Tag: Japan

New insight into a key protein could lead to novel treatments for diseases such as contact dermatitis and asthma

The CCL17/TARC chemokine is involved in many immune-mediated diseases, and is a well-known biomarker of atopic dermatitis. However, the proteins that regulate CCL17 expression are not clear. Recently, scientists from Japan conducted experiments on cultures of dendritic cells focusing on PU.1, a key protein regulating gene expression in immune cells. Further experiments on mice showed that externally regulating PU.1 can alleviate certain asthma symptoms, hinting at potential therapeutic targets for hyperimmune diseases.

Allergies and many other types of immune system-related diseases originate from an interplay of complex chemical pathways that affect cell behavior, distribution, and development. One prominent example is the CCL17/TARC chemokine, a protein that contributes to allergy by attracting certain types of white blood cells, such as T cells and eosinophils. Despite the important and proven roles of CCL17/TARC in allergic diseases like contact dermatitis, not much is known about the transcription factors (proteins that regulate gene expression) involved in regulating the expression of the CCL17 gene.

To address this knowledge gap, a team of scientists from Japan conducted a detailed study, the results of which were published in Allergy, focusing on PU.1, a transcription factor known to regulate gene expression in various types of immune cells. Prof. Chiharu Nishiyama from Tokyo University of Science (TUS), who headed the study, explains why they targeted this specific protein: “A long time ago, we discovered that forced expression of PU.1 in certain types of blood cell lineages causes them to change into dendritic cells. Since then, I have developed a deep interest in the fact that PU.1 is a master transcription factor that regulates dendritic cell differentiation and gene expression.”

The team conducted a series of detailed experiments to clarify, at the molecular level, the relationship that exists between CCL17, PU.1, and other associated transcription factors and promoters. They relied on small interfering RNAs (siRNAs), or short chains of nucleotides that interrupt the translation process (making proteins from a copied DNA segment into RNA) of a target protein with great precision, for their study.

After targeting PU.1 with siRNAs in dendritic cell cultures, they observed a decrease in expression not only for PU.1 and CCL17 but also IRF4 and IRF8, two partner molecules of PU.1.

Through further experiments in cell cultures followed by computational analysis, the team found that IRF4 and PU.1 work together synergistically to activate the transcription (copying of a DNA segment into RNA) of TARC in dendritic cells through the regulatory region of the CCL17 gene. Although this regulatory mechanism appears to be preserved across mammals, the scientists also discovered that the human CCL17 gene contains an additional promoter that is activated in keratinocytes, the most common type of cell found in the outermost layer of our skin.

Finally, the scientists tested the effects of PU.1 suppression in vivo using an asthmatic mouse as a model. They found that a simple intranasal administration of PU.1 siRNA helped reduce TARC secretion and the associated infiltration of white blood cells into the bronchioles, effectively reducing the extent of inflammation in the lungs.

These results highlight the importance of PU.1 in inflammatory processes and immune diseases and could pave the way to novel treatments. “I find it encouraging that we were able to report both basic research on genes as well as an applied approach that could lead to treatment for hyperimmune responses, such as contact hypersensitivity and asthma,” comments Prof. Nishiyama.

Hopefully, further research would help clarify the regulatory and transcriptional pathways of CCL17 even more, leading to a more comprehensive understanding of the complex panorama of immune diseases.

***

Reference

Authors: Naoto Ito (1), Fumiya Sakata (1), Masakazu Hachisu (1), Kazuki Nagata (1), Tomoka Ito (1), Kurumi Nomura (1), Masanori Nagaoka (1), Keito Inaba (1), Mutsuko Hara (2), Nobuhiro Nakano (2), Tadaaki Nakajima (1), Takuya Yashiro (1), and Chiharu Nishiyama (1).

Title of original paper: The Ccl17 gene encoding TARC is synergistically transactivated by PU.1 and IRF4 driven by the mammalian common promoter in dendritic cells

Journal: Allergy
DOI: https://doi.org/10.1111/all.15184

Scientists have developed a polymer-based hydrogel that can prevent pancreatic fistulae, a frequent complication of pancreatic surgery.

An unnatural connection between the pancreas and adjacent organs, called a pancreatic fistula, is a common complication of pancreatic surgery. This condition can lead to infection, sepsis and in some cases be fatal. So far, there are no effective methods that can stop these fistulae from developing after surgery. But, now, a team led by researchers from Tokyo University of Science have developed a novel hydrogel that can prevent pancreatic fistulae and thus, save lives.

