Whats The Effect of TiO2 on the Sintering Behavior of LVTM? (Material Science / Engineering)

By using sintering pot tests, X-ray diffraction (XRD), scanning electron microscopy (SEM), and mineral phase microanalysis, Songtao Yang and colleagues investigated the effects of TiO2 on the metallurgical properties, microstructure, and mineral composition of Low-grade vanadiferous titanomagnetite ore (LVTM) sinter. They found that the lower the TiO2 content, the better the quality of the sinter. Their study recently appeared in the Journal Materials.

Low-grade vanadiferous titanomagnetite ore (LVTM) is as an important mineral resource for sintering ore manufacturing. Furthermore, TiO2 has a significant effect on the sintering process of iron ore fines. But, the sintering behaviours with a relatively higher TiO2 content have not been studied comprehensively. Therefore, it is necessary to investigate the sintering behaviour of LVTMs with high titanium dioxide content.

Thus, Songtao and colleagues explored the effect of TiO2 on the sintering behavior of LVTM. First, they examined the yield (+5 mm), weight loss, flame front speed, productivity, tumbler index (TI), reduction degradation index (RDI), reduction index (RI), and softening properties. Later, they studied mineral compositions and microstructures of the LVTM sinter with different TiO2 contents. Furthermore, they evaluated the sinter with different TiO2 content.

Figure 1. Metallurgical properties of the sinter with various TiO2 contents:(a) RI, (b) RDI, (c) TI. © Songtao Yang et al.

They showed that, as the TiO2 content increased from 1.75% to 4.55%, the flame front speed and productivity decreased, while the reduction degradation index (RDI) and softening properties deteriorated. In addition, the tumbler index (TI) values reached a maximum at TiO2 = 1.75% i.e. it also decreased while, the Reduction Index (RI) improved.

They also showed that, the mineral composition of the LVTM sinter changed considerably when the TiO2 content was varied. As the TiO2 content increased, the magnetite and perovskite phases increased, while the calcium ferrite and hematite phases decreased.

Figure 2. Comprehensive evaluation results of the sinter with different TiO2 contents. © Songtao Yang et al.

Finally, it has been shown that, as the TiO2 content increased, the comprehensive index of the sinter decreased.

“In our study, the appropriate TiO2 content was 1.75%.”

Thus, the lower the TiO2 content, the better the quality of the sinter.

Featured image: Schematic of sintering pot test equipment © Songtao Yang et al.

Reference: Yang, S.; Tang, W.; Xue, X. Effect of TiO2 on the Sintering Behavior of Low-Grade Vanadiferous Titanomagnetite Ore. Materials 2021, 14, 4376. https://doi.org/10.3390/ma14164376

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A Machine Learning Approach For Predicting Risk of Schizophrenia Using A Blood Test (Psychiatry)

An innovative strategy that analyzes specific regions of the genome offers the possibility of early diagnosis of schizophrenia, reports a team led by researchers at Baylor College of Medicine. The strategy applied a machine learning algorithm called SPLS-DA to analyze specific regions of the human genome called CoRSIVs, hoping to reveal epigenetic markers for the condition.  

In DNA from blood samples, the team identified epigenetic markers, a profile of methyl chemical groups in the DNA, that differ between people diagnosed with schizophrenia and people without the disease and developed a model that would assess an individual’s probability of having the condition. Testing the model on an independent dataset revealed that it can identify schizophrenia patients with 80% accuracy. The study appears in the journal Translational Psychiatry.

“Schizophrenia is a devastating disease that affects about 1% of the world’s population,” said corresponding author  Dr. Robert A. Waterland professor of pediatrics – nutrition at the USDA/ARS Children’s Nutrition Research Center at Baylor and of molecular and human genetics. “Although genetic and environmental components seem to be involved in the condition, current evidence only explains a small portion of cases, suggesting that other factors, such as epigenetic, also could be important.”

Epigenetics is a system for molecular marking of DNA – it tells the different cells in the body which genes to turn on or off in that cell type, therefore epigenetic markers can vary between different normal tissues within one individual. This makes it challenging to assess whether epigenetic changes contribute to diseases involving the brain, like schizophrenia.

To address this obstacle, Waterland and his colleagues had identified in previous work a set of specific genomic regions in which DNA methylation, a common epigenetic marker, differs between people but is consistent across different tissues in one person. They called these genomic regions CoRSIVs for correlated regions of systemic interindividual variation. They proposed that studying CoRSIVs is a novel way to uncover epigenetic causes of disease.

“Because methylation patterns in CoRSIVs are the same in all the tissues of one individual, we can analyze them in a blood sample to infer epigenetic regulation on other parts of the body that are difficult to assess, such as the brain,” Waterland said.

Many previous studies have analyzed methylation profiles in blood samples with the goal of identifying epigenetic differences between individuals with schizophrenia, the researchers explained.

“Our study is innovative in various ways,” said first author Dr. Chathura J. Gunasekara, computer scientist in the Waterland lab. “We focused on CoRSIVs and also applied for the first time the SPLS-DA machine learning algorithm to analyze DNA methylation. As a scientist interested in applying machine learning to medicine, our findings are very exciting. They not only suggest the possibility of predicting risk of schizophrenia early in life, but also outline a new approach that may be applicable to other diseases.”

