Tech

Overflowing rivers can cause enormous damage: Worldwide, the annual damage caused by river floods is estimated at over 100 billion dollars - and it continues to rise. So far it has not been clear how climate change influences the magnitude of river floods. There were no apparent patterns.

Austrian flood expert Prof. Günter Blöschl from TU Wien (Vienna) has led a large international study involving a total of 35 research groups that provides clear evidence that changes in the magnitude of flood events observed in recent decades can be attributed to climate change. However, climate change does not have the same effect on floods everywhere: In northwestern Europe, floods are becoming increasingly severe, in southern and eastern Europe flood magnitudes mostly tend to decrease, although, in small catchments, they may actually increase. The results of the study have now been published in Nature magazine.

Climate change is a crucial factor

"We already knew from our previous research that climate change is shifting the timing of floods within a year", says Günter Blöschl. "But the key question is: Does climate change also control the magnitude of flood events? So far, the available data had not been sufficient to ascertain whether this is the case or not. We have now examined this question in great detail and can say with confidence: Yes, the influence of climate change is clear".

For the study, data from 3,738 flood measurement stations in Europe from 1960 to 2010 were analysed: "For a long time it has been assumed that climate change is having an impact on the magnitude of flood waters because a warmer atmosphere can store more water," explains Günter Blöschl. "However, this is not the only effect, things are more complicated."

In central and north-western Europe, between Iceland and Austria, flood magnitudes are increasing because precipitation is increasing and the soils are becoming wetter. In southern Europe, on the other hand, flood levels are decreasing, as climate change results in declining precipitation and the higher temperatures cause increased evaporation of water in the soil. However, for small rivers, floods may actually increase due to frequent thunderstorms and deforestation. In the more continental climate of Eastern Europe, the magnitudes of floods tend to decrease due to shallower snow packs in winter associated with higher temperatures. "Processes differ across Europe - but the regional patterns all correspond well with predicted climate change impacts," says Blöschl, "This shows us that we are already in the midst of climate change."

Large changes

The magnitude of the changes is remarkable: they range from a decline of 23.1% per decade (relative to the long-term mean) to an increase of 11.4% per decade. If these trends continue into the future, major effects on flood risk can be expected in many regions of Europe.

Günter Blöschl argues for these findings to be included in flood management strategies: "Regardless of the necessary efforts of climate change mitigation, we will see the effects of these changes in the next decades," says Blöschl. "Flood management must adapt to these new realities."

Pancreatic cancer is one of the most insidious forms of the disease, in which an average of only 9% of patients are alive five years after diagnosis. One of the reasons for such a dismal outcome is that pancreatic cancer cells are able to escape from tumors and enter the bloodstream very early in the disease, meaning that by the time the cancer is discovered, it has usually already spread. Paradoxically, pancreatic tumors appear to almost lack blood vessels altogether, which prevents cancer drugs from reaching and killing them and has puzzled scientists and clinicians trying to understand how the disease progresses.

Now, a new study from Harvard's Wyss Institute for Biologically Inspired Engineering, Boston University, and the University of Pennsylvania has finally shed light on this mystery. Using both in vitro and in vivo models of pancreatic cancer and vasculature, it found that the tumor cells invade nearby blood vessels, destroy the endothelial cells that line them, and replace those cells with tumor-lined structures. This process seems to be driven by the interaction between the protein receptor ALK7 and the protein Activin in pancreatic cancer cells, pointing to a possible target for future treatments. The research is published in Science Advances.

"Our study really brings to light the importance of 'rescuing' the vasculature prior to treating pancreatic cancer, because this disease is actively destroying our only route for delivering drugs to metastatic tumors," said co-first author Duc-Huy Nguyen, Ph.D., a postdoctoral associate at Weill Cornell Medicine who performed the research while a graduate student at the University of Pennsylvania. "If we could prevent the cancer's ablation of the surrounding endothelium by developing an inhibitor specific to the ALK7-Activin pathway, we could preserve the existing blood vessels and deliver drugs to patients to shrink down the tumor mass, which it is currently impossible to do."

Catching a killer

Studying the interactions between pancreatic cancer and blood vessels has historically been very difficult, as it would require multiple, invasive tissue biopsies from human cancer patients, and imaging the disease over time in the internal organs of living mouse models is technically very challenging. The researchers took a different approach by using organs-on-chips: clear, flexible, plastic chips about the size of a USB stick containing microfluidic channels embedded in a collagen matrix that can be lined with living cells kept alive via a constant flow of nutrient-rich media.

To replicate a pancreatic cancer tumor, the team seeded one channel with mouse pancreatic cancer cells, and a neighboring channel with human endothelial cells. They observed that after about four days, the pancreatic cancer cells began to invade the collagen matrix toward the blood vessel channel, and eventually wrapped themselves around the channel, spread along its length, and finally invaded it. During the invasion process, the endothelial cells in direct contact with the cancer cells underwent apoptosis (cell death), leading to a blood vessel channel that was composed exclusively of cancer cells. They saw the same pattern when using human pancreatic cancer cells in the organ-on-chip, and in living mouse models of pancreatic cancer, suggesting that this process may also occur in humans.

Identifying the weapon

The researchers suspected that the mechanism by which pancreatic cancer cells ablate endothelial cells had something to do with the TGF-? signaling pathway, a cascade of molecular interactions that has been implicated in multiple types of cancers. They introduced a TGF-? inhibitor into their organ-on-chip cancer model for seven days, and saw that the ablation of endothelial cells was significantly reduced. When pancreatic cancer cells were implanted into mice who were subsequently given the same inhibitor molecule, their tumors displayed a higher density of blood vessels, confirming that the inhibitor also reduced ablation in vivo.

To further hone in on the specific TGF-? receptor(s) driving the ablation process, the team created a co-culture device in which they grew pancreatic cells surrounded by endothelial cells so they could investigate exactly what was happening at the interface between the two cell types. They identified three candidate receptors - ALK4, ALK5, and ALK7 - and genetically deleted the gene coding for each receptor, first in the endothelial cells, then in the pancreatic cancer cells. They found that only by deleting ALK7 from the cancer cells could they significantly reduce ablation of endothelial cells and slowed cancer cell growth.

The ALK7 receptor has two known binding partners, the proteins Activin and Nodal, and when the researchers exposed in vitro cancer cells to compounds that inhibit each partner, only the Activin inhibitor reduced endothelial ablation, suggesting that the interaction between ALK7 and Activin is the major driver of pancreatic cancer's growth and metastasis. This was further confirmed by knocking out ALK7 expression in cancer cells and then implanting them into mice, which resulted in slower-growing in vivo tumors with higher blood vessel density and fewer apoptotic endothelial cells.

