Tech

Information security has drawn considerable attention as the exponential growth of information communication in the era of big data. The stimuli-responsive photoluminescent materials that can quickly switch among different states have been an effective approach to increasing the data security and storage density of such devices. Some smart photoluminescent materials (e.g., transitionmetal complexes, fluorescent supermolecules and dyes), capable of responding to external stimuli with reversible changes in chemical constitutions or superstructures, have been intensively explored as optical data storage media and document encryption systems. However, most of them can only provide broad band photoluminescence (PL) from limited luminescent states, resulting in a relatively low security level and limited coding capacity.

In comparison with broad band PL, stimulated emission with narrow linewidth for easily distinguishable readout, is promising in coding field as a novel cryptographic primitive. Nevertheless, owing to the limitation of the Franck-Condon principle, it has been a great challenge to broadly tailor the lasing wavelength, which is unable to generate multiple lasing states, and thus restricting their applications in high-density information storage and high-security optical encryption.

Very recently, Professor Yong Sheng Zhao's group in the Institute of Chemistry, Chinese Academy of Sciences propose a strategy to achieve multiple responsive lasing emission states for high-security optical encryption by modulating the competition between radiative rate of donor and the rate of energy transfer in FRET microlasers, which is published in National Science Review.

The competitive lasing from the donor and acceptor were reversibly switched by modulating the competition between radiative rate of donor and the rate of energy transfer (Figure 1). At a low pump fluence, there is no lasing emission as a result of insufficient gain. Because the KET is larger than Kr, FRET dominates the deexcitation processes, leading to spontaneous emission from the acceptor. When the pump fluence exceeds the acceptor lasing threshold, majority of the excitation energy captured by donor transfers to the acceptor and lasing from acceptor occurs when population inversion is created. Further increasing of pump fluence induce simultaneous lasing emissions from the donor and acceptor as a result of the approaching of Kr to KET. At an even higher pump fluence, the Kr outpaces the KET and radiative decay from donor begins to dominate the deexcitation processes, resulting in lasing from donor when corresponding population inversion is build-up. Consequently, energy transfer to the acceptor is suppressed and lasing emission from the acceptor disappears due to the inefficient gain. Dynamic lasing action could be well controlled through tailoring the balance between radiative rate of donor and the rate of energy transfer, thus resulting in multiple distinguishable lasing states.

On this basis, the authors realized a novel quaternary coding platform and a proof-of-concept demonstration of cryptographic application was exhibited with an inkjet-printed microlaser array (Figure 2). Data encryption and extraction were demonstrated using a 4×4 microlaser array, showing vast prospect in avoiding the disclosure of security information. The results not only offer a comprehensive understanding of the function-oriented construction of organic composite materials, but also open up a new way to the fabrication of flexible photonic components that can be used for optical recording and information encryption.

Electricity and magnetism have been unified by Maxwell's equations, which is the foundation of a vast amount of modern technologies. Nevertheless, achieving efficient coupling of electric and magnetic properties in solid materials has always been challenging throughout the century. This mainly results from that the magnetic and electric properties originate from, respectively, the spin and orbital dynamics of the electron. With these two dynamics being relatively independent from each other, the magneto-electric coupling is hardly observed in most materials, and the electric and magnetic fields, as external stimuli, tend to affect the material by its spin and orbital behaviors only separately.

The quantum nature of the electron spin makes it promising for application in fields like quantum information processing. Most state-of-the-art approaches to manipulate the spins rely on external magnetic fields, typically magnetic resonance. Although an electric field approach for spin manipulation may outperform in aspects such as spatial resolution, energy efficiency and the trivial structure in device construction, the limitation that the electron spin is insensitive to the external electric field forces one to use electrodes charged with tens of kV and positioned with a gap narrower than the diameter of a human hair in order to achieve it practically. If the coupling between the electron spin and the external electric field can be enhanced by chemical design, the magnitude of the driving electric field can be significantly lowered, allowing more rapid and convenient spin manipulation.

Prof. Shang-Da Jiang from College of Chemistry and Molecular Engineering at Peking University, proposed that thanks to the significant spin-orbit coupling in rare earth ions, one can utilize their atomic orbitals to enhance the coupling between the electron spin and the external electric field and furthermore make possible the spin manipulation with low voltage. Having overcome the common drawbacks of rare earth ions such as poor quantum coherence, the Jiang team achieved high-efficiency coherent manipulation of the electron spin by the electric field. Figure 2 shows the quantum phase of the superposition state of the Ce3+ ion under controlled periodic evolution.

On this basis, the team optimized experimental conditions and realized an efficient controllable quantum phase gate and demonstrated the quantum bang-bang control, quantum Zeno effect and the Deutsch-Jozsa algorithm. The authors consider that the reason the driving voltage in this work was reduced only to 50 V was the limitation of the prepared sample size. If the system can be further miniaturized to the micrometer scale, the manipulation will be possible with even lower voltage and higher efficiency. With the sophisticated chip fabrication technologies in relative industries, accommodating the whole system in an integrated circuit and controlling it from an external interface is expectable. Therefore this work is believed to foreshadow the possibility to fabricate the applicable quantum computation unit with the electron spin.

A tunnel junction is a device consisting of two conducting layers separated by an insulating layer. Classically, the resistance for driving current across an insulating layer is infinite; however, when the insulating layer is thin (~ 1-2 nanometers), charge carriers may tunnel through the insulating layer, due to their quantum nature. When the conducting layers are magnetic, a magnetic tunnel junction (MTJ), whose resistance depends on the magnetic configurations, is obtained. Current MTJs have only two resistance states as they support either parallel or anti-parallel magnetic configurations of the two magnetic layers. The two-state MTJ has been playing a central role in spintronics, a branch of electronics that uses the magnetic moment associated with the spin of the electron in addition to the electron charge used in traditional electronics. Thus, for instance, the two-state MTJ is the main building block of the magnetic random access memory (MRAM).