The current study also is innovative because it considered major potential confounding factors other studies did not take into account. For instance, methylation patterns in blood can be affected by factors such as smoking and taking antipsychotic medications, both of which are common in schizophrenia patients.

“Here, we took various approaches to evaluate whether the methylation patterns we detected at CoRSIVs were affected by medication use and smoking. We were able to rule that out,” Waterland said. “This, together with the fact that DNA methylation at CoRSIVs is established very early in life, indicates that the epigenetic differences we identified between schizophrenia patients and healthy individuals were there before the disease was diagnosed, suggesting they may contribute to the condition.”

Using this novel approach, the researchers were able to achieve much stronger epigenetic signals associated with schizophrenia than has ever been done before, said the team.

“We consider our study a proof of principle that focusing on CoRSIVs makes epigenetic epidemiology possible,” Waterland said.

The following authors also contributed to this work: Eilis Hannon and Jonathan Mill at University of Exeter Medical School, Harry MacKay and Cristian Coarfa at Baylor College of Medicine, Andrew McQuillin at University College London and David St. Clair at University of Aberdeen.

This work was supported by NIH/NIDDK (grant number 1R01DK111522), the Cancer Prevention and Research Institute of Texas (grant number RP170295) and USDA/ARS (CRIS 3092-5-001-059).

Provided by Baylor College of Medicine

Proteins Communicating Through the DNA Molecule Constitute A Newly Discovered Genetic “Switch” (Chemistry)

Proteins can communicate through DNA, conducting a long-distance dialogue that serves as a kind of genetic “switch,” according to Weizmann Institute of Science researchers. They found that the binding of proteins to one site of a DNA molecule can physically affect another binding site at a distant location, and that this “peer effect” activates certain genes. This effect had previously been observed in artificial systems, but the Weizmann study is the first to show it takes place in the DNA of living organisms.

A team headed by Dr. Hagen Hofmann of the Chemical and Structural Biology Department made this discovery while studying a peculiar phenomenon in the soil bacteria Bacillus subtilis. A small minority of these bacteria demonstrate a unique skill: an ability to enrich their genomes by taking up bacterial gene segments scattered in the soil around them. This ability depends on a protein called ComK, a transcription factor, which binds to the DNA to activate the genes that make the scavenging possible. However, it was unknown how exactly this activation works.

(l-r) Dr. Nadav Elad, Dr. Haim Rozenberg, Dr. Gabriel Rosenblum, Jakub Jungwirth and Dr. Hagen Hofmann. Twisting a rope from one end © Weizmann Institute of Science

Staff Scientist Dr. Gabriel Rosenblum led this study, in which the researchers explored the bacterial DNA using advanced biophysical tools – single-molecule FRET and cryogenic electron microscopy. In particular, they focused on the two sites on the DNA molecule to which ComK proteins bind.

They found that when two ComK molecules bind to one of the sites, it sets off a signal that facilitates the binding of two additional ComK molecules at the second site. The signal can travel between the sites because physical changes triggered by the original proteins’ binding create tension that is transmitted along the DNA, something like twisting a rope from one end. Once all four molecules are bound to the DNA, a threshold is passed, switching on the bacterium’s gene scavenging ability.

“We were surprised to discover that DNA, in addition to containing the genetic code, acts like a communication cable, transmitting information over a relatively long distance from one protein binding site to another,” Rosenblum says.

By manipulating the bacterial DNA and monitoring the effects of these manipulations, the scientists clarified the details of the long-distance communication within the DNA. They found that for communication – or cooperation – between two sites to occur, these sites must be located at a particular distance from one another, and they must face the same direction on the DNA helix. Any deviation from these two conditions – for example, increasing the distance – weakened the communication. The sequence of genetic letters running between the two sites was found to have little effect on this communication, whereas a break in the DNA interrupted it completely, providing further evidence that this communication occurs through a physical connection.

A 3D reconstruction from single particles of bacterial DNA (gray) and ComK proteins (red), imaged by cryogenic electron microscopy, viewed from the front (left) and at a 90 degrees rotation. ComK molecules bound to two sites communicate through the DNA segment between them © Weizmann Institute of Science

Knowing these details may help design molecular switches of desired strengths for a variety of applications. The latter may include genetically engineering bacteria to clean up environmental pollution or synthesizing enzymes to be used as drugs.

“Long-distance communication within a DNA molecule is a new type of regulatory mechanism – one that opens up previously unavailable methods for designing the genetic circuits of the future,” Hofmann says.

The research team included Dr. Nadav Elad of Weizmann’s Chemical Research Support Department; Dr. Haim Rozenberg and Dr. Felix Wiggers of the Chemical and Structural Biology Department; and Jakub Jungwirth of the Chemical and Biological Physics Department.

Reference: Rosenblum, G., Elad, N., Rozenberg, H. et al. Allostery through DNA drives phenotype switching. Nat Commun 12, 2967 (2021). https://doi.org/10.1038/s41467-021-23148-2

Provided by Weizmann Institute of Science

Potential Drug Against COVID-19 Found Among Tapeworm Medications (Medicine)

Re-engineered compound fights both cytokine storm and viral replication, experiments show.