"Not only has our study revealed a major insight into pancreatic cancer biology that could be used to drive the development of new treatments, our cancer-on-a-chip platform opens a new door to being able to more carefully study the interactions between blood vessels and other types of cancers, which could be extremely useful in teasing out these important but complex interactions," said co-first author Esak (Isaac) Lee, Ph.D., who was a Postdoctoral Fellow at the Wyss Institute and Boston University when the research was carried out and is now an Assistant Professor at Cornell University.

The team is actively looking into developing their platform to further understand additional cellular interactions in cancer, including between cancer and immune cells, and between cancer and the perivascular cells that surround and support blood vessels.

"This study really demonstrates the power of using 3D and 2D organotypic models to replicate disease states in vitro and identify precise mechanisms, and their superiority over traditional in vitro and in vivo approaches," said corresponding author Chris Chen, M.D., Ph.D., an Associate Faculty Member at the Wyss Institute who is also a Professor of Biomedical Engineering and Director of the Tissue Microfabrication Laboratory at Boston University. "We are really just beginning to scratch the surface, and we're excited to see what other kinds of insights we can uncover with this platform that could lead to new and better treatments."

"This elegant use of organ-on-a-chip technology by Chris Chen and his team provides an entirely new perspective as to why pancreatic cancer is such a malignant form of this disease, as well as potential new molecular targets that may lead to an entirely new class of anti-cancer therapeutics that act by preventing cancer cell colonization of blood vessels rather than targeting angiogenesis, immune cells, or the cancer cells themselves," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS, the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS).

Addis Ababa, Ethiopia (Aug 28) -- Cleveland Museum of Natural History Curator and Case Western Reserve University Adjunct Professor Dr. Yohannes Haile-Selassie and his team of researchers have discovered a "remarkably complete" cranium of a 3.8-million-year-old early human ancestor from the Woranso-Mille paleontological site, located in the Afar region of Ethiopia. Working for the past 15 years at the site, the team discovered the cranium (MRD-VP-1/1), here referred to as "MRD," in February 2016. In the years following their discovery, paleoanthropologists of the project conducted extensive analyses of MRD, while project geologists worked on determining the age and context of the specimen. The results of the team's findings are published online in two papers in the international scientific journal Nature.

The 3.8-million-year-old fossil cranium (MRD) represents a time interval between 4.1 and 3.6 million years ago when early human ancestor fossils are extremely rare, especially outside the Woranso-Mille area. MRD generates new information on the overall craniofacial morphology of Australopithecus anamensis, a species that is widely accepted to have been the ancestor of Lucy's species, Australopithecus afarensis. MRD also shows that Lucy's species and its hypothesized ancestor, A. anamensis, coexisted for approximately 100,000 years, challenging previous assumptions of a linear transition between these two early human ancestors. Haile-Selassie said, "This is a game changer in our understanding of human evolution during the Pliocene."

Discovery of MRD-VP-1/1 ("MRD"):

The Woranso-Mille project has been conducting field research in the central Afar region of Ethiopia since 2004. The project has collected more than 12,600 fossil specimens representing about 85 mammalian species. The fossil collection includes about 230 fossil hominin specimens dating to between >3.8 and ~3.0 million years ago.

The first piece of MRD, the upper jaw, was found by Ali Bereino (a local Afar worker) on February 10, 2016, at a locality known as Miro Dora, Mille District of the Afar Regional State. The specimen was exposed on the surface, and further investigation of the area resulted in the recovery of the rest of the cranium. "I couldn't believe my eyes when I spotted the rest of the cranium. It was a eureka moment and a dream come true," said Haile-Selassie.

Location of the Discovery

MRD was found in the Woranso-Mille Paleontological Project study area located in Zone 1, Mille District of the Afar Regional State of Ethiopia. Miro Dora is the local name of the area where MRD was found. It is about 550 km northeast of the capital, Addis Ababa, and 55 km north of Hadar ("Lucy's" site).

Geology and Age Determination

In a companion paper published in the same issue of Nature, Beverly Saylor of Case Western Reserve University and her colleagues determined the age of the fossil as 3.8 million years by dating minerals in layers of volcanic rocks nearby. They mapped the dated levels to the fossil site using field observations and the chemistry and magnetic properties of rock layers. Saylor and her colleagues combined the field observations with analysis of microscopic biological remains to reconstruct the landscape, vegetation and hydrology where MRD died.

MRD was found in the sandy deposits of a delta where a river entered a lake. The river likely originated in the highlands of the Ethiopian plateau while the lake developed at lower elevations, where rift activity caused the Earth surface to stretch and thin, creating the lowlands of the Afar region. Debris flows and volcanic ejecta occasionally descended into the otherwise quiet lake, which was ultimately buried by basalt lava flows. This kind of volcanic activity and dramatic landscape change is common in rift settings. "Incredible exposures and the volcanic layers that episodically blanketed the land surface and lake floor allowed us to map out this varied landscape and how it changed over time," said Saylor.

Fossil pollen grains and chemical remains of fossil plant and algae that are preserved in the lake and delta sediments provide clues about the ancient environmental conditions. Specifically, they indicate that the lake near where MRD finally rested was likely salty at times and that the watershed of the lake was mostly dry, but that there were also forested areas on the shores of the delta or alongside the river that fed the delta and lake system. "MRD lived near a large lake in a region that was dry. We're eager to conduct more work in these deposits to understand the environment of the MRD specimen, the relationship to climate change and how it affected human evolution, if at all," said Naomi Levin, a co-author on the study from University of Michigan.

Significance of the Discovery

1. Among the most important findings was the team's conclusion that Australopithecus anamensis and its descendant species, the well-known Australopithecus afarensis, coexisted for a period of at least 100,000 years. This finding contradicts the long-held notion of an anagenetic relationship between these two taxa, whereby one species disappears only by giving rise to a new species in a linear fashion.

2. Australopithecus anamensis is the oldest known member of the genus Australopithecus. The species was previously only known through teeth and jaw fragments, all dated to between 4.2 and 3.9 million years ago. The similarities between the preserved dentition of the 3.8-million-year-old MRD and the previously known teeth and jaw fragments of A. anamensis led to a positive identification of MRD as a member of A. anamensis. Additionally, due to the cranium's rare near-complete state, the researchers identified never-before-seen facial features in the species. "MRD has a mix of primitive and derived facial and cranial features that I didn't expect to see on a single individual," Haile-Selassie said. Dr. Stephanie Melillo of the Max Planck Institute for Evolutionary Anthropology in Germany, co-author of the papers, further said, "A. anamensis was already a species that we knew quite a bit about, but this is the first cranium of the species ever discovered. It is good to finally be able to put a face to the name."

Some characteristics were shared with its descendant species, Australopithecus afarensis, while others differed significantly and had more in common with those of even older and more primitive early human ancestor groups, such as Ardipithecus and Sahelanthropus.

