Tag: Japan

Researchers find that rose essential oil activates tomato defense genes and attracts herbivore predators that protect the plants.

Following injury, plants release terpenoids to enhance their defenses. Researchers at the Tokyo University of Science studying terpenoid-enriched essential oils (EOs) have found that rose EO (REO) can stimulate defense genes in tomato leaves. Furthermore, REO attracts herbivores that protect the plant from the moth species, Spodoptera litura, and Tetranychus urticae, a mite pest. This suggests that applying REO could be a sustainable approach to pest management in organic farming.

Plants-derived essential oils (EOs) find applications in various industries, such as detergents, cosmetics, pharmacology, and food additives. Moreover, EOs have an exceptional safety profile, and their numerous bioactivities greatly benefit human health. Beyond these benefits, EOs have also been found to illicit insect-repellent responses by inducing neurotoxic effects.

Terpenoids are abundant in plant EOs and have garnered widespread attention as they can regulate plant defense responses by regulating the expression of defense genes. For example, soybean and komatsuna plants, when grown near mint, experience a significant improvement in defense properties and become resistant to herbivores. This phenomenon occurs through a process known as “eavesdropping,” wherein volatile compounds are released from the mint plant. These volatile compounds trigger the activation of defense genes, protecting against potential herbivore threats.

Today, applying chemical pesticides is the method of choice for crop protection, but the damage they cause to the environment and ecosystems, along with the need to increase food productivity, stresses the need for safer alternatives. Thus, there is an urgent need for investigation of plant defense potentiators. In this regard, the availability of EOs makes them attractive candidates as environmentally friendly plant defense activators. However, there is a lack of sufficient proven examples to meet the demand.

To address this, a research team led by Professor Gen-ichiro Arimura from the Department of Biological Science and Technology at the Tokyo University of Science (TUS) assessed the efficacy of 11 EOs in activating tomato defense responses. “EOs used as fragrances for various purposes contain odor components, which may have the ability to work like volatile compounds in conferring pest resistance. We aimed to investigate the effects of these EOs on plants’ insect pest resistance,” says Prof. Arimura. The team’s findings were published in the Journal of Agricultural and Food Chemistry on March 18, 2024.

The team profiled the effects of terpenoid-enriched EOs on tomato plants. They applied ethanol-diluted solutions of 11 different EOs to the soil of potted tomato plants, performed molecular analyses to study the gene expression inside leaf tissue, and observed that rose EO (REO) increased the transcript levels of PIR1 and PIN2, the genes involved in plant defense. Additionally, tomato plants treated with REO exhibited reduced leaf damage caused by the Spodoptera litura (a moth species) larvae and Tetranychus urticae (a mite pest). Furthermore, to explore the possibility of broader application, the researchers conducted a field experiment to measure REO activity in field conditions. They observed a 45.5% reduction in tomato pest damage compared to the control solution. The researchers believe that REO could serve as a viable alternative to pesticides during the winter and spring seasons when pest infestation is less severe and could potentially reduce pesticide usage by almost 50% during summers.

Explaining the research findings, Prof. Arimura says, “REO is rich in β-citronellol, a recognized insect repellent, which enhances REO’s efficacy. Owing to this, damage caused by the moth larvae and mites was significantly minimized, confirming REO as an effective biostimulant. The findings also showed that a low concentration of REO did not repel T. urticae but attracted Phytoseiulus persimilis, a predator of these spider mites, thus exhibiting a dual function of REO.”

Overall, the study highlights the role of β-citronellol-enriched EO in activating defense genes in tomato leaves. Additionally, it provides evidence that REO is an effective biostimulant for enhancing plant defense against pests, which is also safe as it does not lead to phytotoxicity or leave any toxic residues behind. “Our study suggests a practical approach to promoting organic tomato production that encourages environmentally friendly and sustainable practices. This research may open doors for new organic farming systems. The dawn of potent environmentally friendly and natural pesticides is upon us,” concludes Prof. Arimura.

Artificial intelligence (AI) is known for its high energy consumption, especially in data-intensive tasks like health monitoring. To address this, researchers at Tokyo University of Science (TUS) have developed a flexible paper-based sensor composed of nanocellulose and zinc oxide (ZnO) nanoparticles that operates like the human eyes and brain. The sensor is energy-efficient, responds to optical input in real-time, and is both flexible and easy to dispose of, making it ideal for health monitoring applications.