A group of medications long prescribed to treat tapeworm has inspired a compound that shows two-pronged effectiveness against COVID-19 in laboratory studies, according to a new publication appearing online in the journal ACS Infectious Disease.

The compound, part of a class of molecules called salicylanilides, was designed in the laboratory of Professor Kim Janda, PhD, the Ely R. Callaway, Jr. Professor of Chemistry and director of the Worm Institute for Research and Medicine at Scripps Research, in La Jolla, CA.

“It has been known for 10 or 15 years that salicylanilides work against certain viruses,” Janda says. “However, they tend to be gut-restricted and can have toxicity issues.”

Janda’s compound overcomes both issues, in mouse and cell-based tests, acting as both an antiviral and an anti-inflammatory drug-like compound, with properties that auger well for its use in pill form.

Salicylanilides were first discovered in Germany in the 1950s and used to address worm infections in cattle. Versions including the drug niclosamide are used in animals and humans today to treat tapeworm. They have also been studied for anti-cancer and antimicrobial properties.

The modified salicylanilide compound that Janda created was one of about 60 that he built years ago for another project. When the SARS-CoV-2 virus became a global pandemic in early 2020, knowing that they may have antiviral properties, he started screening his old collection, first in cells with collaborators from Sorrento Therapeutics and The University of Texas Medical Branch, and later, after seeing promising results, working with Scripps Research immunologist John Teijaro, PhD, who conducted rodent studies.

One compound stood out. Dubbed simply “No. 11,” it differs from the commercial tapeworm medicines in key ways, including its ability to pass beyond the gut and be absorbed into the bloodstream—and without the worrisome toxicity.

“Niclosamide is basically digestive-track restricted, and that makes sense, because that’s where parasites reside,” Janda says. “For that reason, simple drug repurposing for a COVID treatment would be counterintuitive, as you want something that is readily bioavailable, yet does not possess the systemic toxicity that niclosamide has.”

About 80 percent of salicylanilide 11 passed into the bloodstream, compared to about 10 percent of the antiparasitic drug niclosamide, which has recently entered clinical trials as a COVID-19 treatment, Janda says.  

The experiments showed that of the many modified salicylanilides he had built in his laboratory, No. 11 affected pandemic coronavirus infections in two ways. First, it interfered with how the virus deposited its genetic material into infected cells, a process called endocytosis. Endocytosis requires the virus to form a lipid-based packet around viral genes. The packet enters the infected cell and dissolves, so the infected cell’s protein-building machinery can read it and churn out new viral copies. No. 11 appears to prevent the packet’s dissolution.

“The compound’s antiviral mechanism is the key,” Janda says. “It blocks the viral material from getting out of the endosome, and it just gets degraded. This process does not allow new viral particles to be made as readily.”

Importantly, because it acts inside cells rather than on viral spikes, questions about whether it would work in new variants like Delta and Lambda aren’t a concern, he adds.

“This mechanism is not dependent on the virus spike protein, so these new variants coming up aren’t going to relegate us to finding new molecules as is the case with vaccines or antibodies,” Janda says.

In addition, No. 11 helped quiet potentially toxic inflammation in the research animals, Janda says, which could be important for treating acute respiratory distress associated with life-threatening COVID infections. It reduced levels of interleukin 6, a signaling protein which is a key contributor of inflammation typically found in advanced stages of COVID-19.

Better medications against COVID-19 are urgently needed, as highly infectious new variants drive renewed surges of illness and death globally. But Janda says salicylanilide No. 11 was created long before the pandemic.

After fighting an unpleasant bacterial infection called Clostridioides difficile about 10 years ago, he saw a clear need for better treatment options. Multi-drug-resistant strains of C. difficile have become a major cause of drug-resistant diarrheal disease outbreaks in health care institutions globally, and among people using antibiotics. As director of the Worm Institute, which focused on parasitic infections, Janda was very familiar with salicylanilides, and knew of their antimicrobial properties. His laboratory created a “library” of modified salicylanilides several of which showed strong efficacy against C. difficile, and the collection was subsequently licensed by pharmaceutical firm Sorrento Therapeutics. Among them was salicylanilide 11.  

“Salicylanilide 11 actually was placed on the back burner in my laboratory against C. difficile because it’s not as gut-restricted as we would like it to be,” Janda says. “But salicylanilide 11 has got a lot of really positive things going for it as a potential therapeutic for COVID.”

In addition to Janda and Teijaro, authors of the study, “Salicylanilides reduce SARS-CoV-2 replication and suppress induction of inflammatory cytokines in a rodent model,” are Steven Blake, Namir Shaabarani, Lisa Eubanks and Nathan Beutler of Scripps Research, Junki Maruyama, John Manning,and Slobodan Paessler of the University of Texas Medical Branch Department of Pathology, and Henry Ji of Sorrento Therapeutics, Inc.

Paessler received funding from Sorrento Therapeutics for the part of the work.

Featured image: Colorized scanning electron micrograph of an apoptotic cell (pink) heavily infected with SARS-COV-2 virus particles (green), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. (Photo credit: National Institute of Allergy and Infectious Diseases/NIH.)