3. The distinct differences between the 3.8-million-year-old MRD specimen and a previously unassigned 3.9-million-year-old hominin cranium fragment--commonly known as the Belohdelie frontal and discovered in the Middle Awash of Ethiopia by a team of paleontologists in 1981--also proved significant. The preserved features of the Belohdelie frontal differed from those of MRD but were significantly similar to those of the known cranial specimens of Lucy's species. As a result, the new study confirms that the Belohdelie frontal belonged to an individual of Lucy's species. This identification extends the earliest record of Australopithecus afarensis back to 3.9 million years ago, indicating a period of at least 100,000 years' overlap with its ancestor, Australopithecus anamensis.

4. The 3.8-million-year-old MRD specimen was buried in a river delta on the margin of a lake that formed in an actively rifted landscape with steep hillsides and volcanic eruptions that blanketed the land surface with ash and lava. There were forested areas on the shores of the delta or along the edges of the river that flowed into the delta and lake system, but the watershed that fed the river, delta and lake system was mostly dry with few trees.

OAKLAND, Calif. - Aug. 28, 2019 - Kaiser Permanente has demonstrated promising results in reducing secondary cardiac events and rehospitalizations by creating a virtual cardiac rehabilitation program that fits seamlessly into patients' lives. Increasing rates of program enrollment and completion have been key factors in the improved outcomes. Results and details about the program were published today in NEJM Catalyst.

Cardiovascular disease is the leading cause of death in the United States . While cardiac rehabilitation programs -- prescribed exercise and diet, as well as health education and counseling -- can significantly reduce the risks related to cardiovascular disease, few cardiac patients enroll in rehabilitation programs, and even fewer complete them .

Kaiser Permanente's virtual cardiac rehabilitation program, developed in collaboration with Samsung, combines wearable technology with support from an assigned health care team. The program has enrolled more than 2,300 patients, making Kaiser Permanente's virtual cardiac rehabilitation program one of the largest in the U.S. More than 80% of the patients who have joined the program complete it, compared to the national average of less than 50%. Cardiac-related hospital readmissions for patients in Kaiser Permanente's program have been less than 2%, compared to 10-15% average for most programs .

"Knowing that lifestyle change plays such a critical role in the long-term health of cardiac patients, we set out to find a way to make the rehabilitation program as easy and seamless as possible for our members," said Tad Funahashi, MD, who leads clinical innovation at Kaiser Permanente in Southern California. "By working closely with patients, care providers, and case managers we were able to do just that. Our virtual cardiac rehabilitation program is proving to keep patients engaged and reduce readmissions."

The Kaiser Permanente program has graduated 1,880 patients since 2018. Clinicians anticipate serving the needs of more than 5,000 patients in 2019.

"Weekly contact with the nurse provided tremendous reassurance for me," said Michelle Wofford, 42, a Kaiser Permanente member who enrolled in the program after she had a stent placed to open a blockage in a coronary artery. "In addition to using the watch and smartphone app to stay on track with my physical activity, I also had access to a nutrition class. The Plants for Life class was life-changing and emotional for me because I realized that I needed to change my diet to avoid going down a path I could not come back from."

About the Virtual Cardiac Rehabilitation Program

Patients are encouraged to enroll in the eight-week virtual cardiac rehabilitation program. Once enrolled, patients meet with their care team to create a rehabilitation program specific to their unique needs. They use a Samsung smartwatch that pairs via Bluetooth with an Apple or Android smartphone. The watch sends reminders to the patient to exercise, collects patient activity data and continuously displays the patient heart rate during exercise. This data is automatically uploaded via the smartphone into the patient's chart so that clinicians, case managers and physical therapists can track patient progress and engage with them accordingly.

Using the smartphone and Kaiser Permanente's existing digital platform, patients meet virtually with a care manager once a week to discuss their progress and learn about lifestyle modification as it relates to their own unique needs. They can also contact a care manager for an immediate response to concerns about symptoms or medications. After graduation from the program, wellness coaching is offered for an additional eight to 12 weeks to assist members in their journey toward lifestyle change.

"The clinical benefits of regular meetings with and 24/7 access to the care team are two-fold: Care providers foster stronger relationships with patients due to additional touch-points, and patients receive a more holistic treatment plan with wraparound services such as wellness coaching and counseling," said Columbus Batiste, MD, chief of cardiology at Kaiser Permanente Riverside Medical Center. "However, for many patients, the most rewarding aspect of virtual cardiac rehab was having ownership over their health. By tracking progress, patients became invested in their care."

Menlo Park, Calif. -- Scientists at the Department of Energy's SLAC National Accelerator Laboratory and Stanford University have made the first nickel oxide material that shows clear signs of superconductivity - the ability to transmit electrical current with no loss.

Also known as a nickelate, it's the first in a potential new family of unconventional superconductors that's very similar to the copper oxides, or cuprates, whose discovery in 1986 raised hopes that superconductors could someday operate at close to room temperature and revolutionize electronic devices, power transmission and other technologies. Those similarities have scientists wondering if nickelates could also superconduct at relatively high temperatures.

At the same time, the new material seems different from the cuprates in fundamental ways - for instance, it may not contain a type of magnetism that all the superconducting cuprates have - and this could overturn leading theories of how these unconventional superconductors work. After more than three decades of research, no one has pinned that down.

The experiments were led by Danfeng Li, a postdoctoral researcher with the Stanford Institute for Materials and Energy Sciences at SLAC, and described today in Nature.

"This is a very important discovery that requires us to rethink the details of the electronic structure and possible mechanisms of superconductivity in these materials," said George Sawatzky, a professor of physics and chemistry at the University of British Columbia who was not involved in the study but wrote a commentary that accompanied the paper in Nature. "This is going to cause an awful lot of people to jump into investigating this new class of materials, and all sorts of experimental and theoretical work will be done."

A difficult path

Ever since the cuprate superconductors were discovered, scientists have dreamed of making similar oxide materials based on nickel, which is right next to copper on the periodic table of the elements.

But making nickelates with an atomic structure that's conducive to superconductivity turned out to be unexpectedly hard.

"As far as we know, the nickelate we were trying to make is not stable at the very high temperatures - about 600 degrees Celsius - where these materials are normally grown," Li said. "So we needed to start out with something we can stably grow at high temperatures and then transform it at lower temperatures into the form we wanted."

He started with a perovskite - a material defined by its unique, double-pyramid atomic structure - that contained neodymium, nickel and oxygen. Then he doped the perovskite by adding strontium; this is a common process that adds chemicals to a material to make more of its electrons flow freely.

This stole electrons away from nickel atoms, leaving vacant "holes," and the nickel atoms were not happy about it, Li said. The material was now unstable, making the next step - growing a thin film of it on a surface - really challenging; it took him half a year to get it to work.