Now, researchers from Bar-Ilan University's Department of Physics and Institute of Nanotechnology and Advanced Materials, together with a group from Instituto Superior Tecnico (IST), Universidade de Lisboa and INESC Microsystems and Nanotechnologies, have introduced a new type of MTJ with four resistance states, and successfully demonstrated switching between the states with spin currents. The increased number of states is achieved by replacing one of the magnetic layers with a structure in the form of two crossing ellipses.

"As it has recently been shown that structures in the form of N crossing ellipses can support two to the power of 2N states, the current results may pave the way to MTJs with much larger number of resistance states," says Prof. Lior Klein, Chairman of Bar-Ilan University's Department of Physics, who led the Bar-Ilan group including Dr. Shubhankar Das, Ariel Zaig, and Dr. Moty Schultz. Prof. Susana Cardoso led the group from Instituto Superior Tecnico (IST), Universidade de Lisboa and INESC Microsystems and Nanotechnologies, together with Dr. Diana C. Leitao. "Such MTJs may enable novel spintronics devices, e.g., multi-level MRAM which stores data much more densely, or neuromorphic memory that meets artificial intelligence challenges in performing cognitive tasks," adds Klein.

Interlocked molecular species have received considerable attention recently, not only because of their intriguing structures and topological importance, but also because of their important applications as molecular machines and nanoscale devices. Benefiting from the reversible coordination bond, some complicated interlocked structure could be realized by high-yield, one-step processes, for example, [2]catenanes and Solomon knot. Molecular Borromean rings (BRs) are [3]catenanes topoisomers in which none of the component rings are linked, but also cannot be separated without breaking one of the rings (Fig. 1). Linear [3]catenanes is another fascinating interlocked three-ring motif (Fig. 1). Several effective methods for the construction of organic linear [3]catenanes have been presented. However, the feasible strategies for the synthesis of organometallic linear metalla[3]catenanes based on coordination-driven self-assembly are still very rare. Beyond linear [3]catenanes, ring-in-ring complex are also a very rare structural motif, which can be considered as substructures of BRs and key intermediates for the preparation of BRs (Fig. 1).

Recently, Ye Lu, Dong Liu, Yue-Jian Lin, Zhen-Hua Li and Guo-Xin Jin from Fudan University (Shanghai, China) made exciting progress and developed self-assembly of metalla[3]catenanes, Borromean rings and ring-in-ring complex using a simple π-donor unit.

Due to the large electron cloud of the sulfur atom, S-containing heterocyclic compounds usually present stronger stacking interactions than polycyclic aromatic compounds under similar conditions. In order to enhance the stacking interactions, bithiophenyl groups were used as building blocks to replace the widely used phenylene or polycyclic aromatic groups. Meantime, electrostatic interactions between electron-rich (π-donor, D) and electron-deficient (π-acceptor, A) aromatic groups are important driving forces in host-guest chemistry. Metallarectangles or cages based on coordination self-assembly commonly bear several positive charges. Due to Coulombic repulsion, this type of metallarectangles or cages is more suitable for combination with electroneutral or electron-rich guests than with electron-poor cations, and overcoming the Coulombic repulsion between a cationic guest and a cationic host is still a challenge. Bithiophenyl groups are strong D units, thus their introduction into metallarectangles could lead to strong interactions between D units and A units, which is a promising strategy to overcome the Coulombic repulsion and potentially allow introduction of a positively-charged cation inside a positively-charged cationic metallarectangle. Following this logic, if an electron-deficient cation could be introduced into a cationic metallarectangle by taking advantage of strong D-A interactions, it could also be possible to thread a cationic metallarectangle based on A units inside a metallarectangle based on D units, to obtain a heterogeneous D-A ring-in-ring complex.

In this work, a series of Cp*Rh-based (Cp* = pentamethylcyclopentadienyl) homogeneous metalls[2]catenanes, as well as linear metalla[3]catenanes and BRs structure were realized through the use of building blocks based on bithiophenyl groups, a simple π-donor unit (Fig. 2). Bithiophenyl groups play a crucial role in the formation of the homogeneous interlocked structures, namely enhancing the strength of the inter-ring interactions. By taking advantage of strong electrostatic interactions between D and A units, the electron-deficient methylviologen cation was used as a guest molecule to realize reversible conversion between a [2]catenanes and a monomeric rectangle. Furthermore, a cationic metallarectangle based on A units was threaded inside a metallarectangle based on bithiophenyl groups, leading to a heterogeneous ring-in-ring complex (Fig. 3). This method for forming ring-in-ring complex was extended by use of a metallarectangle based on pyrenyl group.

These findings will help the understanding of coordination self-assembly and advance the field of organometallic assemblies.

Electro-optic crystal shows great promise for extensive applications in laser, optoelectronics, and optical communication, such as high-speed E-O switch, modulator, deflector, laser mode-locking, photoetching, laser radar (LIDAR) and so on. With the prosperous development of Terahertz (THz) spectroscopy technique, E-O crystals are employed in this realm for generation and detection of the THz electromagnetic radiation. Although there are some commercial E-O crystals available in the market, further exploration of novel E-O crystals with superior properties is also in great demand for a variety of current applications. However, the discovering of novel electro-optic crystals is sporadic due to lack of theoretical method for the evaluation of E-O effect and the difficulties of large-sized crystal growth for electro-optic coefficient measurement. Hence, the strategy for exploration of novel E-O crystals should be improved.

Herein, to address such an issue, inspired by the well-known powder second harmonic generation (SHG) technique reported by Kurtz and Perry (J. Appl. Phys. 39, 3798 (1968). Times Cited: 4176) who open a highway for the exploration new NLO crystals, a high-efficacy evaluation method using accessible powder samples is proposed, in which second harmonic generation effect, infrared reflectance spectrum, and Raman spectrum are introduced to predict the magnitude of electro-optic coefficient. Particularly, the evaluation method is established on the material in powder form or small crystals in micron size, which can be easily obtained at the onset of experiment. Comparing to traditional method for the measurement of E-O coefficients with large-sized crystal which is difficult and time-consuming, the utilization of powders renders the exploring process to be more efficient.