Provided by SCRIPPS

Liquid Water On Mars, The Front of Yes (Planetary Science)

In the last month and a half, some articles have been published in Geophysical Research Letters that question the presence – suggested in 2018 in Science – of a lake of liquid water in the subsoil of Mars. How do the authors of that study counter? We asked two of them, the astrophysicist of INAF of Bologna Roberto Orosei and the geophysicist of the University of Roma Tre Elena Pettinelli

Was it really water? Or maybe ice? Or maybe clay? The all-Italian discovery of a lake of liquid water in the subsoil of Mars , published in the summer of 2018 in  Science  and bounced around in newspapers around the world, has been under attack for some time . How normal it is when the scientific method does its job well: flea at each result to see how far the hypothesis holds. A work that also has aspects of competition, of challenge between different research groups – it is useless to deny it. In the case of the discovery of Martian liquid water – now questioned by some articles published in Geophysical Research Lettersover the course of the summer – we are probably still in the initial phase of the meeting. We therefore went to hear from two of the protagonists of the discovery now in check – the astrophysicist of INAF of Bologna Roberto Orosei and the geophysicist of the University of Rome Tre Elena Pettinelli  – what their point of view is on the ongoing confrontation.

Roberto Orosei, first researcher at INAF IRA in Bologna. Credits: S. Parisini / Media Inaf

Orosei, what happens? Your hypothesis about the presence of liquid water in the subsoil of Mars is becoming the punching bag of Geophysical Research Letters …

Orosei: “It is actually the third article published by Geophysical Research Letters in a few weeks in which an alternative explanation to liquid water is presented for the strong echoes detected by Marsis at the base of the Martian polar cap, and we know that there is a fourth arriving…”.

Friendly fire or enemy fire? I mean: are they researchers on the Marsis team or are they external?

Orosei: “All the articles were written by US authors who are part of the Marsis and Sharad teams (the Italian radar aboard NASA’s Mars Reconnaissance Orbiter), while so far no American or European researcher – apart from us – has published articles in favor of our interpretation. The debate is therefore limited to a group of radar experts on both sides of the Atlantic, while the vast majority of the community stands by. Those who can discuss this topic with competence are not many, given its extreme specificity, so in the end even the way in which the results of a scientific work are presented and disseminated influences the credibility that a theory can have in the community. Unfortunately,

Let’s go in order. Last June’s coup, the one launched by Aditya Khuller and Jeffrey Plaut , was based on an expansion – geographic and chronological – of the sample of data analyzed, right? Going to suggest that there might be ice down there, not liquid water. How does it counter?

Orosei: «The discovery of a first area with high radar reflectivity under the south polar cap of Mars was made by Plaut himself in 2007. A couple of years later an article with French and American authors, including Plaut, involved in his conclusions that the cause of these intense reflections was the presence of CO 2 on the ice surface , which is very transparent to radio waves: the strong echoes would therefore be due to the transparency of the overlying material, not to an anomalous composition at the base. When we started working on the water article we had these results in mind, and we took care to demonstrate that there was no CO 2 ice.on the surface. None of us ever claimed that strong radar echoes automatically imply the presence of water, and indeed we tried to consider all plausible alternatives, ultimately proving that these did not explain the properties of the radar signal. The recent article by Khuller and Plaut does not subvert our interpretation, because it does not say anything new from the point of view of the analysis of the radar signal, but it has the merit of identifying other areas where to concentrate our efforts to verify whether there may be or less water presence “.

Elena Pettinelli, full professor at the University of Roma Tre. Source: uniroma3.it

Another criticism is that the salt present under Mars would not be enough to explain the liquid state… Pettinelli, don’t you convince you?

Pettinelli: «It is known that on Mars different types of salts, especially perchlorates, are ubiquitous, so it is plausible that they are also found below the south polar cap where we have detected particularly strong radar echoes. These perchlorates are particular salts that lower the crystallization temperature of water by many tens of degrees (even 80 ° C). Laboratory experiments say that some of these salts also have the particular characteristic of keeping water in a subcooled state down to -120 ° C. So the explanation of the salt water is not in contradiction with the low temperature ».

Now this second attack, much more direct, is launched by Isaac Smith and colleagues , based instead on laboratory tests and analysis, they write, not only of the real part – as you did – but also of the imaginary part of the detected dielectric constant. from the radar. And the bottom line, this time around, is that there is a particular type of clay down there, smectic clay. Is it plausible?

Pettinelli: «The dielectric properties of clays, especially smectites, have been extensively studied since the 1960s for the most diverse reasons: from the study of confined water, to the use of clays to confine radioactive waste. Therefore the dielectric behavior of clays as a function of temperature, frequency and the presence of water is known. In particular, the measurements published in the literature say that at the low temperatures typical of the base of the Martian polar cap the dielectric permittivity, both the real and the imaginary part, are very small and cannot explain the strong echoes detected by Marsis. In essence, the measurements reported by Smith and colleagues are not in agreement with the existing literature and, more importantly,

Here, however, it seems they have taken a liking to it. Do you expect a new attack? From where?

Orosei and Pettinelli: «There was a presentation at a conference in which it was argued that the origin of the echoes seen by Marsis was caused by the resonance of thin layers of CO 2 ice . An article on this subject has not officially been published yet, but there is a preprint on a public archive. We have also examined this possibility and we have remained rather skeptical ».