'Jenga chemistry'

Once that was done, Li cut the film into tiny pieces, loosely wrapped it in aluminum foil and sealed it in a test tube with a chemical that neatly snatched away a layer of its oxygen atoms - much like removing a stick from a wobbly tower of Jenga blocks. This flipped the film into an entirely new atomic structure - a strontium-doped nickelate.

"Each of these steps had been demonstrated before," Li said, "but not in this combination."

He remembers the exact moment in the laboratory, around 2 a.m., when tests indicated that the doped nickelate might be superconducting. Li was so excited that he stayed up all night, and in the morning co-opted the regular meeting of his research group to show them what he'd found. Soon, many of the group members joined him in a round-the-clock effort to improve and study this material.

Further testing would reveal that the nickelate was indeed superconducting in a temperature range from 9-15 kelvins - incredibly cold, but a first start, with possibilities of higher temperatures ahead.

More work ahead

Research on the new material is in a "very, very early stage, and there's a lot of work ahead," cautioned Harold Hwang, a SIMES investigator, professor at SLAC and Stanford and senior author of the report. "We have just seen the first basic experiments, and now we need to do the whole battery of investigations that are still going on with cuprates."

Among other things, he said, scientists will want to dope the nickelate material in various ways to see how this affects its superconductivity across a range of temperatures, and determine whether other nickelates can become superconducting. Other studies will explore the material's magnetic structure and its relationship to superconductivity.

RIVERSIDE, Calif. -- A team led by a psychiatrist at the University of California, Riverside, has tested the orally administered investigational medication ecopipam on adults who stutter in an open-label, uncontrolled clinical trial and found that it reduced their stuttering symptoms from the start of therapy after eight weeks of dosing.

Positive results included increased speech fluency, faster reading completion, and shortened duration of stuttering events.

"Ecopipam was well tolerated by the study participants," said Dr. Gerald Maguire, chair of psychiatry and neuroscience in the UCR School of Medicine, who led the study published this month in the Annals of Clinical Psychiatry. "They showed no serious adverse effects, no patient stopped treatment due to adverse events, and there were no signals of weight gain or abnormal movement disorders, events that may accompany other medications used to treat stuttering."

Maguire added that ecopipam will now be tested early next year for its efficacy and safety in adult patients who stutter in a larger, randomized, double-blind, placebo-controlled clinical trial conducted by the biopharmaceutical company Emalex Biosciences. More than 100 adults at multiple sites in the United States, including UC Riverside, will participate in the 12-week double-blind portion of the trial, which will be followed by a one-year, open-label extension.

"If ecopipam is found at the end of this trial to be a potentially safe and effective treatment for stuttering, it would be a major step toward seeking FDA approval for the first-ever medication to treat stuttering, a significant development for the millions of people around the world who stutter, bringing them hope and empowerment," said Maguire, chair of the board of directors of the National Stuttering Association, and a person who stutters himself. "It may help them function better in social and academic settings, being able to communicate more freely with a resultant improvement in their quality of life."

"We look forward to building on the research initiated by Dr. Maguire and his colleagues at UC Riverside and to collaborating on future clinical trials of ecopipam in an underserved patient population with limited pharmacologic treatment options," said Timothy Cunniff, a clinical adviser to Emalex Biosciences.

Stuttering, a chronic neurodevelopmental disorder affecting about 3 million Americans, begins most often in childhood. A precise cause of this complex communicative disorder is not known. Affecting four men for every one woman, stuttering is best addressed with early intervention.

The neurotransmitter dopamine plays an important role in how stuttering is caused in the brain. Because high levels of cerebral dopamine levels are associated with stuttering, medications have targeted dopamine to improve stuttering symptoms. But many of these medications have produced movement disorders in patients, as well as metabolic abnormalities -- negative effects not observed with ecopipam in clinical trials conducted to date.

Ecopipam selectively blocks the actions of dopamine at its receptor. Dopamine receptors can be broadly classified into two families based on their structures: D1 receptors and D2 receptors. Ecopipam blocks dopamine only at D1 receptors, and thus may act differently than other commercially available medications.

Nine adult males participated in the eight-week, open-label pilot study conducted at UC Riverside in cooperation with CITrials. Two patients dropped out during the study, one for lack of efficacy and one for noncompliance. Identical twins were excluded from the analysis population due to a suspected genetic trait that causes fast metabolism. Participants began with 50 milligrams per day of ecopipam for two weeks. If they tolerated this dosage, they received 100 milligrams per day of the drug for the remaining six weeks of the trial. Of the five evaluable patients, three participants with moderate stuttering made significant improvements in overall stuttering. The other two participants had severe stuttering and showed modest gains in overall stuttering severity.

Two McGill University astronomers have assembled a "fingerprint" for Earth, which could be used to identify a planet beyond our Solar System capable of supporting life.

McGill Physics student Evelyn Macdonald and her supervisor Prof. Nicolas Cowan used over a decade of observations of Earth's atmosphere taken by the SCISAT satellite to construct a transit spectrum of Earth, a sort of fingerprint for Earth's atmosphere in infrared light, which shows the presence of key molecules in the search for habitable worlds. This includes the simultaneous presence of ozone and methane, which scientists expect to see only when there is an organic source of these compounds on the planet. Such a detection is called a "biosignature".

"A handful of researchers have tried to simulate Earth's transit spectrum, but this is the first empirical infrared transit spectrum of Earth," says Prof. Cowan. "This is what alien astronomers would see if they observed a transit of Earth."

The findings, published Aug. 28 in the journal Monthly Notices of the Royal Astronomical Society, could help scientists determine what kind of signal to look for in their quest to find Earth-like exoplanets (planets orbiting a star other than our Sun). Developed by the Canadian Space Agency, SCISAT was created to help scientists understand the depletion of Earth's ozone layer by studying particles in the atmosphere as sunlight passes through it. In general, astronomers can tell what molecules are found in a planet's atmosphere by looking at how starlight changes as it shines through the atmosphere. Instruments must wait for a planet to pass - or transit - over the star to make this observation. With sensitive enough telescopes, astronomers could potentially identify molecules such as carbon dioxide, oxygen or water vapour that might indicate if a planet is habitable or even inhabited.

Cowan was explaining transit spectroscopy of exoplanets at a group lunch meeting at the McGill Space Institute (MSI) when Prof. Yi Huang, an atmospheric scientist and fellow member of the MSI, noted that the technique was similar to solar occultation studies of Earth's atmosphere, as done by SCISAT.

Since the first discovery of an exoplanet in the 1990s, astronomers have confirmed the existence of 4,000 exoplanets. The holy grail in this relatively new field of astronomy is to find planets that could potentially host life - an Earth 2.0.