A paper-based sensor based on the operation of the human brain paves the way for standalone energy-efficient AI-based health monitoring devices

From creating images, generating text, and enabling self-driving cars, the potential uses of artificial intelligence (AI) are vast and transformative. However, all this capability comes at a very high energy cost. For instance, estimates indicate that training OPEN AI’s popular GPT-3 model consumed over 1,287 MWh, enough to supply an average U.S. household for 120 years. This energy cost poses a substantial roadblock, particularly for using AI in large-scale applications like health monitoring where large amounts of critical health information are sent to centralized data centers for processing. This not only consumes a lot of energy but also raises concerns about sustainability, bandwidth overload, and communication delays.

Achieving AI-based health monitoring and biological diagnosis requires a standalone sensor that operates independently without the need for constant connection to a central server. At the same time, the sensor must have a low power consumption for prolonged use, should be capable of handling the rapidly changing biological signals for real-time monitoring, be flexible enough to attach comfortably to the human body, and be easy to make and dispose of due to the need for frequent replacements for hygiene reasons.

Considering these criteria, researchers from Tokyo University of Science (TUS) led by Associate Professor Takashi Ikuno have developed a flexible paper-based sensor that operates like the human brain. Their findings were published online in the journal Advanced Electronic Materials on 22 February 2024.

“A paper-based optoelectronic synaptic device composed of nanocellulose and ZnO was developed for realizing physical reservoir computing. This device exhibits synaptic behavior and cognitive tasks at a suitable timescale for health monitoring,” says Dr. Ikuno.

In the human brain, information travels between networks of neurons through synapses. Each neuron can process information on its own, enabling the brain to handle multiple tasks at the same time. This ability for parallel processing makes the brain much more efficient compared to traditional computing systems. To mimic this capability, the researchers fabricated a photo-electronic artificial synapse device composed of gold electrodes on top of a 10 µm transparent film consisting of zinc oxide (ZnO) nanoparticles and cellulose nanofibers (CNFs).

The transparent film serves three main purposes. Firstly, it allows light to pass through, enabling it to handle optical input signals representing various biological information. Secondly, the cellulose nanofibers impart flexibility and can be easily disposed of by incineration. Thirdly, the ZnO nanoparticles are photoresponsive and generate a photocurrent when exposed to pulsed UV light and a constant voltage. This photocurrent mimics the responses transmitted by synapsis in the human brain, enabling the device to interpret and process biological information received from optical sensors.

Notably, the film was able to distinguish 4-bit input optical pulses and generate distinct currents in response to time-series optical input, with a rapid response time on the order of subseconds. This quick response is crucial for detecting sudden changes or abnormalities in health-related signals. Furthermore, when exposed to two successive light pulses, the electrical current response was stronger for the second pulse. This behavior termed post-potentiation facilitation contributes to short-term memory processes in the brain and enhances the ability of synapses to detect and respond to familiar patterns.

To test this, the researchers converted MNIST images, a dataset of handwritten digits, into 4-bit optical pulses. They then irradiated the film with these pulses and measured the current response. Using this data as input, a neural network was able to recognize handwritten numbers with an accuracy of 88%.

Remarkably, this handwritten-digit recognition capability remained unaffected even when the device was repeatedly bent and stretched up to 1,000 times, demonstrating its ruggedness and feasibility for repeated use. “This study highlights the potential of embedding semiconductor nanoparticles in flexible CNF films for use as flexible synaptic devices for PRC,” concludes Dr. Ikuno.

Let us hope that these advancements pave the way for wearable sensors in health monitoring applications!

Quick-acting targeted therapies with minimal side effects are an urgent need for the treatment of anxiety-related disorders. While delta opioid receptor (DOP) agonists have shown ‘anxiolytic’ or anxiety-reducing effects, their mechanism of action is not well-understood. A new study by researchers from Tokyo University of Science highlights the role of specific neuronal circuits in the brain involved in the development of anxiety, and distinct mechanisms of action of the therapeutic DOP agonist – KNT-127.