The calculated electro-optic coefficients of numerous reported electro-optic crystals through this approach give universally agreement with the experimental values, evidencing the validity of strategy. Based on this method, CsLiMoO¬4 is screened as a novel electro-optic crystal and high-quality crystal is grown by the Czochralski technique for electro-optic coefficient measurement with half-wave voltage method, whose result is also comparable to the calculated value. Also, on account of the preferable calculated E-O coefficient and the relationship between E-O effect and macroscopic symmetry of crystal, CLM was selected as a potential E-O crystal. Consequently, this powder method for the evaluation of E-O crystals is not only significant for the further understanding of the E-O coefficient, but also have important implications for the high-efficacy screening of promising E-O crystals. The powder evaluation strategy presented in this work will pave a new avenue to explore promising electro-optic crystals efficiently.

Creeped out by cooties? Grossed out by germs? Squeamish about sickness?

If so, then you might also find yourself engaging in more preventative health behaviors, like frequent handwashing and disinfecting your living environment, during the ongoing coronavirus pandemic.

More than other factors, strong feelings of germ aversion and pathogen disgust are significantly associated with concern about COVID-19 and preventative behavior, according to findings from UConn School of Nursing researchers published in the journal PLOS ONE.

The findings are part of a year-long examination of how behavior and social attitudes change, and what factors influence those changes, when people in the United States are faced with the threat of widespread disease. Supported by a National Science Foundation grant, the study is tracking the well-being, feelings, and behavioral practices of about 1,000 individuals across the country, and more than 18 surveys of the participants have already been conducted since kicking off in March.

"When we feel disgust toward something, our behavioral response is to avoid it and get away from it, but people vary in their experience of disgust," says Natalie J. Shook, a social psychologist, associate professor, and principal investigator for the study. "In thinking about these psychological processes, what we're interested in is whether people who are already more sensitive to potential disease threats are then more inclined to follow prescribed preventative health behaviors."

Shook and her team asked study participants about their overall concerns about COVID-19 and about how often they engaged in preventative health behaviors like physical distancing, frequent hand washing, avoiding touching their face, wearing a facemask, and cleaning and disinfecting.

Participants also answered a series of demographic and social questions, including their age, political and religious values, and socioeconomic status, as well as questions designed to gauge risk factors for the disease - whether they had an underlying health condition that might predispose them to severe illness, whether a family member might be at greater perceived risk, or whether they recently had or believed that they had been ill with COVID-19.

"What we found in our data set was that the most consistent predictors of concern about COVID and then engagement in preventative health behaviors are actually those psychological disease avoidance factors," says Shook.

More than factors like age, perceived risk, or political stance, individuals who indicated strong feelings of germ aversion and pathogen disgust also reported greater concern for COVID-19 and increased participation in preventative behaviors. The researchers also found that the people most likely to be impacted by the virus are not necessarily those most likely to be engaging in preventative behaviors.

"Older participants reported more concern about COVID, which makes sense - they're at higher risk," Shook says. "But when we looked at preventative health behaviors, we weren't necessarily seeing that older adults were engaging more in preventative health behaviors. So, where there was the concern, that wasn't necessarily translating into the behaviors that could protect them."

Individuals with higher incomes were associated with more engagement in physical distancing and cleaning behaviors, but they would also have greater access to resources - like cleaning supplies - and the potential to work from home because of their socioeconomic status, Shook says. Recent illness and general perceived health were also linked with many preventative health behaviors, though the individual reasons could vary, from motivations to prevent others from becoming ill to greater awareness due to recent illness.

Shook and her team say their findings identify a variety of characteristics that may place individuals at risk for contracting and spreading disease during a pandemic.

"We took a really broad approach to looking at the different factors that are related to different preventative health behaviors," says Shook. "The fact we are seeing psychological disease avoidance variables as coming out more consistently - which conceptually was not surprising, that's what they should be doing, but that we're seeing those above and beyond traditional personality traits and demographics - I think might speak to something we could potentially tap into."

Shook and her team hope to release additional findings related to initial survey data - including findings on mental health, job security and financial concerns, and vaccination related to COVID-19 - to be released in the coming weeks and months as their year-long examination continues.

Selective communication among different brain regions is crucial for brain function. But the weak and sparse connectivity of the brain is a big hurdle. During the last decade neuroscientists have identified various means by which this limitation can be counteracted. Now scientists from Iran, Germany and Sweden have identified a new role of bi-directional connections in accelerating the communication between brain regions. They have now presented their results in the scientific journal PLoS Computational Biology.

There are essentially two ways by which weak and sparse connectivity can be countered: either by synchrony or by oscillations. In synchrony mode, many neurons spike together (synchronously) when they transmit stimulation. Together they have a stronger combined effect in the downstream network than they do individually. By contrast, in oscillation mode, network oscillations increase the effective connectivity periodically by modulating the membrane potentials of downstream neurons that are receiving the stimulation.

But the oscillations need to be synchronized in the sender and receiver networks. "It is an open question how such synchronous oscillations may occur in the brain. Some time back we proposed that the resonance property of neuronal networks can be used to generate synchronized oscillations," says Ad Aertsen from the Bernstein Center Freiburg (BCF) of the University of Freiburg. Resonance in a neuronal network means that when this network is stimulated at a specific frequency, the network starts to oscillate and the input has a much bigger impact. This idea is referred to as "communication through resonance (CTR)."

However, CTR posed another problem. It takes several oscillation cycles to build up the resonance in the network. Moreover, such resonance needs to be created at every downstream stage. This means that communication across networks is quite slow. "We thought that synchrony and oscillations provide fast and slow communication modes, respectively. And both can be used in different situations. But we remained wary of this issue," explains Arvind Kumar from the Royal Institute of Technology (KTH) in Stockholm, Sweden.