Pancreatic fistulae, or ducts that grow from the pancreas to nearby organs such as the colon, are a frequent complication after pancreatic surgery. Studies have shown that the risk of pancreatic fistulae after surgery is as high as 50%. These fistulae cause a leakage of pancreatic fluid, which can then accumulate near the pancreas and form an abscess, become severely infected, and—in severe cases—lead to death. Repairing these fistulae is also a prolonged and complex process. They say prevention is better than cure, but despite multiple attempts, there are currently no effective prevention methods for pancreatic fistulae.

In a recent study, a team of scientists—including Professor Takehisa Hanawa, Dr. Yayoi Kawano and Mr. Hiroshi Mamada from Tokyo University of Science, as well as Dr. Akira Kemmochi and Dr. Takafumi Tamura from the University of Tsukuba—have developed a novel hydrogel that can prevent the formation of these postoperative pancreatic fistulae. The study was published in Polymers for Advanced Technologies.

“There are many polymers with chemical or biological synthesis, but their preparation and application can be somewhat complicated. Our research was inspired by a desire to develop a hydrogel that can be used simply and effectively in surgical settings as one of the ‘Patient-Friendly Formulations,’” says Prof. Hanawa.

Like the name suggests, hydrogels are three-dimensional polymer networks that can hold a large amount of water. This makes them useful in a wide variety of fields, from agriculture to wound healing in medicine. These hydrogels can be prepared in one of two ways. One, using chemical techniques such as chemical reactions or electron beam crosslinking, and the other using physical methods such as the freezing-thawing (F/T) cycle method. The polymer solution is prepared and then frozen, which makes the water present in the solution gather as ice. This allows the hydrogel particles to link together. The solution is then thawed and frozen again until the desired level of linkage is achieved in the hydrogel.

In this study, the research team prepared two polyvinyl alcohol (PVA) hydrogels using of two types of PVAs, Poval® and Exceval®. They then studied then evaluated a critical hydrogel property called swelling behavior. Hydrogels absorb water, which makes them swell. This swelling can at times cause the hydrogel to rupture. They found that the Exceval® hydrogel showed a lower swelling degree, increased elasticity, and superior gel strength to the one made with Poval®. These properties implied that the Exceval® could potentially be used in the abdominal cavity after pancreatic surgery.

The research team then prepared hydrogels that contained tartrazine, a common dye used to study the drug-release behavior of hydrogels, and nefamostat mesylate (NM), a drug that is used to treat pancreatitis. They found that the drug-release behavior of both hydrogels depended on the number of F/T cycles used in their preparation.

Finally, the research team tested the hydrogel in vivo in a pancreatic fistula rat model. They found that rats with the hydrogel showed lower levels of pancreatic enzymes in the blood and abdominal fluid, indicating that the leakage of pancreatic fluid was controlled. They inferred that the hydrogel was capable of absorbing pancreatic juices and intra-abdominal fluid, and of preventing pancreatic fistula.

The research team mentions that the results of animal experiments using the gel prepared in this study have been published in the Journal of Hepato-Biliary-Pancreatic Sciences.

“Since the hydrogel prepared in this study also has the ability to absorb liquid, we believe that it can be applied, not only to the body, but also to cancerous skin ulcers and wounds, where it can absorb secretions and release medicines for treatment,” explains Prof. Hanawa.

With its adjustable properties, excellent swelling behavior and high absorption abilities, the novel Exceval® hydrogel shows great promise for clinical applications for the prevention of pancreatic fistulae.

***

Reference
Title of original paper: Development and evaluation of novel hydrogel for preventing postoperative pancreatic fistula
Journal: Polymers for Advanced Technologies
DOI: https://doi.org/10.1002/pat.5496

Long-range magnetic order has been observed in quasicrystals, strange solids that show forbidden crystal symmetries, for the first time

Since the discovery of quasicrystals (QCs), solids that mimic crystals in their long-range order but lack periodicity, scientists have sought physical properties related to their peculiar structure. Now, an international group of researchers led by Tokyo University of Science, Japan, report for the first time a long-range magnetic order in QCs with icosahedral symmetry that turn ferromagnetic below certain temperatures. This groundbreaking discovery opens doors to future research on these exotic materials.