Anxiety-related disorders can have a profound impact on the mental health and quality of life of affected individuals. Understanding the neural circuits and molecular mechanisms that trigger anxiety can aid in the development of effective targeted pharmacological treatments. Delta opioid receptors (DOP), which localize in the regions of the brain associated with emotional regulation, play a key role in the development of anxiety. Several studies have demonstrated the therapeutic effects of DOP agonists (synthetic compounds which selectively bind to DOPs and mimic the effect of the natural binding compound) in a wide range of behavioral disorders. One such selective DOP agonist—KNT-127—has been shown to exert ‘anxiolytic’ or anxiety-reducing effects in animal models, with minimal side effects. However, its mechanism of action is not clearly understood, thereby limiting its widespread clinical application.

To bridge this gap, Professor Akiyoshi Saitoh, along with Ms. Ayako Kawaminami and team from the Tokyo University of Science, Japan, conducted a series of experiments and behavioral studies in mice. Explaining the rationale behind their work, Prof. Saitoh says, “There are currently no therapeutic drugs mediated by delta opioid receptors (DOPs). DOPs likely exert anti-depressant and anti-anxiety effects through a mechanism of action different from that of existing psychotropic drugs. DOP agonists may, therefore, be useful for treatment-resistant and intractable mental illnesses which do not respond to existing treatments.” Their study was published on 29 December 2024, in Neuropsychopharmacology Reports,

The neuronal network projecting from the ‘prelimbic cortex’ (PL) of the brain to the ‘basolateral nucleus of the amygdala’ (BLA) region, has been implicated in the development of depression and anxiety-like symptoms. The research team has previously shown that KNT-127 inhibits the release of glutamate (a key neurotransmitter) in the PL region. Based on this, they hypothesized that DOP activation by KNT-127 suppresses glutamatergic transmission and attenuates PL-BLA-mediated anxiety-like behavior. To test this hypothesis, they developed an ‘optogenetic’ mouse model wherein they implanted a light-responsive chip in the PL-BLA region of mice and activated the neural circuit using light stimulation. Further, they went on to assess the role of PL-BLA activation on innate and conditioned anxiety-like behavior.

They used the elevated-plus maze (EPM) test, which consists of two open arms and two closed arms on opposite sides of a central open field, to assess behavioral anxiety in the mice. Notably, mice with PL-BLA activation spent lesser time in the central region and open arms of the maze, compared to controls, which was consistent with innate anxiety-like behavior. Next, the researchers assessed conditioned fear response of the animals by exposing them to foot shocks and placing them in the same shock chamber the following day without re-exposing them to current. They recorded the freezing response of the animals which reflects fear. Notably, animals with PL-BLA activation and controls exhibited similar behavior, suggesting that distinct neural pathways control innate anxiety-like behavior and conditioned fear response.

Finally, they examined the effects or KNT-127 treatment on anxiety-like behavior of mice using the EPM test. Remarkably, animals treated with KNT-127 exhibited an increase in the percentage time spent in the open arms and central field of the maze, compared to controls. These findings suggest that KNT-27 reduces anxiety-like behavior induced by the specific activation of the PL-BLA pathway.

Overall, the study reveals the role of the PL-BLA neuronal axis in the regulation of innate anxiety, and its potential function in DOP-mediated anxiolytic effects. Further studies are needed to understand the precise underlying molecular and neuronal mechanisms, for the development of novel therapies targeting DOP in the PL-BLA pathway.

Highlighting the long-term clinical applications of their work, Prof. Saitoh remarks, “The brain neural circuits focused on in this study are conserved in humans, and research on human brain imaging has revealed that the PL-BLA region is overactive in patients with depression and anxiety disorders. We are optimistic that suppressing overactivity in this brain region using DOP-targeted therapies can exert significant anxiolytic effects in humans.”

Merrillianin is a naturally occurring compound found in Chinese herbal medicine. In a significant milestone for drug development, researchers have succeeded in its artificial synthesis, with the potential for helping treat nervous system diseases. The compound, previously tricky to synthesize due to its complex chemical structure, was successfully produced using 30 reactions. This breakthrough paves the way for the commercial development of drugs targeting diseases such as rheumatism and neuralgia.

An avenue that scientists are currently exploring for the development of novel pharmaceuticals involves the synthesis of bioactive compounds found in Chinese herbal medicine. This collaborative effort, combining traditional knowledge with modern scientific methods, focuses on pharmaceutically relevant compounds found in medicinal plants for large-scale synthesis. An important compound in this context is merrillianin, a type of illicium sesquiterpene that was isolated in 2002 from the fruit of Illicium merrillianum, a plant that belongs to the same genus as star anise. Illicium sesquiterpenes are naturally occurring compounds which hold promise for treating nervous system diseases. However, merrillianin has a complex structure with a central arrangement of six consecutive stereogenic carbon centers, including three quaternary carbon stereogenic centers, and three rings fused to two carbons. This complexity has posed challenges for the artificial synthesis of merrillianin, leading to limited progress in its practical application since its isolation.