A possible way to speed up the communication is to reduce the time it takes to build-up the resonance. To this end, the group focused on the anatomical observation of bi-directional connections among brain areas. That is, not only do neurons from the sender network project to receiver neurons, but some neurons from the receiver network also project back to the sender network. "Such bi-directional connections are few, but they are sufficient to support a loop between sender and receiver networks," explains Alireza Valizadeh of Institute for Advanced Studies in Basic Sciences in Zanjan, Iran. An important consequence of such a loop is that resonance can be established in fewer cycles. More importantly even, the loop can amplify the signal and there is no need to build-up resonance in subsequent layers. Hedyeh Rezaei, a PhD-student at Zanjan University and visiting student at the BCF under the auspices of her research project says: "It is remarkable that such a loop of connections between just one resonance pair of sender and receiver networks can speed up the network communication by at least a factor of two."

Ad Aertsen sums up: "These new findings provide support for the idea of 'communication through resonance.' What is important is that these results implicate bi-directional connections between brain regions in a novel function, namely, in shaping more rapid and reliable communication between them."

A joint project led by Kumamoto University (Japan) has discovered a new mechanism for anticancer drug resistance in gastric cancer. Researchers found that the Annexin A6 molecule contained in extracellular vesicles (EVs) is secreted by cancer-associated fibroblasts (CAFs) and taken up by gastric cancer cells, resulting in resistance to anticancer drug treatments. This finding creates new avenues for novel drug development targeting Annexin A6 and cancer-associated fibroblasts (CAFs).

Gastric cancer is the second most common cancer in Japan. For advanced gastric cancer in particular, treatment involves various anticancer drugs but too often they do not sufficiently improve medical conditions.

The tumor microenvironment is the area around cancer cells that consists of various cells and support systems, both physical and biochemical. Within this microenvironment, CAFs are known to enhance the malignant transformation of cancer by secreting various factors.

"Our research found that higher amounts of CAFs in tissues resulted in worse conditions for gastric cancer patients. This was also true in patients with advanced gastric cancer who had been treated with anticancer drugs," said Dr. Tomoyuki Uchihara. "Based on this, we wondered if there was some factor derived from CAFs that induced anticancer drug resistance."

In a cell experiment approximating the conditions of a living human body, gastric cancer cells that were cultivated with a culture of CAFs acquired anticancer drug resistance. Through gene expression analysis in gastric cancer cells, researchers discovered that CAF-EV derived Annexin A6 played an important role in gastric cancer cell resistance to anticancer drugs. EVs are tiny sacs of material surrounded by lipid bilayers (membranes) that are released from cells and involved in cell-to-cell information transmission. The researchers also found that Annexin A6 is rarely expressed in gastric cancer cells themselves and is usually present only in CAFs.

This shows that Annexin A6 is involved in the acquisition of anticancer drug resistance by being taken up by gastric cancer cells via EVs. Further experimental results have suggested that Annexin A6 contributes to anticancer drug resistance by stabilizing the cell adhesion molecule "β1 integrin" on the gastric cancer cell membrane and activating FAK-YAP signaling after being taken up by gastric cancer cells.

"Here we showed that CAF-derived Annexin A6, which surrounds gastric cancer cells, causes resistance to anticancer drug treatments," said research team member, Associate Professor Takatsugu Ishimoto. "As the research progresses, new drugs targeting Annexin A6 and CAFs in gastric cancer are expected."

NASA's Terra satellite gathered infrared data on Tropical Depression 14 as it moves through the Caribbean Sea. Infrared data was used to find the location of the strongest storms.

NASA's Terra satellite uses infrared light to analyze the strength of storms by providing temperature information about the system's clouds. The strongest thunderstorms that reach high into the atmosphere have the coldest cloud top temperatures.

On Aug. 21 at 0315 UTC (Aug. 20 at 11:15 p.m. EDT), the Moderate Resolution Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite gathered infrared data from the depression that found the coldest cloud top temperatures were as cold as or colder than minus 60 degrees Fahrenheit (minus 51.1 Celsius). The strongest storms were mostly on the western side of the storm. However, a fragmented band of thunderstorms extending to the southeast also contained strong storms. NASA research has found that cloud top temperatures that cold can generate heavy rainfall. Some of that heavy rain was affecting Mexico's Yucatan Peninsula.

Several watches and warnings were in effect today, Aug. 21. A Hurricane Watch is in effect from Punta Herrero to Cancun, Mexico. A Tropical Storm Warning is in effect for the Bay Islands of Honduras and from Punta Herrero to Cancun, Mexico. A Tropical Storm Watch is in effect for north and west of Cancun to Dzilam, Mexico.

At 11 a.m. EDT (1500 UTC), the National Hurricane Center noted that the center of Tropical Depression Fourteen (TD14) was located near latitude 16.6 degrees north and longitude 84.1 degrees west. That is about 165 miles (270 km) east of Roatan, Honduras and about 325 miles (525 km) southeast of Cozumel, Mexico.

The depression is moving toward the northwest near 14 mph (22 kph). A slower northwestward motion is expected over the next couple of days, followed by an increase in speed by Sunday and Monday. Maximum sustained winds are near 35 mph (55 kph) with higher gusts.

NHC said, "Strengthening is forecast during the next couple of days, and the depression is expected to become a tropical storm later today.  The system is forecast to be near or at hurricane strength when it reaches the Yucatan Peninsula of Mexico late Saturday.  Some weakening is expected as it moves over the Yucatan Peninsula Saturday night.  Afterward, restrengthening is forecast on Sunday as it moves offshore and enters the southern Gulf of Mexico.

On the forecast track, the center of the depression will move away from the coast of Honduras today and will approach the east coast of the Yucatan Peninsula of Mexico on Saturday.  The center will then cross the northeastern part of the Yucatan Peninsula Saturday night and move over the central Gulf of Mexico toward the northwestern Gulf on Sunday and Monday."

NASA Researches Tropical Cyclones

Hurricanes/tropical cyclones are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For more than five decades, NASA has used the vantage point of space to understand and explore our home planet, improve lives and safeguard our future. NASA brings together technology, science, and unique global Earth observations to provide societal benefits and strengthen our nation. Advancing knowledge of our home planet contributes directly to America's leadership in space and scientific exploration.