And you? Are you going to react? Are you preparing a defense of your hypothesis?

Orosei and Pettinelli: «We already have two articles submitted to journals that address the objections raised by the articles in Geophysical Research Letters and a third will be sent shortly. We are reasonably certain that we can rigorously refute the alternative hypotheses to the presence of water. As we said above, the debate is only just beginning ».

To know more:

Provided by INAF

Whats The Effect of Hemp Fiber Surface Treatment on the Water Resistance and Reaction to Fire of Reinforced PLA Composites? (Material Science)

Recently, due to environmental issues and increasing concerns about global energy, natural plant fibres that can replace traditional synthetic fibres as reinforcements in degradable composite materials have received increased attention. Compared to synthetic fibres, plant fibres are more abundant and with greater output. Moreover, as reinforcements in composites, they have a high specific strength, high modulus and are lightweight, cost-effective, as well as environmentally friendly.

Studies have shown that hemp fiber can be a suitable natural reinforcing material for composite application due to its vast availability, price stability, low density, delicate fineness, high toughness and good heat resistance. Furthermore, PLA is a biodegradable material that has wide applications and demonstrates the highest strength among all currently available degradable polymers. Natural fibres reinforced with biodegradable polymers are truly ‘green’ composites. The advantages of using such composites include lower power consumption and lower greenhouse gas emissions. Life cycle assessment (LCA) studies have revealed the potentially significant benefits of green hemp fibre composites compared to glass fibre composites, especially in automotive and transportation products. Therefore, composites fabricated from hemp fibres and PLA are truly ‘green’ composites that fundamentally solve the shortage of raw materials caused by petroleum issues and address environmental problems caused by garbage pollution.

Recent study assessed the fire resistance characterization of hemp fiber reinforced polyesters and reported that the increase in the composite hemp fiber volume contributed to the formation of an effective thermally insulating char layer. However, based on current knowledge, there is no recent study about the fire behavior of hemp fiber reinforced PLA composites and the effect of surface treatments on the composite fire reaction. The characterization of the fire resistance would increase the consideration of natural fiber reinforced composites in construction and demanding transportation (automobile/ aeronautical) applications.

Thus, Alao and colleagues investigated the effects of surface pretreatment (water and alkali) and modification with silane on moisture sorption, water resistance, and reaction to fire of hemp fiber reinforced polylactic acid (PLA) composites at two fiber loading contents (30 and 50 wt.%).

They evaluated moisture adsorption at 30, 50, 75 and 95% relative humidity, and determined water resistance after a 28-day immersion period. In addition, they used the cone calorimetry technique to investigate response to fire.

They showed that, moisture behaviour and reaction to fire of hemp fiber reinforced PLA composites were found to largely depend on the PLA/fiber content and fiber surface (pre)treatment.

They also found that, alkali pretreatment and silane modification not only improves the fiber dispersion and homogeneity within the composites, but also decrease the composite’s hydrophilic characteristics. Additionally, it has been shown that the water pretreatment has little effect on the composite studied characteristics; however, the further silane modification produced significantly higher moisture resistance and better reaction to fire, which may be attributed to the extra removal of the amorphous cell wall content and silane coupling at the hemp fiber surface. The Oswin model accurately predicted the adsorption isotherm for all composites.

“Overall, increasing the fiber amount from 30 to 50 wt.% increased the composite sensitivity to moisture/water, mainly due to the availability of more hydroxyl groups and to the development of a higher pore volume, but fire protection improved due to a reduction in the rate of thermal degradation induced by the reduced PLA content.”

Moreover, with the help of the new Oswin’s model they predicted the composite adsorption isotherm. They found that, 30 wt.% alkali and silane treated hemp fiber composite had the lowest overall adsorption (9%) while the 50 wt.% variant produced the highest ignition temperature (181 ± 18 °C).

Figure 1: Surface temperature and temperature response behind the neat PLA and composites at (a) 30%;(b) 50% hemp fiber content. © Authors

Finally, they demonstrated that, the combined surface treatments of the fibers primarily improved the composite fire protection qualities. Overall, the alkali pretreatment of hemp fibers and surface modification with silane led to the most promising results for the use of hemp reinforced PLA composites. However, considering the expense of silane agents, a simple alkali treatment may be sufficient to efficiently increase the considered properties.

“Our study shows that adequate hemp fiber surface treatment allows the improvement of the composite durability during service, which opens opportunities for the use of sustainable composites in the transportation and construction sectors.”

— they concluded.

Featured image: Schematic representation of the research objective. © Authors

Reference: Alao, P.F.; Marrot, L.; Kallakas, H.; Just, A.; Poltimäe, T.; Kers, J. Effect of Hemp Fiber Surface Treatment on the Moisture/Water Resistance and Reaction to Fire of Reinforced PLA Composites. Materials 2021, 14, 4332. https://doi.org/10.3390/ma14154332

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A Surgical Innovation in Thyroidectomy Spares Patients from Highly Visible Scars (Medicine)

Conventional thyroidectomy is associated with an anterior neck scar ranging from 1 to 2 inches in length—a highly visible reminder to patients of their thyroid disease and a marker to others about their medical histories. Although thyroidectomy has been performed for 150 years, surgeons have only recently begun to apply endoscopic tools to tunnel to the thyroid from other locations to avoid the visible scar on the lower neck.