In 1984, a routine examination of an aluminum-manganese alloy revealed a curious anomaly that was previously thought to be crystallographically impossible– a five-fold rotational symmetry. This was the discovery (later recognized by Nobel Prize) of a “quasicrystal” (QC), a curious solid that shows long-range ordering similar to crystals but lacks their periodicity. Rather, the order is “quasiperiodic,” which leads to some exotic symmetries absent in crystals. Ever since then, QCs have been the subject of enormous scientific interest.

But their potential applications remain uncertain since no physical property signifying their long-range quasiperiodic order, such as long-range magnetic order, has been observed. Until now, that is.

In a new study published in the Journal of the American Chemical Society, a global team of scientists led by Professor Ryuji Tamura of Tokyo University of Science (TUS), Japan, Professor Taku J. Sato of Tohoku University, Japan, and Professor Maxim Avdeev of the Australian Nuclear Science and Technology Organisation and University of Sydney, Australia, have reported the first-ever observation of long-range ferromagnetic order in icosahedral quasicrystals (i QCs or QCs with 5-fold rotational symmetry). Ms. Asuka Ishikawa and Dr. Shintaro Suzuki, members of the Tamura Laboratory at TUS, also made invaluable contributions to the project.

“This successful synthesis of ferromagnetic i QCs is the culmination of more than 10 years of research in our laboratory,” says Prof. Tamura, “Nobody knows what kind of peculiar behavior they will further reveal or how they can be exploited for the advancement of technology, but now we have finally taken the first step. Elucidating the properties of these ferromagnetic QCs will contribute greatly to the development of science.”

There are four major types of magnetic order: ferromagnetism, antiferromagnetism, paramagnetism, and diamagnetism. The discovery of antiferromagnetic and ferromagnetic transitions in approximant crystals (APs)—crystals with a somewhat similar structure to the related QCs that can be studied using conventional techniques—inspired the research group to look for magnetically ordered i QCs. For their research, the team prepared alloys of gold (Au), gallium (Ga) and gadolinium (Gd) and gold, gallium, and terbium (Tb). Using conventional X-ray diffraction, they observed the formation of an icosahedral quasicrystal phase for both Au-Ga-Gd and Au-Ga-Tb.

They then investigated the properties of the two i QCs using magnetic susceptibility and specific heat measurements. They found that both alloys showed a ferromagnetic phase transition at 23 K (Gd i QC) and 16 K (Tb i QC), a signature of long-range magnetic order. To further validate these results, they performed neutron diffraction experiments using ECHIDNA (ANSTO, Australia) and ISSP-GPTAS (JRR-3, Japan), and looked at the neutron diffraction patterns of the i QCs at different temperatures. They observed prominent Bragg peaks below their respective transition temperatures, confirming the ferromagnetic nature of the i QCs.

Attempts to synthesize magnetic i QCs until now have all ended in “spin-glass-like freezing,” characterized by a disordered magnetic state. Against this backdrop, the discovery of long-range ferromagnetic order in this study has consequences far beyond the landscape of the physical properties of materials and opens doors to tailored magnetic materials. “The crystal symmetry of ferromagnetic QCs is much higher than that of conventional periodic crystals, which makes it possible to apply them as ultrasoft magnetic materials,” says Prof. Tamura.

With the decades-long quest for long-range magnetic order in i QCs finally at an end, the world is now eagerly waiting to see what this groundbreaking discovery entails. With such superlative research pioneering the way, it won’t be long before we find out!

Japanese researchers have succeeded in effective intranasal delivery of modified anti-depressant peptide-based drug to the brain

Drug delivery to the brain has been challenging, owing to disadvantages like systemic absorption, slow axonal transportation, rapid drug degradation, and invasiveness of commonly used techniques. Accordingly, researchers from Japan have successfully attempted to bolster intranasal drug delivery to the brain, making it as effective as other conventional delivery methods, by adding sequences that enhance cell permeability and degradation escape to an anti-depressant drug called glucagon-like peptide 2. Their findings are published in the Journal of Controlled Release.

Clinical researchers working on drug delivery to the brain have been faced with several challenges. Firstly, currently used methods like intracerebroventricular (ICV) administration are extremely invasive. Secondly, other methods like intranasal administration are weighed down by with issues like ineffective cell permeability. Thirdly, even if the drugs gain access into the neurons, their action in the brain is impeded by slow axonal transportation and fast degradation.

After years of meticulous research, a group of Japanese researchers, led by Prof. Chikamasa Yamashita from Tokyo University of Science, working on intranasal drug delivery (IDD) to the brain, have finally achieved success in delivering an anti-depressant drug called glucagon-like peptide 2 (GLP-2) in a mouse model of depression. They modified the drug to accelerate its transportation, while minimizing any degradation, all while achieving the same therapeutic effect as ICV administration, according to their findings published as a research article in the Journal of Controlled Release.