For updated forecasts. visit: http://www.nhc.noaa.gov

There are more than 70 species of flavivirus, and many cause diseases in humans and animals, including dengue, Zika and yellow fever viruses. A novel flavivirus identification test that is both fast and sensitive has been validated in Brazil by Mariana Sequetin Cunha and collaborators at the Adolfo Lutz Institute, a leading epidemiological surveillance laboratory that reports to the São Paulo state government.

An article on the topic has been published in Archives of Virology.

The research was supported by São Paulo Research Foundation - FAPESP via a Thematic Project, for which the principal investigator (PI) was Maurício Lacerda Nogueira, and a Regular Research Grant for which the PI was Paulo Cesar Maiorka.

"We set out to improve the monitoring of flaviviruses in Brazil by means of a reliable method. To this end, we used the RT-qPCR assay technique," Sequetin told. RT-qPCR stands for reverse transcription quantitative polymerase chain reaction. The laboratory technique combines reverse transcription of RNA into DNA and amplification of specific DNA targets using polymerase chain reaction. It is considered the gold standard for rapid identification of viruses and is recommended by the World Health Organization for diagnosing infection by SARS-CoV-2.

"Until recently, the main method used in Brazil to identify flaviviruses required inoculating the brains of newborn mice with suspected material sampled from human patients or animals," Sequetin said. "When I joined the Adolfo Lutz Institute as a researcher in 2012, I decided to establish an alternative method that would not require the mice but would submit the patient's blood, serum or viscera sample directly to RT-qPCR."

The key question was whether RT-qPCR would be sensitive enough to detect small amounts of viruses in the samples analyzed. Sequetin recalled that the Adolfo Lutz Institute maintained a large number of deep-frozen mice that had been inoculated in the 1990s and stored at -80 °C. "I extracted genetic material from their brains and sought the threshold for detection of different flaviviruses by preparing increasingly dilute solutions," she said.

The protocol established was shown to be highly sensitive and specific. It can be used to detect the different flaviviruses that occur in Brazil and for viral monitoring in sentinel animals and vectors.

"We're going to test it on new samples that we're receiving. I expect to find flaviviruses not described in the literature, especially in mosquitos," Sequetin said.

By creating conditions akin to the center of the Earth inside a laboratory chamber, researchers have improved the estimate of the age of our planet's solid inner core, putting it at 1 billion to 1.3 billion years old.

The results place the core at the younger end of an age spectrum that usually runs from about 1.3 billion to 4.5 billion years, but they also make it a good bit older than a recent estimate of only 565 million years.

What's more, the experiments and accompanying theories help pin down the magnitude of how the core conducts heat, and the energy sources that power the planet's geodynamo -- the mechanism that sustains the Earth's magnetic field, which keeps compasses pointing north and helps protect life from harmful cosmic rays.

"People are really curious and excited about knowing about the origin of the geodynamo, the strength of the magnetic field, because they all contribute to a planet's habitability," said Jung-Fu Lin, a professor at The University of Texas at Austin's Jackson School of Geosciences who led the research.

The results were published on Aug.13 in the journal Physical Review Letters.

The Earth's core is made mostly of iron, with the inner core being solid and the outer core being liquid. The effectiveness of the iron in transferring heat through conduction -- known as thermal conductivity -- is key to determining a number of other attributes about the core, including when the inner core formed.

Over the years, estimates for core age and conductivity have gone from very old and relatively low, to very young and relatively high. But these younger estimates have also created a paradox, where the core would have had to reach unrealistically high temperatures to maintain the geodynamo for billions of years before the formation of the inner core.

The new research solves that paradox by finding a solution that keeps the temperature of the core within realistic parameters. Finding that solution depended on directly measuring the conductivity of iron under corelike conditions -- where pressure is greater than 1 million atmospheres and temperatures can rival those found on the surface of the sun.

The researchers achieved these conditions by squeezing laser-heated samples of iron between two diamond anvils. It wasn't an easy feat. It took two years to get suitable results.

"We encountered many problems and failed several times, which made us frustrated, and we almost gave up," said article co-author Youjun Zhang, an associate professor at Sichuan University in China. "With the constructive comments and encouragement by professor Jung-Fu Lin, we finally worked it out after several test runs."

The newly measured conductivity is 30% to 50% less than the conductivity of the young core estimate, and it suggests that the geodynamo was maintained by two different energy sources and mechanisms: thermal convection and compositional convection. At first the geodynamo was maintained by thermal convection alone. Now, each mechanism plays about an equally important role.

Lin said that with this improved information on conductivity and heat transfer over time, the researchers could make a more precise estimate of the age of the inner core.

"Once you actually know how much of that heat flux from the outer core to the lower mantle, you can actually think about when did the Earth cool sufficiently to the point that the inner core starts to crystalize," he said.

This revised age of the inner core could correlate with a spike in the strength of the Earth's magnetic field as recorded by the arrangement of magnetic materials in rocks that were formed around this time. Together, the evidence suggests that the formation of the inner core was an essential part of creating today's robust magnetic fields.

Enterococcus, a genus that includes common commensal bacteria found in the gut, harbors a bacteriophage that influences the effects of various cancer immunotherapies in ways that may be clinically relevant, researchers working in mice report. The findings reveal that intestinal, microbe-specific T cell responses to bacteriophages may contribute to anticancer immune responses by cross reacting with tumor-associated antigens. This highlights microbes’ therapeutic potential in the cancer space. Several recent studies have indicated that the gut microbiota plays a role in influencing the cancer-immune set point, which describes the balance between factors that promote or suppress anticancer immunity. Thus, gut microbes have been suspected to be important in the clinical outcome of widely used cancer treatments, including chemotherapy and PD-1 blockade immunotherapy. While it’s speculated that intestinal microbes induce memory T cells that cross-react with tumor-associated antigens, the mechanisms through which microbe-specific lymphocytes contribute to antitumor immune responses remain unknown. Aurélie Fluckiger and colleagues discovered that a bacteriophage that preys upon enterococci intestinal bacteria stimulates an immune response that appears to improve the systemic immune response to anticancer treatments. Fluckiger et al. found that administration of enterococci containing the bacteriophage boosted T cell responses in mice, after cancer treatments. The authors further note that the presence of the bacteriophage in human cancer patients was associated with improved survival following PD-1 immunotherapy.