Initially pioneered in Asia, these endoscopic techniques include the TOETVA (transoral endoscopic thyroidectomy vestibular approach). “The TOETVA procedure was a milestone in that it eliminated a skin incision and scar from thyroidectomy by putting the incisions inside the mouth under the lower lip area,” says Insoo Suh, MD, associate professor of surgery at NYU Grossman School of Medicine. Dr. Suh was among the first U.S. surgeons to travel to Asia to study this technique and introduce it on the West Coast through a program at the University of California San Francisco. “However, the original TOETVA technique may have limitations, including the size of the specimen that can be removed through the middle incision without disruption as well as prolonged discomfort at the chin.”

Now at NYU Langone Health, Dr. Suh is continuing to pioneer the application of endoscopic techniques to thyroidectomy and to research the subject of surgical innovation more broadly. “My major research interests focus on innovative surgical techniques and alternative treatment technologies. I believe that we’re at the forefront of innovating upon the current techniques to make them even safer, better tolerated, and faster.”

TOaST: A Modified Transoral Approach

Dr. Suh and his colleagues have developed a modified transoral procedure that eliminates the need for significant dissection of the chin by creating an effectively invisible submental incision. The new approach, known as the transoral and submental technique (TOaST), reduces the potential for dissection-related complications of the type associated with TOETVA and shortens the path from the incision to the thyroid gland by substituting the submental incision for the central intraoral incision used in the TOETVA procedure.

In an article in the Journal of Surgical Research, Dr. Suh reported on the initial experience of 14 TOaST procedures between 2017 and 2018. Subjects included five patients with benign thyroid nodules, three with cytologically indeterminate nodules, three with papillary thyroid cancers, two with Graves’ disease, and one patient with a multinodular goiter. The technique was demonstrated to be safe in this series, with an extremely low rate of complications overall and no permanent complications such as recurrent laryngeal nerve injury and neck hematoma. The cosmetic results were outstanding.

Dr. Suh’s subsequent, larger experience with this technique has confirmed the safety and efficacy results from this initial case series as well as its potential broader applicability to selected patients. “About half of patients in a typical high-volume endocrine practice would be candidates for the procedure under currently accepted selection criteria,” Dr. Suh says.

Scarring Not a “Minor Concern” for Patients

Although the TOaST procedure does leave a scar, it is functionally invisible, placed in the submental area that is often the incision site for aesthetic procedures such as neck lifts and liposuction. “The idea of a visible scar is not a minor concern,” says Dr. Suh, who is a fierce patient advocate concerning the scar associated with conventional thyroidectomy and the impact it can have on patient satisfaction and self-perception.

“There’s a common theme that comes out of my conversations with most of these patients: it’s not about vanity, but rather about seeing the scar every day in the mirror, reminding the patient of the disease and unavoidably sharing private health information so visibly with the world,” says Dr. Suh. He likens the extra effort to avoid scarring as analogous to reconstructive breast surgery after a mastectomy rather than to other types of aesthetic surgery.

In a recent discrete choice experiment published in Thyroid, Dr. Suh and his colleagues found that, while the risk of nerve injury, travel distance, and cost remain the most important factors for patients choosing among various surgical approaches for thyroidectomy, cosmetic considerations also influence choices depending on patient age. Younger patients (defined as up to 60 years old) are significantly more likely to choose surgical approaches with no visible neck scar and are actually willing to accept significant trade-offs to achieve this outcome, such as more than $2,000 in increased out-of-pocket cost, nearly 700 miles in extra travel distance for surgery, and even a slightly higher rate of complications.

Despite the significance of the study, Dr. Suh cautions against overinterpretation of some of the findings. “For example, patients may be willing to tolerate an increased risk of complications, but that doesn’t necessarily mean that we should as surgeons,” he says. “Thankfully, this is a moot point because these techniques appear to be very safe. I think the most important takeaway here is that visible scars matter to many people, and so it is our duty to respect that by working to address this issue for our patients.”

Featured image: Endocrine surgeon Dr. Insoo Suh and colleagues have developed TOaST, a modified transoral approach to thyroidectomy, which eliminates the need for significant dissection of the chin. PHOTO COURTESY OF DR. INSOO SUH

Provided by NYU Langone

Combination of Experimental Drug Classes Shown to Extend Survival in Mice with Lung Cancer (Medicine)

combination of experimental drugs increased the attack of immune cells on non-small cell lung cancer (NSCLC) to extend survival in mice, a new study found.

Led by researchers at NYU Grossman School of Medicine and its Laura and Isaac Perlmutter Cancer Center, the study results revolve around the immune system, and specifically T cells, which can destroy cells infected with foreign organisms like viruses. The immune system also recognizes cancer cells as abnormal, but tumors produce proteins that turn down immune responses, while immunotherapies seek to counter immune suppression and enhance T cell assault.

Published online August 5 in Cancer Discovery, the new study focused on the effect of a compound called SHP099, which blocks the action of SHP2, an enzyme that plays a critical role in pathways abnormally activated in specific cancer types. Although SHP099 is a “tool compound” that itself cannot be used in patients, several SHP2 inhibitors are in clinical trials for a variety of cancers.