A very promising system that might hold such planets, called TRAPPIST-1, will be a target for the upcoming James Webb Space Telescope, set to launch in 2021. Macdonald and Cowan built a simulated signal of what an Earth-like planet's atmosphere would look like through the eyes of this future telescope which is a collaboration between NASA, the Canadian Space Agency and the European Space Agency.

The TRAPPIST-1 system located 40 light years away contains seven planets, three or four of which are in the so-called "habitable zone" where liquid water could exist. The McGill astronomers say this system might be a promising place to search for a signal similar to their Earth fingerprint since the planets are orbiting an M-dwarf star, a type of star which is smaller and colder than our Sun.

"TRAPPIST-1 is a nearby red dwarf star, which makes its planets excellent targets for transit spectroscopy. This is because the star is much smaller than the Sun, so its planets are relatively easy to observe," explains Macdonald. "Also, these planets orbit close to the star, so they transit every few days. Of course, even if one of the planets harbours life, we don't expect its atmosphere to be identical to Earth's since the star is so different from the Sun."

According to their analysis, Macdonald and Cowan affirm that the Webb Telescope will be sensitive enough to detect carbon dioxide and water vapour using its instruments. It may even be able to detect the biosignature of methane and ozone if enough time is spent observing the target planet.

Prof. Cowan and his colleagues at the Montreal-based Institute for Research on Exoplanets are hoping to be some of the first to detect signs of life beyond our home planet. The fingerprint of Earth assembled by Macdonald for her senior undergraduate thesis could tell other astronomers what to look for in this search. She will be starting her Ph.D. in the field of exoplanets at the University of Toronto in the Fall.

Around 1.4 billion fewer cigarettes are being smoked every year according to new research funded by Cancer Research UK, published today in JAMA Network Open*.

Between 2011 and 2018, average monthly cigarette consumption fell by nearly a quarter, equating to around 118 million fewer cigarettes being smoked every month**.

This decline suggests that stricter tobacco laws and taking action to encourage people to quit smoking are working.

The researchers, based at UCL, looked at cigarette sales data for England and compared this with the monthly self-reported cigarette use of over 135,000 individuals from the Smoking Toolkit Study***. They found that the two different methods of looking at how many cigarettes people are smoking provided similar results****.

Over the whole period, the average number of cigarettes smoked monthly declined by 24.4% based on survey data and 24.1% based on sales data from 3.40 billion and 3.41 billion a month to 2.57 billion and 2.58 billion, respectively.

Lead author, Dr Sarah Jackson from UCL's Tobacco and Alcohol Research Group, said: "It's brilliant that over a billion fewer cigarettes are being sold and smoked in England every year. The decline in national cigarette consumption has been dramatic and exceeded the decline in smoking prevalence, which, over the same time period, was around 15%. This means that not only are fewer people smoking, but those who continue to smoke are smoking less.

"Studies like this help to give us an accurate picture of cigarette consumption so we know where we're at and what more needs to be done."

Currently 16% of English adults smoke cigarettes*****.

George Butterworth, senior policy manager at Cancer Research UK, said: "It's great news that fewer cigarettes are being sold and smoked. Big tobacco said that introducing stricter regulation wouldn't work and campaigned against it, but this is proof that smoking trends are heading in the right direction. But smoking is still the biggest preventable cause of cancer, and certain groups have much higher rates of smoking, such as routine and manual workers, so we can't stop here and think job done.

"Last month the government committed to making the UK smokefree by 2030. But stop smoking services, which give smokers the best chance of quitting, have been subject to repeated cuts in recent years. We need the government to fix the funding crisis in local stop smoking services. The tobacco industry could be made to pay for these services to clean up the mess their products have created."

From 9 to 11 September, the [BC]2 Basel Computational Biology Conference, organized by the SIB Swiss Institute of Bioinformatics, will bring together international and Swiss-based scientists working in this field, in one of the key bioinformatics events in Europe: a prime opportunity to hear from leading experts, from precision oncology to infectious diseases.

Why is computational biology key? Technological advances have brought us to the genomic era at full speed, with human sequence data flowing into global repositories at an exponential rate. When combined with the growing wealth of digital health records and clinical trials, these terabytes of data promise invaluable insights into the biological mechanisms of human health, aging and disease. However, without state-of-the-art computational methods, resources and solutions - including machine learning approaches - it is virtually impossible to extract knowledge from them, let alone to derive clinical applications. The [BC]2 Basel Computational Biology Conference precisely aims to foster the transfer of such know-how among today's scientists.

Swiss expertise, international reach. Switzerland has a history of excellence in curation and analysis of biological data thanks to the SIB Swiss Institute of Bioinformatics, created 20 years ago. Every two years, the Institute organizes [BC]2, which this year aims to help filling the gap between Big Data and clinical applications, through a series of workshops and plenary sessions detailing the current status of knowledge. Attracting prestigious keynote speakers and over 300 attendees from around the globe, the conference is deeply rooted in Switzerland, with a scientific committee exclusively composed of Group Leaders of the SIB, including co-chairs Niko Beerenwinkel (ETH Zurich) and Erik van Nimwegen (University of Basel). "The application of Big Data in Medicine holds enormous promise, but by and large these great expectations have yet to be fulfilled. It's a real privilege to be able to gather the world's experts in Switzerland to survey where we stand, and discuss what the key challenges are to realizing this promise", says van Nimwegen.

From precision oncology to infectious diseases - what experts have to say. Three themes of broad significance emerge from the conference's multiple tracks and sessions:

1) From single-cell data to precision oncology: Genome-wide data from single cells have become essential in cancer research and precision oncology. Identifying and interpreting the consequences of mutations in the DNA of individual cells of a tumour is key to classifying the tumour's stage, and to identify appropriate therapies. "Thanks to new techniques which allow us to explore tumours at the level of single cells, we are changing our way to approach cancer: a tumour is now seen as a diverse ecosystem in the context of the surrounding tissue, which opens the door to much more finely targeted therapy", says SIB Group Leader Manfred Claassen (ETH Zurich), co-chair of the single-cell data session;

2) From pathogen sequencing to fighting infectious diseases: Many diseases are caused by rapidly mutating and increasingly drug-resistant microorganisms. Hence characterizing pathogens at the molecular and genomic level is essential for designing drugs and vaccines as well as for the monitoring of disease outbreaks. "Tools such as NextStrain already play an important role for analysing and tracking outbreaks of pathogens such as Ebola or Zika virus in real-time. Public health interventions will increasingly rely on such bioinformatics tools to allocate their resources in the future", says SIB Group Leader Richard Neher (University of Basel), co-chair of the evolutionary medicine session;

3) Biological big data analysis and methods: Ultimately, Big Data obtained from basic research comes from many different sources and in many formats (e.g. sequence, gene expression, and biochemical data). Extracting useful information from such multi-varied data requires precisely tailored tools and methods, including special-purpose machine learning algorithms. "In precision medicine, machine learning techniques are becoming essential - both to integrate the large variety of data types used to characterize each patient, as well as to identify, in these complex high-dimensional data, hidden patterns which may then be used as biomarkers that predict susceptibility to a disease", says SIB Group Leader Julia Vogt (ETH Zurich), co-chair of the multi-level data integration session.