Scientists have demonstrated a new way to precisely target cells by distinguishing them from neighboring cells that look quite similar.

Even cells that become cancerous may differ from their healthy neighbors in only a few subtle ways. A central challenge in the treatment of cancer and many other diseases is being able to spot the right cells while sparing all others.

In a paper published 20 August in Science, a team of researchers at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center in Seattle describe the design of new nanoscale devices made of synthetic proteins. These target a therapeutic agent only to cells with specific, predetermined combinations of cell surface markers.

Remarkably, these 'molecular computers' operate all on their own and can search out the cells that they were programmed to find.

"We were trying to solve a key problem in medicine, which is how to target specific cells in a complex environment," said Marc Lajoie, a lead author of the study and recent postdoctoral scholar at the UW Medicine Institute for Protein Design. "Unfortunately, most cells lack a single surface marker that is unique to just them. So, to improve cell targeting, we created a way to direct almost any biological function to any cell by going after combinations of cell surface markers."

The tool they created is called Co-LOCKR, or Colocalization-dependant Latching Orthogonal Cage/Key pRoteins. It consists of multiple synthetic proteins that, when separated, do nothing. But when the pieces come together on the surface of a targeted cell, they change shape, thereby activating a sort of molecular beacon.

The presence of these beacons on a cell surface can guide a predetermined biological activity -- like cell killing -- to a specific, targeted cell.

The researchers demonstrated that Co-LOCKR can focus the cell-killing activity of CAR T cells. In the lab, they mixed Co-LOCKR proteins, CAR T cells, and a soup of potential target cells. Some of these had just one marker, others had two or three. Only the cells with the predetermined marker combination were killed by the T cells. If a cell also had a predetermined "healthy marker," then that cell was spared.

"T cells are extremely efficient killers, so the fact that we can limit their activity on cells with the wrong combination of antigens yet still rapidly eliminate cells with the correct combination is game-changing," said Alexander Salter, another lead author of the study and an M.D./Ph.D. student in the medical scientist program at the UW School of Medicine. He is training in Stanley Riddell's lab at the Fred Hutchinson Cancer Research Center.

This cell-targeting strategy relies entirely on proteins. This approach sets it apart from most other methods that rely on engineered cells and operate on slower timescales.

"We believe Co-LOCKR will be useful in many areas where precise cell targeting is needed, including immunotherapy and gene therapy," said David Baker, professor of biochemistry at the UW School of Medicine and director of the Institute for Protein Design.

Approximately four months after the initial description of cases of atypical pneumonia in Wuhan, China, in December 2019, COVID-19 had become a major pandemic threat. By April 12, 2020, around half of the world's population was in lockdown, with 1.8 million officially diagnosed cases. Scientists from the Institut Pasteur, the CNRS, Inserm and Université de Paris conducted a pilot study to evaluate the reliability of several laboratory tests with the aim of gaining a better understanding of the profile of antibody responses to SARS-CoV-2 and how the virus is spreading among the population. Four tests for the detection of SARS-CoV-2 antibodies were developed and evaluated, as well as two tests for the detection of neutralizing antibodies. These tests, known as laboratory assays, are a first stage in epidemiological research on COVID-19. The results of this study were published online on medRxiv on April 24, 2020, then in Science Translational Medicine on August 17, 2020.

Evaluating the prevalence of asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile is a vital part of efforts to contain the outbreak and shed light on how the virus is spreading.

PCR tests are currently widely used in France and worldwide, including by the Institut Pasteur (the National Reference Center for Respiratory Viruses, hereafter referred to as the CNR), to diagnose COVID-19 and to detect and quantify SARS-CoV-2 RNA. These virological tests are essential in identifying and monitoring individuals with active infection.

A number of serological assays are also in use. There are two types:

Antibody detection assays, which show whether an individual has developed antibodies against SARS-CoV-2 proteins and therefore previously contracted the virus.
Neutralization assays, which determine whether an individual has neutralizing antibodies and is therefore immunized against the virus.

The importance of reliable tests

The reliability of these tests is crucial. Several teams from the Institut Pasteur, the CNRS, Inserm and Université de Paris therefore set out to develop serological assays, conducting a pilot study to evaluate the reliability of four detection assays by measuring levels of SARS-CoV-2 antibodies. They also developed two new detection assays, giving them an additional point of comparison. Groups of blood samples were taken from different categories of individuals. These groups, used to evaluate the assays, can be broken down as follows:

samples from 400 pre-pandemic individuals (2017-2019), used as comparative samples to establish the specificity of the assays by ensuring that there were no or very few "false positives";
samples from 51 COVID-19 patients with severe or critical forms, from Bichat Hospital in Paris. These samples determined the sensitivity of the assays and enabled the scientists to study the kinetics of antibody response;
samples from 209 individuals with mild symptoms (such as fever or cough) taken in the Oise département on March 3 and 4, 2020;
samples from 200 asymptomatic blood donors in Oise taken between March 20 and 24, 2020.

Seroprevalence results

Seropositivity (the presence of antibodies) was detected in 32% of individuals with mild signs compatible with COVID-19 in the 15 days before the samples were taken, and in 3% of asymptomatic blood donors.

Antibody response time

The scientists determined the antibody response time in hospitalized individuals with COVID-19. Antibodies appeared 5-6 days after the first symptoms, with neutralizing activity after 7-14 days.

This timeline is probably longer in mildly symptomatic or asymptomatic individuals, and the antibody titers (concentration) are probably lower.

Description and evaluation of the assays

The research teams designed four laboratory assays to evaluate SARS-CoV-2 antibody levels in human serum.

ELISA assays: The two ELISA assays are conventional assays based on the full-length N protein of SARS-CoV-2 (ELISA N) or the extracellular domain of the virus spike protein (S).

Advantages: these assays are based on a technique that can be easily transposed and is used in commercial kits. The ELISA S assay was slightly more sensitive than the ELISA N assay.