In a breakthrough study published in the journal Organic Letters on 31 December 2023, a research group led by Assistant Professor Takatsugu Murata and Professor Isamu Shiina from Tokyo University of Science (TUS) succeeded in synthesizing merrillianin, opening doors to its artificial synthesis almost 20 years after the compound was isolated.

“Illicium sesquiterpenes are a group of compounds that are expected to be effective against neurological diseases, but their highly oxidized and ring-fused structures have made it difficult to synthesize them artificially. However, we have synthetic technique and knowledge about the synthesis of highly complicated compounds such as taxol,” says Dr. Murata. “Therefore, we wanted to perform the world’s first artificial synthesis of merrillianin, which is expected to have anti-rheumatic activity, and create a lead compound that can contribute to the treatment of neurological diseases.”

Merrillianin can be obtained with yields as high as 80% via the Wacker-type oxidation of a dilatone. However, the challenge lies in efficiently preparing the precursor compounds for the dilatone. To address this, the researchers employed a total of 30 reaction steps, covering the synthesis of precursors to the final production of merrillianin. The process commences with the Mukaiyama aldol reaction, which involves enol silyl ether and acetaldehyde. This reaction leads to the creation of a dithioacetal, a compound that includes a quaternary carbon stereogenic center. Subsequently, the dithioacetal undergoes a series of reactions with an iodo compound, resulting in the formation of α, β-unsaturated ester possessing an aldol structure. The next steps involve a reductive intramolecular cyclization of this compound to cyclopentane, followed by an intramolecular Michael’s reaction for the formation of tricyclic dilactone with a total yield of 1.6%. Tricyclic dilactone is a key intermediate for the commercial production of a wide variety of Illicium sesquiterpene compounds, including merrillianin.

The researchers point out that if merrillianin has high bioactivity, the amount required for treatment would be very little. (According to the isolation report, 3 mg of merrillianin was isolated from 30 kg of fruit.) Interestingly, it would be possible to examine its bioactivity using the synthetic version prepared by the group.

The synthesis method also revealed the absolute configuration of merrillianin, which, so far, had only known relative configurations. The proposed synthesis method for merrillianin represents another milestone for the research group, which previously succeeded in synthesizing the naturally occurring tanzawaic acid B found in the fungus Penicillium citrinum that has the potential for developing antibiotics against multidrug-resistant bacteria.

The research group’s ongoing dedication to synthesizing compounds with interesting biological activities holds promise for future discoveries in the field of drug development. Species of the Illicium genus have been used as medicinal herbs for the treatment of conditions like rheumatoid arthritis and traumatic injuries, and the synthesis of merrillianin could also contribute to advancements in these areas. “The proposed synthesis method for merrillianin will help develop suitable drugs to treat nervous system diseases such as rheumatism, and neuralgia, improving neurological disease prognosis and enhancing patient quality of life,” concludes Prof. Shiina.

Dibenzothiophene S-oxides are important in various biochemical processes. However, their synthesis using conventional methods is not easy. Researchers from Tokyo University of Science have now developed an innovative two-step process involving a Suzuki–Miyaura coupling of 2-bromoaryl-substituted sulfinate esters, followed by intramolecular electrophilic sulfinylation. This method can facilitate the facile synthesis of polysubstituted dibenzothiophene oxides without damaging highly reactive functional groups. The resulting compounds can find applications in fields like drug development and biochemical research.

Organic compounds in the field of chemistry range from simple hydrocarbons to complex molecules, with diverse functional groups added to the main carbon backbone. These functional groups impart the compounds distinct chemical properties as well as participate in various chemical transformations, making them important precursors for the synthesis of diverse compounds. Scientists have, therefore, actively engaged in creating molecules that feature novel and highly reactive functional groups.