In 2019, [BC]2 will be an integral part of BASEL LIFE, Europe's leading congress in the Life Sciences, taking place at the Congress Center in Basel. The event will thus foster scientific exchanges between computational and experimental disciplines, and between academia and the industry.

Distinguishing the next generation of bioinformaticians: the SIB Awards

The [BC]2 conference will also host the SIB Awards Ceremony, which will, for the 10th time, honor the excellence of two early career researchers - international as well as Swiss-based - as well as of a bioinformatics resource (database or software) of particular importance for the life science community. Such recognition acts as a springboard for young researchers as well as for emerging tools as past awardees told us in a series of interviews.

In many households, it is impossible to imagine life without language assistants - they switch devices on or off, report on news from all over the world or know what the weather will be like tomorrow. The speech recognition of these systems is mostly based on machine learning, a branch of artificial intelligence. The machine generates its knowledge from recurring patterns of data. In recent years, the use of artificial neural networks has largely improved computer-based speech recognition.

For neuroscientist Professor Katharina von Kriegstein from TU Dresden, however, the human brain remains the "most admirable speech processing machine." "It works much better than computer-based speech processing and will probably continue to do so for a long time to come," comments Professor von Kriegstein, "because the exact processes of speech processing in the brain are still largely unknown."

In a recent study, the neuroscientist from Dresden and her team discovered another building block in the mystery of human speech processing. In the study, 33 test persons were examined using functional magnetic resonance imaging (MRI). The test persons received speech signals from different speakers. They were asked to perform a speech task or a control task for voice recognition in random order. The team of scientists recorded the brain activity of the test persons during the experiment using MRI. The evaluation of the recordings showed that a structure in the left auditory pathway - the ventral medial geniculate body, (vMGB) - has particularly high activity when the test persons perform a speech task (in contrast to the control task) and when the test persons are particularly good at recognizing speech.

Previously, it was assumed that all auditory information was equally transmitted via the auditory pathways from the ear to the cerebral cortex. The current recordings of the increased activity of the vMGB show that the processing of the auditory information begins before the auditory pathways reach the cerebral cortex. Katharina von Kriegstein explains the results as follows: "For some time now, we have had the first indications that the auditory pathways are more specialized in speech than previously assumed. This study shows that this is indeed the case: The part of the vMGB that transports information from the ear to the cerebral cortex processes auditory information differently when speech is to be recognized than when other components of communication signals are to be recognized, such as the speaker's voice for example."

The recognition of auditory speech is of extreme importance for interpersonal communication. Understanding the underlying neuronal processes will not only be important for the further development of computer-based speech recognition.

These new results may also have relevance for some of the symptoms of developmental dyslexia. It is known that the left MGB functions differently in dyslexic persons than in others. A specialization of the left MGB in speech may explain why dyslexic people often have difficulty understanding speech signals in noisy environments (such as restaurants). Katharina von Kriegstein and her team are now going to carry out further studies in order to scientifically prove these indications.

More than 50 percent of older Chinese American immigrants experience depressive symptoms linked to increased disabilities and chronic health conditions, according to two new Rutgers studies.

The studies, published in the Journal of the American Geriatrics Society, examine the relationship between psychological well-being and the onset of disability and existence of comorbid chronic medical conditions among a cohort of roughly 3,000 older Chinese Americans aged 60 and older.

Researchers found study participants who reported depressive symptoms were more likely to suffer from onset of functional disabilities - the inability to perform activities of daily living - and mobility issues. They also found that comorbid depression and chronic health conditions increased emergency room visits and hospitalizations, worsened medical prognosis, and led to increased mortality.

"Depressive symptoms have extensive psychological and health consequences for older adults and the greater healthcare community," said lead researcher, XinQi Dong, director of the Rutgers Institute for Health, Health Care Policy and Aging Research. "Our studies suggest a bidirectional relationship between depression and disability, in which the conditions reinforce each other. Further, those suffering from depressive symptoms are more likely to engage in negative health behaviors, such as physical inactivity, obesity, and smoking, and are less likely to adhere to treatment regimens. This behavior further exacerbates their medical conditions and leads to increased use of health services.

"As their physical health declines, older Chinese Americans frequently turn to hospitals and emergency departments to treat their symptoms, which does not address the underlying depression," Dong continued. "Economic implications of increased hospitalizations notwithstanding, without proper screening for depression, symptoms are left underrecognized and untreated, leading to poorer health outcomes and even death."

"What is very evident from these studies is that mental health status compounds the health and well-being of older Chinese Americans and increases their cost of care," said researcher Dexia Kong. "Consequently, the integration of behavioral health and primary care is essential to effectively serve this population and prevent functional disability which even further exacerbates medical treatment."

Key findings:

Approximately 50% and 54% of U.S. Chinese older adults experience various levels of functional disability and depressive symptoms, respectively.

Depressive symptoms are twice as likely to occur in older Chinese Americans suffering from chronic medical conditions like heart disease, stroke, cancer, diabetes, and arthritis.

Comorbid depression and chronic health conditions increase emergency room visits and hospitalizations among older Chinese Americans.

Older Chinese American Women are more likely to experience comorbid depression and chronic health conditions

Comorbid depression is associated with a six-fold higher likelihood of functional disability, a 70% increase in overall medical costs, and a 2.4-fold increase in mortality than those without depression.

"Depression disproportionately affects older Chinese Americans, which puts them at significant risk for developing functional disabilities and chronic health conditions," said Dong. "Our studies demonstrate the need to develop culturally appropriate interventions and screenings to address depressive symptoms and reduce the onset of disability in minority populations. Mental health professionals and primary care providers must work collaboratively to address vulnerable minority populations' diverse care needs. By working together, healthcare providers can provide a more equitable standard of care to all patients."

In a study published in Scientific Reports, a group of researchers affiliated with São Paulo State University (UNESP) in Brazil describes an important theoretical finding that may contribute to the development of quantum computing and spintronics (spin electronics), an emerging technology that uses electron spin or angular momentum rather than electron charge to build faster, more efficient devices.

The study was supported by São Paulo Research Foundation - FAPESP. Its principal investigator was Antonio Carlos Seridonio, a professor in UNESP's Department of Physics and Chemistry at Ilha Solteira, São Paulo State. His graduate students Yuri Marques, Willian Mizobata and Renan Oliveira also participated.