For both assays, the question of how they might be used on a large scale or brought to market was raised, since they are currently in-house tests. Assays based on a similar principle have already been marketed and are currently under evaluation by the CNR.The performance of commercial assays is evaluated by the CNR using serum samples determined as negative or positive for SARS-CoV-2 antibodies on the basis of at least two of the serological assays developed at the Institut Pasteur.

S-Flow assay: This assay detects the SARS-CoV-2 spike protein in its natural conformation, at the cell surface. It is highly sensitive and specific. The results were similar to ELISA S, with higher sensitivity for low antibody levels. But the assay requires specialist equipment (a flow cytometer) that is less widely available than the plate readers generally used in medical laboratories. This makes it more suitable for use in epidemiological research rather than large-scale diagnostic testing.

LIPS assay: This "immunoprecipitation" assay uses a different technique from the other tests and detects antibodies binding to SARS-CoV-2 N or S proteins or their subdomains. The test provides detailed profiling of viral protein regions targeted by the antibody response. The assay therefore uses various "target antigens," and the sensitivity of the test varies depending on the antigen detected. For this study, part of N and part of S (S1) were used. This assay can also be used in its current form in most animals.The research teams also developed two assays to detect neutralizing antibodies in serum samples from infected individuals, one using the infectious SARS-CoV-2 virus and requiring access to a BSL3 laboratory, and one based on a "pseudovirus" that can be used without the need for a BSL3 facility.

The neutralization assay with infectious SARS-CoV-2 is more complicated to implement as the virus needs to be handled in a BSL3 laboratory. It uses a fixed dose of the virus which destroys 100% of cells. After mixing it with different serum dilutions, the scientists observe whether the presence of SARS-CoV-2 antibodies is sufficient to neutralize the virus and inhibit viral multiplication, thereby preventing cell destruction.

The research teams also developed a neutralization assay known as Lenti S, based on a non-infectious pseudovirus instead of the SARS-CoV-2 virus. This assay does not require containment in a biosafety laboratory, making it easy to implement on a large scale.

Unlike ELISA-type assays, which detect antibodies, a neutralization assay measures the capability of antibodies to block entry of the virus into cells. It can therefore determine whether an individual has antibodies capable of limiting virus multiplication and likely to confer protection against further SARS-CoV-2 infection. The research teams are keen to adapt this assay so that it can be used for high-throughput testing. Further research will be needed to determine the quantity of neutralizing antibodies likely to confer protection and their persistence over time.

Correlation between the assays

To evaluate the comparative reliability of the assays, the research teams compared them by using three cohorts.

In hospitalized patients, a similar number of positive cases was obtained with the serological assays based on N and S; diagnostic application of the assay to detect anti-S1 antibodies was less sensitive, the aim of the latter being to investigate a correlation with protection.

With the cohort of symptomatic individuals from Oise, the S-Flow and ELISA S assays and the LIPS N+S1 combination provided very similar results and higher detection levels than with the other tests. In the blood donors, positive cases were only detected with the S-Flow and ELISA S assays.

In conclusion:

1. The research teams compared the performances of four SARS-CoV-2 antibody detection assays. In general they worked very well, with differences in sensitivity depending on the test and especially the antigens targeted.

2. With regard to the neutralizing antibody detection assays, the pseudovirus neutralization assay is simple and robust but it requires cell culture facilities and special equipment. Serological assays are used to estimate the level of antibodies binding to the virus rather than anticipate their functionality.

3. The scientists are currently establishing correlations so that they can estimate which blood samples have neutralizing capacity based on the levels of antibodies binding to different parts of the virus.

4. The presence of neutralizing antibodies in the blood is likely to indicate protection against further infection, particularly if the titer is high, but this has not yet been formally demonstrated.

5. Serological tests can be used in epidemiological research to determine seroprevalence among specific groups.

6. There was significant circulation of the virus within the cluster of first cases in Oise: 32% of people with moderate clinical signs compatible with COVID-19 had antibodies.

7. Results of the tests performed on asymptomatic individuals depended on the groups studied and their location. For example, out of the 200 tests performed on asymptomatic blood donors in Oise (individuals exhibiting recent signs are not permitted to give blood), 3% were positive."These assays are used to detect seroprevalence in epidemiological studies and also to diagnose individuals. They are also very useful for fully characterizing serum panels when evaluating commercial tests. This study involved several teams from the Institut Pasteur, working in cooperation with physicians and virologists from the Paris Public Hospital Network (AP-HP) and Inserm, epidemiologists and the French Blood Service (EFS). We would like to think the patients and volunteers who donated blood for this study," emphasize the study's co-authors Marc Eloit, Hugo Mouquet, Olivier Schwartz and Sylvie van der Werf.

"The ELISA N and ELISA S assays are of particular interest in the current context. At the Institut Pasteur, thousands of tests could be carried out each week and the technique could be shared with other laboratories," explains Sylvie van der Werf, Head of the National Reference Center for Respiratory Viruses and joint last author of the study.

"LIPS-type assays have the same sensitivity as ELISA-type assays for the same antigen and are useful for studying in detail the probability of protection against further infection in cohorts of several thousand serum samples to determine which antigens are optimal for high-throughput testing – an approach that will be crucial in managing the easing of lockdown measures. Since this work , we have also extended the use of the LIPS assay to the detection of the infection by seasonal coronaviruses and their role regarding the protection or facilitation regarding SARS-CoV-2 infection," says Marc Eloit, Head of the Pathogen Discovery Laboratory and joint last author of the study.

“Since the beginning of the study in March 2020, the S-Flow assay has been used to study the extent of the humoral response in PCR+ individuals with mild symptoms. We are currently assessing the duration of this response. We are analyzing samples from convalescent individuals collected at different time points post symptom onset” says Olivier Schwartz, Head of the Virus & immunity Unit and joint last author of the study.