Speaking about the motivation behind pursuing IDD, Prof. Yamashita, the corresponding author of the study, says, “Although there have been more than 20 years of phenomenal IDD research, I had wondered why it has not been put to practical use. Then, I realized that most IDD research had focused on drug delivery through the olfactory epithelium, which accounts for only 2% of human nasal mucosa. Alternatively, my team focused on the central delivery of drugs through the remaining 98% of such mucosa – respiratory epithelium, specifically through the trigeminal nerve.”

The scientists began work with GLP-2, a neuropeptide that has shown therapeutic effects, even in treatment-resistant depression. Given that many drugs entering the body lose their therapeutic effectiveness due to endosomal degradation within the cells, the scientists added a peptide-derived sequence to GLP-2, called a penetration accelerating sequence (PAS) to help evade this degradation. Also, they enhanced the permeability of the drug to the respiratory epithelium, by the addition of another membrane-permeability promoting peptide-derived sequence called as cell penetrating peptides (CPP). Then, they proceeded to test this modified drug in the mouse model of depression.

Their results showed that GLP-2 uptake into the respiratory epithelial cells were enhanced owing to the presence of the CPP. GLP-2 endosomal escape was also enhanced by PAS. In short, this double-modification allowed the effective nose-to-brain delivery of GLP-2. Interestingly, the researchers found that the modified IDDS achieved therapeutic effectiveness in 20 minutes, similar to ICV administration. However, IV administration didn’t demonstrate the intended effect.

Overall, this breakthrough study has taken medicine one step closer to the practical application of intranasal neurological drug administration. Dr. Tomomi Akita, another lead scientist involved in the study, adds, “We hope that our results can be replicated in humans, in the near future. Our study possibly paves the way for futuristic brain delivery applications like nanobiotechnology, and adult genetic engineering, too.”

What a time for neuro-pharmaceutical research, indeed!

Reference

Titles of original papers: Usefulness of cell-penetrating peptides and penetration accelerating sequence for nose-to-brain delivery of glucagon-like peptide-2

Journal: Journal of Controlled Release

DOI: https://doi.org/10.1016/j.jconrel.2021.06.007

Researchers identify a novel regulatory axis targeting dendritic cell activity and subsequent inflammatory responses in immune disorders

While dendritic cell immunoreceptor (DCIR) is known to mediate inflammation and bone metabolism, ligands that bind DCIR and the mechanisms underlying DCIR activity remain poorly understood. Researchers from Japan have now identified “asialo-biantennary N-glycan”—a glycoprotein present on the surface of bone cells and dendritic cells, as a functional ligand of DCIR. Their findings could help in understanding DCIR’s role in the pathogenesis of autoimmune diseases and bone disorders and develop novel targeted therapies.

Immune cells play a key role in mediating inflammatory responses. Dysregulation in signaling mechanisms that operate across immune cells can trigger chronic inflammatory diseases like rheumatoid arthritis that cause pain and swelling in joints. One such immune cell known to be involved in autoimmune diseases is the dendritic cell. The activity of dendritic cells is regulated by the dendritic cell immunoreceptor (DCIR) present on their surface, which comprises a carbohydrate recognition domain that can bind to sugar moieties present on other proteins or cell surfaces, in a calcium dependent manner. The activity of osteoclast, which is involved in bone degradation, is also regulated by DCIR. However, little is known about the interacting partners of DCIR that help mediate inflammatory responses.

A team of researchers from Japan led by Professor Yoichiro Iwakura of the Department of Experimental Animal Science at the Research Institute for Biomedical Sciences, Tokyo University of Science, have now delved deeper into understanding the mechanisms underlying DCIR activity. In their previous work, the researchers reported that mice deficient in DCIR spontaneously develop arthritis and metabolic bone disorders. Building on this finding, in a recent study published in the Journal of Experimental Medicine, they sought to elucidate DCIR binding partners and immune signaling mechanisms involved in inflammatory diseases. “In this study, we have identified a novel functional ligand of DCIR, likely involved in the pathogenesis of arthritis and other autoimmune diseases like multiple sclerosis. We are hopeful that our work can advance the research of immunology and glycobiology in inflammatory diseases.”, explains Prof. Iwakura.