One such class of compounds are dibenzothiophenes and their derivatives containing S-oxide or S,S-dioxide moieties (sulfur atoms bonded to one and two oxygen atoms respectively). These compounds are of special interest in the fields of pharmaceutical sciences, materials chemistry, and chemical biology. Dibenzothiophenes consist of benzene rings fused to a thiophene ring—a five-membered ring with four carbon atoms and one sulfur atom. When dibenzothiophene S-oxides are exposed to UV light, they release atomic oxygen, which is useful for DNA cleavage and oxidation of adenosine-S’-phosphosulfate kinase, an enzyme involved in cellular processes. Additionally, the S–O bond can be activated to introduce different functional groups, enabling the creation of a wide range of molecules with diverse properties and applications. The conventional method of producing functionalized dibenzothiophene S-oxides involves thiophene ring formation followed by subsequent S-oxidation. However, this reaction is challenging to carry out.

To address this, Associate Professor Suguru Yoshida, Ms. Yukiko Kumagai, Mr. Akihiro Kobayashi, and Mr. Keisuke Nakamura from Tokyo University of Science (TUS) have developed a simple two-step method of synthesizing dibenzothiophene S-oxides. The method involves Suzuki–Miyaura coupling of 2-bromoaryl-substituted sulfinate esters, followed by an intramolecular electrophilic sulfinylation.

The details of the method, published in the journal Chemical Communications on 10 January 2024, opens possibilities for creating a variety of important sulfur-containing molecules in the life sciences that were traditionally difficult to synthesize using conventional methods.

“Dibenzothiophene oxides are attracting attention in the field of chemical biology, and several researchers have developed a reaction using dibenzothiophene oxide, which can now be synthesized using this method. We expect this research to elucidate life phenomena involving reactive oxygen species,” explains Dr. Yoshida, while talking about this study.

The Suzuki–Miyaura coupling is a widely used organic reaction between boronic acids and organic halides, leading to the formation of a new carbon–carbon bond. In the proposed method, sulfinate esters react first with arylboronic acids in the presence of a palladium catalyst. Next, the intermediate biaryl compounds are activated with Tf2O, leading to subsequent cyclization by electrophilic activation.

Compared to the conventional oxidation method of synthesizing dibenzothiophene, this innovative approach developed by Dr. Yoshida and his team can accommodate a wide range of functional groups, including highly reactive ones, enabling the synthesis of polysubstituted dibenzothiophene oxides not achievable earlier. Using the method, the researchers synthesized dibenzothiophene oxides having an o-silylaryl triflate moiety, a compound useful as an aryne generation site, but tends to get easily damaged when produced using conventional methods. The o-silylaryl triflate moiety serves as a useful reactive intermediate and can undergo various transformations to produce highly substituted arenes. The proposed method, therefore, not only simplifies the synthesis method but also opens doors for a diverse range of dibenzothiophene S-oxides and their derivatives.

The novel method is a significant step forward in the field of chemical biology. Going ahead, the researchers anticipate that these compounds can find useful applications in diverse research areas, paving the way for innovations and discoveries. “The proposed method can enable the synthesis of polysubstituted benzothiophene oxides, which are expected to be useful in a wide range of research fields,” concludes Dr. Yoshida.

Consistent manufacturing and production of monoclonal antibodies (mAbs) is critical, and their functional profiles depend on cell culture conditions. Now, researchers from Japan have investigated the role of intracellular polyamines on N-glycan profiles of mAbs. They found that polyamine depletion led to an ER stress response in CHO cells, leading to an increase in galactosylation of mAbs. Supplementation of spermidine recovered N-glycan profiles. These findings will contribute to the stable production of antibody-based drugs.

Monoclonal antibodies (mAbs) are laboratory-designed proteins that mimic the immune system’s antibodies. To date, many therapeutic mAbs belonging to the immunoglobulin G (IgG) class of antibodies, have been approved for the treatment of cancer and autoimmune diseases. Cell lines such as the Chinese hamster ovary (CHO) cells are generally used to produce mAbs. Notably, the production and manufacture of mAbs are regulated by critical quality attributes (CQAs) to ensure their safety and efficacy in treatment.

An important CQA for mAbs is the N-linked glycosylation present at a specific position (Asn297). N-linked glycans consist of N-acetylglucosamine (GlcNAc), mannose (Man), fucose (Fuc), galactose (Gal), and sialic acid. The heterogeneity of the N-linked glycan profiles of mAbs can be attributed to the different numbers and linkages of additional saccharides. The composition of N-linked glycans affects the overall therapeutic efficacy, targeting ability, and immune-specificity of these antibodies. For example, antibody-dependent cellular cytotoxicity (ADCC) is influenced by the fucosylation and galactosylation of N-linked glycans. Complement-dependent cytotoxicity (CDC) is also affected by the galactosylation and sialylation of N-linked glycans. Hence, it’s crucial to meticulously regulate N-linked glycan profiles throughout the manufacturing process because the heterogeneity of the N-linked glycan profile of mAbs depends on the cell culture duration and changes in nucleotide sugars and glycosylation enzyme levels.