The action of SHP2 is required for efficient activation of KRAS—a molecular switch that becomes “stuck in growth mode” to cause cancerous growth. In the current study, SHP099 treatment of mouse lung tumors caused by a mutant KRAS prevented them from growing; during the same time period; untreated tumors increased in size by 150 percent. These findings showed that at least some T cells in these mice were capable of killing tumor cells. Their effects were limited, however, as the tumors ultimately regrew and killed the mice, which led the study authors to suspect that another cell population might be interfering with T cell action.

The researchers then found that, in addition to its beneficial effects, SHP2 inhibition also causes an influx of granulocytic myeloid-derived suppressor cells (gMDSCs) into tumors, which signal T cells to switch into a type that does not attack tumors well. Subsequent experiments showed that SHP2 inhibition with SHP099 caused cancer cells to produce specific “chemokines,” signaling molecules that attract cells to the source of production, in this case, tumor cells. The chemokine produced upon SHP099 treatment function by binding a surface protein (receptor) on gMDSCs called CXCR2. The infiltrating gMDSCs then impaired the anti-tumor actions of T cells.

To overcome this inhibition, the researchers then tried combining SHP099 with a CXCR2 inhibitor, SX682, designed by Syntrix Pharmaceuticals and currently in clinical trials. This combination significantly reduced gMDSC infiltration compared with SHP099 alone and completely suppressed tumor growth after two weeks of treatment, the time point at which tumor-bearing mice treated with an inert molecule (vehicle) for comparison started to die. The combination also prolonged the survival (median: 38 days) as compared to SHP099 alone (median: 27 days) or just SX682 (median: 21.5 days), and more than doubled overall survival compared with vehicle-treated (median: 18 days) mice. The team found no toxicity after five weeks of combination treatment.

“Our study results showed how one targeted drug could address a weakness in the other, creating a stronger anti-cancer immune environment around tumors,” says co-corresponding author Kwan Ho Tang, PhD, a research scientist in the laboratory of Benjamin G. Neel, MD, PhD, director of Perlmutter Cancer Center. “We would argue that this combination should be tried together in a clinical trial.”

Experiments by the team confirmed that SHP2 inhibition itself causes an influx into tumors of gMDSCs, which are part of normal immune defenses but are changed by signals given off by tumors. The abundance of the gMDSCs in patients with cancer have been linked by past studies to reduced overall survival in multiple solid tumor types.

“We also found in experiments in human NSCLC cells that the influx of gMDSCs brought about by SHP2 inhibitors through CXCR2 may be sabotaging the ability of other emerging drug classes to harness T cell attack as well,” says co-corresponding author Kwok-Kin Wong, MD, PhD, the Anne Murnick Cogan and David H. Cogan Professor of Oncology in the Department of Medicine at NYU Langone Health and director of the Division of Hematology and Medical Oncology. “These may include MEK inhibitors, a newly FDA-approved drug designed to interfere with a single cancer-causing mutant protein called G12C present in many lung cancers, as well as EGF receptor inhibitors, an important treatment for patients with lung tumors carrying mutations in the EGFR gene.”

Finally, say the authors, the study suggests that additional “immune checkpoint” inhibitors could be added to the study combination in future examinations. The immune system uses “checkpoints”—sensors on immune cells that turn them off when they receive the right signal—to spare normal cells from immune attack. Cancer cells hijack checkpoints to turn off immune responses.

Along with Dr. Tang and Dr. Wong, the study was led by co-corresponding author Dr. Neel, and by first author Shuai Li. Other NYU Langone study authors are Jayu Jen, Han, Kayla Guidry, and Ting Chen at Perlmutter Cancer Center; Cynthia Loomis in the Department of Pathology; and Aristotelis Tsirigos, Alireza Khodadadi-Jamayran, and Yuan Hao in the Applied Bioinformatics Laboratories. Other study co-investigators are John Zebala and Dean Maeda of Syntrix Pharmaceuticals; James Christensen and Peter Olson of Mirati Therapeutics; Argus Athanas of Monoceros Biosystems, Inc.; and Carmine Fedele of the Novartis Institutes for BioMedical Research. The study was funded by National Institutes of Health grants P01CA229086, R01CA252239, CA49152, CA248896, and P30 CA016087.

Dr. Wong holds equity in G1 Therapeutics and Recursion Pharmaceuticals; has sponsored research agreements with Mirati Therapeutics, Takeda, BMS, Merus, Alkermes, Ansun Biopharma, Tvardi Therapeutics, Delfi Diagnostics, and Dracen Pharmaceuticals; and has consulting agreements with Allorion, AstraZeneca, Genocea, Epiphanes, Hillstream, Novartis, Merck, Recursion, Navire, Mirati, Prelude, Ono, Janssen, Pfizer, and Zentalis. Dr. Neel holds equity in, and receives consulting fees from, Navire Pharma and Jengu Therapeutics, and holds equity in Northern Biologics, Arvinas, and Recursion. He also has a sponsored research agreement with Mirati and received consulting fees from MPM Capital and Gerson Lehrman Group. His spouse holds equity in Amgen and held equity in Moderna and Regeneron at times during the current study. These relationships are being managed in keeping with the policies of NYU Langone.