The researchers began by identifying potential ligands (molecules that bind to cell receptors) of DCIR on immune and bone cells, and found that DCIR binds to glycoproteins present on the surface of macrophages and osteoclasts, the latter differentiating from bone marrow derived macrophages (BMMs), and involved in bone degeneration and remodeling. On further characterization of the glycoprotein, they noted that this interaction was specific to “asialo-biantennary N-glycan (NA2),” a complex carbohydrate moiety comprising various sugar molecules.

Having identified the DCIR ligand, the team next sought to understand the effect of DCIR on osteoclast differentiation and “osteoclastogenesis,” a process contributing to bone loss. Interestingly, cells deficient in DCIR showed a significant increase in the expression of osteoclastogenesis associated genes. As the researchers speculated, expression of DCIR significantly suppressed the differentiation of osteoclasts, thus suggesting DCIR as an independent inhibitor of osteoclastogenesis. Further confirming this finding, a mutant version of DCIR, incapable of recognizing carbohydrate residues, was shown to not exhibit this inhibitory effect.

The role of DCIR in osteoclast differentiation, and its interacting ligand, NA2, now decoded, the team next examined the effect of NA2 on osteoclastogenesis. Consistent with their previous finding, NA2 treatment suppressed the differentiation of osteoclasts from wild-type BMMs but not from cells deficient in DCIR, underscoring the role of NA2 as a specific functional ligand of DCIR that suppresses osteoclastogenesis.

Taking a step further, the researchers treated mouse autoimmune disease models with neuraminidase, an enzyme that removes terminal “sialic acid” residues from N-glycan, thereby enhancing the exposure of NA2. Much to their delight, neuraminidase treatment further suppressed autoimmune diseases like autoimmune arthritis or experimental autoimmune encephalomyelitis, yet again, in a DCIR dependent manner! Furthermore, neuraminidase treatment ameliorated inflammation and associated bone loss in a mouse model of arthritis, thereby confirming their findings in vitro and in vivo. The inhibitory effect of DCIR-NA2 interaction on autoimmune diseases was found to be mediated through suppression of the antigen presenting ability of dendritic cells and subsequent decrease in the activation of other immune cells that contribute to inflammation.

All these findings, together, highlight a novel regulatory mechanism of DCIR signaling involved in the suppression of autoimmunity and excess bone loss. Commenting on the clinical applications of their work, Prof. Iwakura observes, “Our findings are expected to contribute to the understanding of the pathogenesis of human autoimmune diseases such as rheumatoid arthritis and to the development of novel therapies for the treatment of immune and bone metabolic diseases.”

This study indeed takes us a step closer to resolving the complex immune mechanisms of autoimmune diseases, thus paving the way towards effective and targeted treatments.

Using a photocatalyst, scientists have identified the factors behind racemization process of chiral sulfoxides

Chiral sulfoxides, molecules that contain sulfur centers that cannot be superimposed on their mirror images, have wide applications in the chemical industry. This ‘chirality’ of the molecules can make them extremely selective during reactions, which makes them valuable, especially in the pharmaceutical industry. But sulfoxides are famously stable, making their conversion into the desired mirror image challenging. Now, scientists from Tokyo University of Science have developed a new method to convert sulfoxides using light.

The first place you need to look to understand “chirality” are your hands – identical structures that cannot be successfully superimposed over one another. Like our hands, many molecules also exhibit chirality. Different forms of chiral molecules (like the right and left hand) are called enantiomers. Chirality is of particular importance in biology because it endows biological reactions with a high specificity. The reactions that one enantiomer take part in may not necessarily be ones that the other can interact in. This makes enantiomers, and the production of enantiomers, highly desirable to the pharmaceutical industry.

In a solution, enantiomers convert automatically into their mirror-image version by a process called “racemization.” Manipulating the racemization reaction helps produce the desired enantiomer as a product. But some molecules, such as sulfoxides, undergo racemization very slowly. Recently, a team of scientists from Japan—including Professor Hideyo Takahashi, Assistant Professor Kosho Makino, Ms. Kumi Tozawa, and Ms. Yuki Tanaka from Tokyo University of Science—has developed a method to achieve the rapid racemization of chiral sulfoxides, an important group of bioactive compounds and intermediates in chemical reactions. This study has been published in the Journal of Organic Chemistry.