Recently, Dr. Kyohei Higashi, Associate Professor at Tokyo University of Science (TUS) in Japan, along with a team of researchers including Dr. Rin Miyajima and Dr. Masahiro Komeno, conducted a study to explore the effects of polyamines on N-linked glycan profiles of mAbs in CHO DP-12 cells. Their work was made available online on November 3, 2023 in the Journal of Biotechnology.

“Because the carbohydrate structure of mAbs changes depending on the state of the cells, we were interested in investigating the relationship between intracellular polyamines and the carbohydrate structure of mAbs from CHO cells.” explained Dr. Higashi, when asked about the motivation behind the research.

Polyamines (putrescine, PUT; spermidine, SPD; and spermine, SPM) are present in millimolar concentrations in all living organisms and play essential roles in normal cell growth and differentiation. PUT, SPD, and SPM contained two, three, and four amino groups, respectively. PUT is synthesized from ornithine (ORN) by ornithine decarboxylase (ODC), a rate-limiting enzyme in the polyamine biosynthesis pathway. SPD is synthesized from putrescine by spermidine synthase, and spermine is synthesized from spermidine by spermine synthase. Intracellular polyamine levels are regulated at various steps, including synthesis, degradation, and transport, and are affected by external stimuli, aging, and diseases. Because CHO cells lack arginase activity to produce ORN from arginine, they cannot produce polyamines in serum-free media, resulting in a decrease in intracellular polyamine levels, which causes a low growth rate and cell viability during long-term cultivation.

Intracellular polyamine levels can also be decreased by treatment with α-difluoromethylornithine (DFMO), an inhibitor of ODC. The depletion of intracellular polyamines by DFMO can be reversed by the addition of SPD to the growth media of CHO cells.

Upon introducing DFMO to the CHO cells, the team observed that IgG antibody galactosylation surged, along with an increase in the levels of β1,4-galactosyl transferase 1 (B4GALT1) mRNA. This mRNA is pivotal in governing the IgG galactosylation mechanism within CHO cells. What’s more, IgG production decreased by approximately 30% in DFMO-treated cells.

Dr. Higashi hypothesized that the decrease in IgG production was a result of endoplasmic stress (ER) stress response caused by polyamine depletion. During ER stress response, protein folding ceases, resulting in the arrest of the normal function of cells. Chaperone proteins assist in the correct folding of other protein classes and play a crucial role under both normal and stress conditions. The results of the ER stress response study confirmed the increased expression levels of chaperones for glycoprotein folding, in polyamine-depleted cells.

The team further observed that upon using tunicamycin, an ER stress inducer inhibiting N-glycosylation, ER stress from polyamine depletion triggered B4GALT1 mRNA expression, increasing IgG galactosylation in CHO cells.

The ability to maintain antibody glycosylation profiles via polyamine modulation has numerous implications. Controlled glycosylation is crucial for optimizing therapeutic proteins, such as antibodies, ensuring the stable production of antibodies in a uniform manner of biological activities, and potentially decreasing the manufacturing cost. Supplementation of polyamine could be accomplished by the addition only of SPD to serum-free medium, offer an easy and costless method to maintain the glycan structure of mAbs produced by CHO cells cultured in the serum-free medium. This insight might influence cell line development and bioproduction, facilitating the creation of biosimilars.

“Introducing polyamines, particularly SPD, to serum-free culture medium for CHO cells may contribute to consistent manufacturing and quality control of antibody production. We hope that this research will contribute to the stable production of antibody drugs and lead to lower drug prices” concludes Dr. Higashi.

Data Assimilation (DA) is an important mathematical method for predicting turbulent flows for weather forecasting. However, the origins of the critical length scale, a crucial parameter in this method, and its dependence on the Reynolds number are not well understood. Now, researchers have developed a novel theoretical framework that treats DA as a stability problem to explain this parameter. This framework can contribute significantly to turbulence research and inspire novel data-driven methods to predict turbulence.

