of violent conflict have a much heavier impact on conflict within countries.

The researchers don't fully understand how climate affects conflict and under what conditions. The consequences of future climate change will likely be different from historical climate disruptions because societies will be forced to grapple with unprecedented conditions that go beyond known experience and what they may be capable of adapting to.

"Historically, levels of armed conflict over time have been heavily influenced by shocks to, and changes in, international relations among states and in their domestic political systems," said James Fearon, professor of political science and co-author on the study. "It is quite likely that over this century, unprecedented climate change is going to have significant impacts on both, but it is extremely hard to anticipate whether the political changes related to climate change will have big effects on armed conflict in turn. So I think putting nontrivial weight on significant climate effects on conflict is reasonable."

Planning ahead

Reducing conflict risk and preparing for a changing climate can be a win-win approach. The study explains that adaptation strategies, such as crop insurance, post-harvest storage, training services and other measures, can increase food security and diversify economic opportunities, thereby reducing potential climate-conflict linkages. Peacekeeping, conflict mediation and post-conflict aid operations could incorporate climate into their risk reduction strategies by looking at ways climatic hazards may exacerbate violent conflict in the future.

However, the researchers make clear there is a need to increase understanding of these strategies' effectiveness and potential for adverse side effects. For example, food export bans following crop failures can increase instability elsewhere.

"Understanding the multifaceted ways that climate may interact with known drivers of conflict is really critical for putting investments in the right place," Mach said.