One of the challenges in the racemization of chiral sulfoxides is the requirement of very high temperature (about 200°C) to invert the sulfur-centered pyramid-shaped structure of sulfoxides. But previous research had shown that the racemization of chiral sulfoxides by using light, i.e., photoirradiation, was also possible. This was achieved using a “photosensitizer,” a molecule that donated an electron to the reactants when irradiated with light, thus decreasing the energy required to achieve the reaction. “By conducting the reaction in the presence of a photosensitizer, we were able to achieve the racemization of chiral sulfoxide in much more moderate conditions,” says Prof. Takahashi.

For their work, the team photoirradiated several sulfoxides in the presence of the photosensitizing molecule 2,4,6-triphenylpyrylium tetrafluoroborate (TPT+) and found that effective racemization of a number of different sulfoxides occurred very quickly. Finally, they investigated the kinetics of these reactions and hypothesized a reaction mechanism by which they occurred.

Interestingly, the researchers noticed that not all sulfoxides were racemized by TPT. Certain functional groups such as dimethylamino, pyrrolidyl, and anisyloxy on the sulfoxide hindered the racemization process. To find out why, they assessed the electrochemical potentials (a measure of reactivity) of these functional groups by “cyclic voltammetry.” They saw that these functional groups had lower electrochemical potentials than sulfoxide, implying that they reacted ahead of the sulfoxides, thereby preventing their racemization. “It is our belief that determining electrochemical potentials via cyclic voltammetry will help determine the reactive nature of a photochemical reaction, which will save valuable experimentation and research time,” says Prof. Takahashi.

The study emerges as a distinguished addition to research on manipulating the chirality of molecules. As per Prof. Takahashi, “Our photosensitization-based rapid racemization technology can be used for dynamic asymmetric-induced reactions for obtaining the desired enantiomers.”

Indeed, such research is sure to advance the field of chiral active pharmaceuticals and functional materials!

Reference
Titles of original papers: Rapid photoracemization of chiral alkyl aryl sulfoxides
Journal: Journal of Organic Chemistry
DOI: https://doi.org//10.1021/acs.joc.1c02320

Scientists develop a tool that uses machine learning and a dynamical systems-based approach to identify a precursor of combustion instability in engines

Combustion engines, like those in aircrafts, remain at risk of fatal damage by a phenomenon called “combustion oscillations,” where pressure fluctuations inside the engine become large. Now, researchers from Japan have developed a novel tool to detect a precursor to combustion oscillations using machine learning and a dynamical systems-based approach, opening doors to the prediction and prevention of related fatal damage to engines.

Combustion engines have been around since the late 18th century, although they did not gain popularity until over 50 years later. Now, they are practically ubiquitous, powering anything from cars and airplanes to turbines.

The part of the combustion engine in which the fuel is burnt (in the presence of oxygen) is called the combustor. The lifespan of a combustor can be limited by a phenomenon called “thermoacoustic combustion oscillations.” When thermoacoustic oscillations become too large or out of control, it causes fatal damage to combustors, which can have enormous financial and human consequences.

Detecting combustion oscillations and preventing damage is a key effort in the field of thermal engineering. Recently, a team of scientists from Japan—including Hiroshi Gotoda, Yuhei Shinichi, and Naohiro Takeda from Tokyo University of Science, as well as Seiji Yoshida and Takeshi Shoji from the Japan Aerospace Exploration Agency (JAXA)—have developed a promising tool for the detection of a precursor of thermoacoustic oscillations. The study was made available online on May 10, 2021 and published in volume 59 of the American Institute of Aeronautics and Astronautics Journal on October 1, 2021.

“In our study, we have shown that the methodology combining dynamical systems theory and machine learning can be useful for detecting predictive combustion oscillations in multisector combustors, such as those in aircraft engines,” says Prof. Gotoda, who headed the study.

The team conducted combustion experiments with varying fuel flow rates in a staged multisector combustor developed by JAXA.

The scientists used the data from these experiments to train a machine learning algorithm called ‘support vector machine (SVM).’ The SVM allowed them to classify the combustion into three states—stable, transitional, and combustion oscillations. The pressure fluctuations in the transitional state are key to predicting future combustion oscillations. In the transitional state, pressure fluctuations transition from being small-amplitude and aperiodic to being large-amplitude and periodic. Amplitude represents the ‘largeness’ of the fluctuation, whereas periodicity describes the repetition of the fluctuation.

“The findings of this study will contribute greatly towards developing a method to detect combustion oscillations in advance in aircraft engines,” reveals Prof. Gotoda.

These findings could have far-reaching consequences, paving the way for confident and timely predictions of combustion oscillations, with the potential to save billions of dollars and human lives.