Press briefing - April 24, 2020

Source

A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations, Science Translational Medicine, August 17, 2020SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors, MedRxiv, April 24, 2020

Ludivine Grzelak1,2, a, Sarah Temmam3,a, Cyril Planchais4,a, Caroline Demeret5,a, Christèle Huon3, Florence Guivel-Benhassine1, Isabelle Staropoli1, Maxime Chazal6, Jeremy Dufloo1, Delphine Planas1, Julian Buchrieser1, Maaran Michael Rajah1, Remy Robinot1, Françoise Porrot1, Mélanie Albert5,25, Kuang-Yu Chen7, Bernadette Crescenzo5, Flora Donati5,25, François Anna21, Philippe Souque8, Marion Gransagne6, Nicolas Escriou6, Stephane Petres9, Marija Backovic10, Lila Bouadma11,12, Lucie Le Fevre12, Quentin Le Hingrat11,14, Diane Descamps11,14, Annabelle Pourbaix13, Yazdan Yazdanpanah11,13, Laura Tondeur15, Camille Besombes15, Marie-Noëlle Ungeheuer16, Guillaume Mellon17, Pascal Morel18, Simon Rolland19, Felix Rey10, Sylvie Behillil5,25, Vincent Enouf5,25, Marie-Aude Créach20, Pierre Charneau8,21, Arnaud Fontanet15,22, Bruno Hoen23, Timothée Bruel1, Marc Eloit3,24 b*, Hugo Mouquet4 b, Olivier Schwartz1 b* and Sylvie van der Werf5,25 b

1 Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR 3569, Paris, France; Vaccine Research Institute, Creteil, France2 Université de Paris, Paris, France3 Pathogen Discovery Laboratory, Department of Virology, Institut Pasteur, Paris, France4 Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, INSERM U1222, Paris, France5 Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur CNRS UMR 3569; Université de Paris, Paris, France6 Viral Genomics and Vaccination Unit, Institut Pasteur, Paris, France7 RNA Biology of Influenza Virus, Department of Virology, Institut Pasteur, Paris, France8 Molecular Virology & Vaccinology Unit, Department of Virology, Institut Pasteur, Paris, France.9 Plate-Forme Technologique Production et Purification de Protéines Recombinantes, Institut Pasteur, Paris, France10 Structural Virology Unit, Department of Virology, Institut Pasteur, Paris, France; CNRS UMR 3569, Paris, France11 Université de Paris, INSERM UMR 1137 IAME, Paris, France12 Medical and Infectious Diseases Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Bichat- Claude Bernard University Hospital, France13 Department of Infectious diseases, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, France14 Department of Virology, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, France15 Emerging Diseases Epidemiology Unit, Department of Global Health, Institut Pasteur, Paris, France16 Investigation Clinique et Accès aux Ressources Biologiques (ICAReB) , Institut Pasteur, Paris, France17 Unité Coordination du Risque Epidémique et Biologique, AP-HP, Hôpital Necker, Paris, France18 Etablissement Français du Sang (EFS), Paris, France19 Service de maladies infectieuses, hôpital universitaire Cavale Blanche, Brest, France ; CIC 1417, CIC de vaccinologie Cochin-Pasteur, AP-HP, Hôpital Cochin, Paris, France20 Centre d’épidémiologie et de santé publique des armées, Marseille21 Pasteur-TheraVectys joined unit22 PACRI Unit, Conservatoire National des Arts et Métiers, Paris, France23 Direction de la recherche médicale, Institut Pasteur, Paris, France24 National Veterinary School of Alfort, Maisons-Alfort, France25 National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France

Journal

Science Translational Medicine

Light can partake in peculiar phenomena at the nanoscale. Exploring these phenomena can unlock sophisticated applications and provide useful insights into the interactions between light waves and other materials.

In a recent study, scientists at Cornell University propose a novel method by which nanoscale light can be manipulated and transported. These special modes of light transport are known to arise at finely tuned interfaces between slightly different nanomaterials. Minwoo Jung, lead researcher on this study, illustrates this concept through a simple analogy: "A floating tube has a hole in the middle, but a normal balloon doesn't. No matter how you squeeze the round balloon, it cannot be reshaped like a donut-at least not without popping the balloon, re-knitting the rubber, and re-injecting the air. Thus, a tube and a balloon are distinct in their topology because they are not connected through a smooth deformation."

Jung further explains that physicists have been interested in gluing two topologically distinct materials side by side so that one of them acts like a balloon and the other like a tube. This means that, at their interface, a process that connects these two materials must occur, much like the poking/popping/re-knitting/re-injecting from a balloon to a tube. Under the right conditions, this process can give rise to a strong channel for transmitting energy or information along the interface. Because this process can be applied to light (which acts as a carrier of energy or information), this branch of physics is called topological photonics.

Jung and his team combined the fascinating concept of topological photonics with an innovative technique that traps light in an atomically thin material. This method brought together two rapidly emerging fields in applied and fundamental physics: graphene nanolight and topological photonics. Jung says, "Graphene is a promising platform for storing and controlling nanoscale light and could be key in the development of on-chip and ultracompact nanophotonic devices, such as waveguides and cavities."

The research team ran simulations involving a graphene sheet layered on a nanopatterned material that functions as a metagate. This honeycomb-like metagate consists of a solid layer of material with holes of different sizes, centered at the vertices of the hexagons. The varying radii of these holes affect the way in which the photons pass through the material. The scientists found that strategically "gluing" together two different metagates creates a topological effect that confines photons at their interface in a predictable, controllable manner.

Different choices of metagate designs demonstrate the dimensional hierarchy of the device's topology. Specifically, depending on the metagate geometry, nanolight can be made to flow along one-dimensional edges of the topological interface or can be topologically stored at zero-dimensional (point-like) vertices. Moreover, the metagate allows for on-and-off electric switching of these waveguides or cavities. Such battery-operated topological effects can benefit the technological adoption of topological photonics in practical devices.

Jung's team is optimistic that the synergistic combination of graphene nanolight and topological photonics will spur advances in relevant research areas, like optics, material sciences, and solid-state physics. Their graphene-based material system is simple, efficient, and suitable for nanophotonic applications: a step forward in harnessing the full potential of light.