The researchers observed that molecules with the capacity to encode information are produced in systems called Weyl semimetals when time-reversal symmetry is broken.

These systems can be considered three-dimensional versions of graphene and are associated with very peculiar kinds of objects called Weyl fermions. These are massless, quasi-relativistic, chiral particles - quasi-relativistic because they move similarly to photons (the fundamental "particles" of light) and behave as if they were relativistic, contracting space and dilating time.

The term "chiral" applies to an object that cannot be superimposed onto its mirror image. A sphere is achiral, but our left and right hands are chiral. In the case of Weyl fermions, chirality makes them behave as magnetic monopoles, unlike all magnetic objects in the trivial world, which behave as dipoles.

Weyl fermions were proposed in 1929 by German mathematician, physicist and philosopher Hermann Weyl (1885-1955) as a possible solution to Dirac's equation. Formulated by British theoretical physicist Paul Dirac (1902-1984), this equation combines principles of quantum mechanics and special relativity to describe the behavior of electrons, quarks and other objects.

Weyl fermions are hypothetical entities and have never been observed freely in nature, but studies performed in 2015 showed that they can be the basis for explaining certain phenomena.

Similar to Majorana fermions, which also solve Dirac's equation, Weyl fermions manifest themselves as quasi-particles in condensed matter molecular systems.

This field, in which high-energy physics and condensed matter physics converge, has mobilized major research efforts, not only because of the opportunities it offers for the development of basic science but also because the peculiarities of these quasi-particles may one day be used in quantum computing to encode information.

The new study conducted at UNESP Ilha Solteira advanced in that direction. "Our theoretical study focused on molecules made up of widely separated atoms. These molecules wouldn't be viable outside the Weyl context because the distance between atoms prevents them from forming covalent bonds and hence from sharing electrons. We demonstrated that the chirality of electron scattering in Weyl semimetals leads to the formation of magnetic chemical bonds," Seridonio told.

Examples of Weyl semimetals include tantalum arsenide (TaAs), niobium arsenide (NbAs) and tantalum phosphide (TaP).

"In these materials, Weyl fermions play an analogous role to that of electrons in graphene. However, graphene is a quasi-2D system, whereas these materials are fully 3D," Seridonio said.

The theoretical study showed that Weyl fermions in these systems appear as splits in Dirac fermions, a category comprising all material particles of the so-called Standard Model, with the possible exception of neutrinos.

These splits occur at points where the conduction band (the space in which free electrons circulate) touches the valence band (the outermost layer of electrons in atoms).

"A break in symmetry makes this point, the Dirac node, split into a pair of Weyl nodes with opposite chiralities. In our study, we broke the time-reversal symmetry," Seridonio said.

Time reversal symmetry essentially means that a system remains the same if the flow of time is reversed. "When this symmetry is broken, the resulting molecule has spin-polarized orbitals."

In usual molecular systems, spin-up electrons and spin-down electrons are evenly distributed in the electron cloud. This is not the case in Weyl systems.

"The result is a molecule in which the spin-up and spin-down electron clouds are spatially different. This peculiarity can be used to encode information because the molecule can be associated with the binary system, which is the bit or basic unit of information," Seridonio said.

NASA's Aqua satellite provided forecasters at the National Hurricane Center with visible imagery and infrared data on Tropical Storm Dorian as it continued its western track into the Eastern Caribbean Sea. Infrared data provided an indication of the storm's heavy rain making potential.

Watches and Warnings

On Wednesday, August 28, 2019, the National Hurricane Center or NHC noted that a Hurricane Watch is in effect for Puerto Rico, Vieques, Culebra, and the U.S. Virgin Islands. A Tropical Storm Warning is in effect for Puerto Rico, Vieques, Culebra, the U.S. Virgin Islands and the British Virgin Islands. A Tropical Storm Watch is in effect for the Dominican Republic from Isla Saona to Samana.

Infrared Temperatures Indicate Strong Storms

Cloud top temperatures provide information to forecasters about where the strongest storms are located within a tropical cyclone. The stronger the storms, the higher they extend into the troposphere, and the colder the cloud top temperatures. NASA's Aqua satellite analyzed Tropical Storm Dorian's cloud tops to get that information. AIRS found that some areas in Dorian were being affected by dry air, which was sapping the development of thunderstorms.

The NHC noted that 10-mile wide eye feature developed in Martinique and Guadeloupe radar data between 11 a.m. and 12 p.m. EDT (1500-1600 UTC) around the time Aqua passed over Dorian, and then again between 1 p.m. and 2 p.m. EDT (1700-1800 UTC) around the time the Aqua satellite passed overhead.

NASA's Aqua satellite analyzed the storm on Aug. 27 at 1:35 p.m. EDT (1735 UTC) using the Atmospheric Infrared Sounder or AIRS instrument. AIRS found coldest cloud top temperatures as cold as or colder than minus 63 degrees Fahrenheit (minus 53 degrees Celsius) around the center and in a thick band of thunderstorms east of the center. NASA research has indicated that cloud top temperatures that cold indicate strong storms that have the capability to create heavy rain.

Heavy Rainfall Expected

NHC forecasters said that Dorian is expected to produce the following rainfall accumulations:

Western Leeward Islands from Guadeloupe to St. Kitts to Anguilla...1 to 4 inches

Southern and Eastern Puerto Rico and the U.S. and British Virgin Islands...4 to 6 inches, isolated 10 inches

Northwestern Puerto Rico...1 to 4 inches

Haiti and Dominican Republic...1 to 3 inches

Southern Bahamas...1 to 4 inches

Northern Bahamas...3 to 6 inches

Florida Peninsula...4 to 8 inches, isolated 10 inches

This rainfall may cause life-threatening flash floods.

Dorian's Status at 8 a.m. EDT on August 28, 2019

At 8 a.m. EDT (1200 UTC), the center of Tropical Storm Dorian was located near latitude 17.1 North, longitude 64.1 West.

Dorian is moving toward the northwest near 13 mph (20 kph), and this general motion is expected to continue during the next few days. Maximum sustained winds are near 60 mph (95 kph) with higher gusts. Tropical-storm-force winds extend outward up to 60 miles (95 km) from the center. NHC forecasters said some strengthening is expected today, and Dorian is forecast to be near hurricane strength when it approaches the Virgin Islands and Puerto Rico. An Air Force reconnaissance plane just reported an estimated minimum central pressure of 1003 millibars.

Tropical storm conditions are expected and hurricane conditions are possible in Puerto Rico, Vieques, Culebra, and the U.S. Virgin Islands today. Swells are expected to increase later this morning across the U.S. and British Virgin Islands and along the southern coasts of Puerto Rico and Hispaniola, and they could cause life-threatening surf and rip current conditions.