Featured image: Perlmutter Cancer Center researchers find a combination of experimental drugs increases the attack of immune cells on non-small cell lung cancer to help extend survival in mice. PHOTO: ROGER HARRIS/SCIENCE PHOTO LIBRARY/GETTY

Reference: Kwan Ho Tang, Shuai Li, Alireza Khodadadi-Jamayran, Jayu Jen, Han Han, Kayla Guidry, Ting Chen, Yuan Hao, Carmine Fedele, John A Zebala, Dean Y Maeda, James G Christensen, Peter Olson, Argus Athanas, Cynthia A Loomis, Aristotelis Tsirigos, Kwok-Kin Wong and Benjamin G Neel, “Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC”, Cancer Discovery, 2021. DOI: 10.1158/2159-8290.CD-21-0369

Provided by NYU Langone

How Primordial Blackholes Forms From The Gauss-Bonnet-Corrected Single Field Inflation? (Cosmology)

Countless number of primordial blackholes formation scenarios have been already discussed by us on our website. Now, Shinsuke Kawai and Jinsu Kim proposed another interesting mechanism for the primordial blackhole formation. They considered a model in which a scalar field is coupled to the Gauss-Bonnet term, and showed that primordial blackholes may be seeded when a scalar potential term and the Gauss-Bonnet coupling term are nearly balanced. Large curvature perturbation in this model not only leads to the production of primordial blackholes but it also sources gravitational waves at the second order. Their study recently appeared in Arxiv.

Cosmic inflation provides a natural framework for the production of primordial blackholes. Single field inflation is capable of generating large primordial curvature perturbation in small scales compared to the scale of the cosmic microwave background. In the single field inflation models for which the primordial blackhole production and the secondary gravitational waves are studied, the gravity sector is usually assumed to be the Einstein gravity. The Einstein gravity however is by no means a complete theory. From the effective field theory viewpoint, for example, higher curvature terms are expected to arise. One such higher curvature term is the Gauss-Bonnet term,

which leads to a relatively well-behaved theory of higher curvature gravity.

Previously, Shinsuke Kawai and Jinsu Kim investigated a model in which a scalar field ϕ is coupled to the Gauss-Bonnet term and discussed the features of a de Sitter-like fixed point as an alternative to cosmic inflation; in the presence of the Gauss-Bonnet coupling term there may exist a nontrivial de Sitter-like fixed point where the scalar potential term is balanced with the higher curvature Gauss-Bonnet term. Near the nontrivial fixed point, the standard slow-roll approximation is invalid and the ultra-slow-roll regime of inflation naturally arises. Furthermore, they pointed out that the primordial curvature power spectrum may become enhanced near the nontrivial de Sitter-like fixed point, which potentially leads to production of primordial blackholes.

Now, they investigated the production of primordial blackholes and the scalar-induced second-order gravitational waves in such a setup.

FIG. 1. The curvature power spectrum is shown for their two benchmark parameter sets. The enhancement is observed as the inflaton enters the ultra-slow-roll regime near the non-trivial fixed point. Here k∗ = 0.05 Mpc¯1 © Kawai and Kim

By considering two benchmark parameter sets they showed that, a large enhancement occurs in the curvature power spectrum by numerically solving the equations of motion.

A mode with large enhancement of the curvature perturbation may experience gravitational collapse when reentering the horizon, thereby producing primordial blackholes. For their two benchmark sets, they computed the present abundance of primordial blackholes. One set accounts for the totality of the dark matter relic density today, while in the other case primordial blackholes constitute only a portion of the present dark matter relic abundance.

FIG. 2. The density parameter of the scalar-induced second-order gravitational waves is shown for their two benchmark sets. The gravitational wave signal of Set 1 is well within the reach of the sensitivity bound of future experiments such as LISA, DECIGO, and BBO. In the case of Set 2, the signal crosses the sensitivity bound of SKA as well. © Kawai and Kim

A large curvature perturbation that leads to the production of primordial blackholes inevitably source the scalar-induced second-order gravitational waves. They also obtained the present density parameter of the gravitational waves by utilizing the approximated analytical expression together with their numerical results of the curvature power spectrum. Both of their two benchmark sets are found to be within the sensitivity bounds of future gravitational wave experiments such as LISA, DECIGO, BBO, and SKA.

“While we focused on the scalar potential of the natural inflation model and assumed a smeared step function for the Gauss-Bonnet coupling function in this work, some of the features that we have found are generic. When there is a balance between a scalar potential term and a Gauss-Bonnet coupling term, a nontrivial fixed point may exist. Near the nontrivial fixed point the ultra-slow-roll inflation generically occurs, during which period a large enhancement of the curvature perturbation is guaranteed. We thus expect that the production of primordial blackholes and the secondary gravitational wave signals are natural in higher curvature gravity theories.”

— they concluded.

Reference: Shinsuke Kawai, Jinsu Kim, “Primordial blackholes from Gauss-Bonnet-corrected single field inflation”, Arxiv, pp. 1-9, 2021. https://arxiv.org/abs/2108.01340

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