On the forecast track, the center of Dorian will pass over or near the U.S. and British Virgin Islands and Puerto Rico later today, Aug. 28. Dorian is then forecast to move to the east of the Turks and Caicos and the southeastern Bahamas on Thursday, and near or to the east of the central and northwestern Bahamas on Friday and Saturday.

A study conducted by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore and the School of Biological Sciences at Nanyang Technological University, Singapore (NTU Singapore) revealed a common deficiency in existing artificial intelligence methods used to predict enhancer-promoter interactions, that may result in inflated performance measurements. The findings, published in scientific journal Nature Genetics in July 2019, provides an enhanced road map for the understanding of gene regulation.

An enhancer is a short sequence of DNA that works to speed up genetic transcription while a promoter is a piece of DNA which acts to initiate gene transcription. Understanding the interactions between an enhancer and a promoter is critical for gene regulation studies as there is great scientific interest in whether interactions may be dysfunctional in cancer cells, and present an opportunity for clinical intervention. In order to study enhancer-promoter interactions on a large scale and in a cost-effective manner, artificial intelligence methods for predicting such interactions are vital to facilitate researchers in their studies and enable them to extend the availability of such data to new cell types.

In the study conducted by Dr Cao Fan, a research fellow at CSI Singapore, and Dr Melissa J. Fullwood, Principal Investigator at CSI Singapore and a Nanyang Assistant Professor at NTU Singapore, the research team attempted to develop an enhancer-promoter interaction prediction method using existing datasets from TargetFinder, an advanced machine learning method that predicts enhancer-promoter interactions based on transcription factor and histone modification profiles in the window regions between enhancers and promoters. During then, the team observed that enhancer-promoter interactions were predicted at random DNA sequence features in the window regions, indicating high performance.

However, upon careful examination of the TargetFinder datasets, the team realised the reported high performances could be attributed to the high overlap between window regions of positive samples in the datasets, affecting the predicted performance. To mitigate the issue of overlapping samples, the team then evaluated enhancer-promoter interaction methods using a chromosome-split strategy. TargetFinder achieved significantly lower performance with the chromosome-split strategy, which proved that the performance measurements were indeed inflated in the earlier prediction.

The team also examined another method, JEME, a supervised machine learning method that makes use of datasets with significant differences in distance distributions between positive and negative samples to predict enhancer-promoter interactions. Their investigation revealed that JEME too, results in inflated performance measurements due to erroneous use of input data.

"Our study highlights the need for careful experimental design when applying machine learning to genomic research. It is key to properly evaluate an enhancer-promoter interaction method, and take into account the possibility of generating highly inflated performance measurement." said Dr Cao.

"Accurate enhancer-promoter interactions prediction is essential in gene regulation studies in order to facilitate our ability to understand if there are any differences between cancer samples, such as different clinical subtypes of cancers, in order to better develop biomarkers and therapies for cancer in the future," said Dr Fullwood.

Moving forward, the research team will be working on a new accurate machine learning approach for the prediction of enhancer-promoter interactions, and applying the method to the analysis of cancer cohorts in order to understand alterations in enhancer-promoter interactions in cancer.

Tiny nanobots flowing through the body to repair damaged cells. Once supposed to be considered as science fiction, these microrobots are becoming a reality with a slew of experimental trials. It is generally thought that nanoparticles are so tiny that they can roam freely all over the body after administration. However, this is only partly true. In a tumor, nanoparticles can make inroads into tumors only as deep as 100 μm from the vessels. The diffusion of the nanoparticles can be also hindered by several barriers, such as dense tumor tissue, high interstitial pressure, and inhomogeneous vascular distribution. Thus, cancer cells located deep in the tissue may survive, resulting in recurrence.

Interestingly, it is reported that immune cells tend to accumulate at deep tumors. As tumors outgrow blood supply, immune cells are preferentially recruited to a tumor microenvironment to support the blood supply to tumors and tissue remodeling. There have been several attempts to use immune cells to deliver anti-cancer drugs to the regions inaccessible by conventional targeting approaches. Since most of them require time-consuming manipulations to extract, grow, and inject cells, this ex vivo process lowers efficacy of the treatment. Others explored ways to have antibody carrying nanoparticles target immune cells. Again, this approach proves ineffective as nanoparticles bulk up with the chemotherapy drug carried and cannot reach the designations efficiently.

In a paper published in Journal of the American Chemical Society, the joint research team led by Director Taeghwan Hyeon at the Center for Nanoparticles within the Institute for Basic Science (IBS) in Daejeon, Dr. Seung-Hae Kwon at Korea Basic Science Institute in Seoul, and Prof. Nohyun Lee at Kookmin University in Seoul, South Korea reported a novel targeting strategy that allows deep tumor penetration of drug-loaded nanoparticles. They used a "click reaction", a chemical reaction that easily joins molecular building blocks just as two pieces of a seat belt "click" to buckle. "Our idea was to induce the linking of immune cell-targeting antibodies to drug-loaded nanoparticles on the cells, instead of taking them up in the cells or using antibody-nanoparticle conjugates. Most other studies did so and failed to produce satisfactory results," notes Professor Nohyun Lee, the corresponding author of the study.

In a click reaction, chemical reagents enable an easy link of unnatural chemical groups to any site of a target protein with high site-selectivity. In the study, researchers used the click reaction between trans-cyclooctene and tetrazine. Trans-cyclooctene-functionalized antibodies are injected into mice to label tumor-infiltrating immune cells. After a certain time, tetrazine-functionalized mesoporous silica nanoparticles are administered so that they "click" to link up to immune cells. "This click reaction-assisted immune cell targeting (CRAIT) strategy successfully "invaded" the intended areas: Real-time fluorescence imaging of the tumor tissue shows that motile immune cells transport the nanoparticles as seen in Figure 2. Compared to passive targeting, the CRAIT method brought a twofold reduction in the tumor burden in aggressive breast cancer models," explains Dr. Soo Hong Lee, the first author of the study. The nanoparticles loaded with an anticancer drug, doxorubicin, did not affect the viability and migration of the cells.

Director Taeghwan Hyeon, the corresponding author of the study says, "The intratumoral distribution of nanoparticles delivered by the CRAIT method was the key to overcoming limitations of conventional delivery methods. This study will broaden the application of nanomedicines." Since the CRAIT method relies on the click reaction, it can be applied to various delivery vehicles including micelles, liposomes, and other nanoparticles. Additionally, if adequate antibodies are available, various circulating cells can be used as delivery vehicles. Because the circulating cells are involved in various inflammatory diseases, the coverage of the CRAIT method is not limited to cancer. The versatile CRAIT method is simple, which requires modification of antibodies and nanoparticles using well-developed bio-conjugation reaction.