Weather forecasting is important for various sectors, including agriculture, military operations, and aviation, as well as for predicting natural disasters like tornados and cyclones. It relies on predicting the movement of air in the atmosphere, which is characterized by turbulent flows resulting in chaotic eddies of air. However, accurately predicting this turbulence has remained significantly challenging owing to the lack of data on small-scale turbulent flows, which leads to the introduction of small initial errors. These errors can, in turn, lead to drastic changes in the flow states later, a phenomenon known as the chaotic butterfly effect.

To address the challenge of limited data on small-scale turbulent flows, a data-driven method known as Data Assimilation (DA) has been employed for forecasting. By integrating various sources of information, this approach enables the inference of details about small-scale turbulent eddies from their larger counterparts. Notably, within the framework of DA methods, a crucial parameter known as the critical length scale has been identified. This critical length scale represents the point below which all relevant information about small-scale eddies can be extrapolated from the larger ones. Reynold’s number, an indicator of the turbulence level in fluid flow, plays a pivotal role in this context, with higher values suggesting increased turbulence. However, despite the consensus generated by numerous studies regarding a common value for the critical scale, an explanation of its origin and its relationship with Reynold’s number remains elusive.

To address this issue, a team of researchers, led by Associate Professor Masanobu Inubushi from the Tokyo University of Science, Japan, has recently proposed a theoretical framework. They treated the process of DA as a stability problem. “By considering this turbulence phenomenon as ‘synchronization of a small vortex by a large vortex’ and by mathematically attributing it to the ‘stability problem of synchronized manifolds,’ we have succeeded in explaining this critical scale theoretically for the first time,” explains Dr. Inubushi. The letter, published in Physical Review Letters on December 18, 2023, is co-authored by Professor Yoshitaka Saiki from Hitotsubashi University, Associate Professor Miki U. Kobayashi from Rissho University, and Professor Susumo Goto from Osaka University.

To this end, the research team employed a cross-disciplinary approach by combining chaos theory and synchronization theory. They focused on an invariant manifold, termed as the DA manifold, and conducted a stability analysis. Their findings revealed that the critical length scale is a key condition for DA; and is characterized by transverse Lyapunov exponents (TLEs), which ultimately dictate the success or failure of the DA process. Additionally, based on a recent discovery showing Reynolds number dependence of maximal Lyapunov exponent (LE) and the relation of TLEs with maximal LE, they concluded that the critical length scale increases with the Reynolds number, clarifying the Reynolds number dependence of the critical length scale.

Emphasizing the importance of these findings, Dr. Inubushi says, “This new theoretical framework has the potential to significantly advance turbulence research in critical problems such as unpredictability, energy cascade, and singularity, addressing a field that physicist Richard P. Feynman once described as ‘one of the remaining difficulties in classical physics.’”

In summary, the proposed theoretical framework not only enhances our understanding of turbulence, but also paves the way for novel data-driven methods that can enhance the accuracy and reliability of weather forecasting.

Let us hope for more accurate weather predictions soon!

Falls are a serious risk for older individuals and people with compromised balance. However, there are no convenient devices to train one’s reactive posture control against unexpected perturbations outside of clinical settings. To tackle this issue, researchers from Japan have developed a lightweight wearable device to perform balance exercises at home. The experimental results showcase the potential of this device to improve postural control, thus helping prevent falls and fall-related injuries.

Maintaining balance and posture is quite a complex skill, even though it comes naturally to most people. However, postural control tends to worsen with age due to various reasons, such as muscle weakness coupled with changes in vision and sensory input. This explains why older people are much more prone to falling and suffering fall-related injuries than younger individuals. Approximately 40% of older individuals have been reported to fall at least once a year.

In this regard, over the past few decades, scientists have found that postural control can be improved through various exercises, which in turn helps prevent falls. It is possible to train and cultivate the ability to perform compensatory postural adjustments (CPAs) to counteract the effects of unexpected external perturbations. Although scientists have come up with specialized devices to perform balance exercises involving unexpected perturbations, these machines are generally bulky, expensive, and complex to use, rendering them suitable for clinical settings only.

But could there be a more practical way to perform these exercises comfortably at home? In a recent study published in IEEE Journal of Translational Engineering in Health and Medicine on 31 August 2023, a research team led by Assistant Professor Masataka Yamamoto from Tokyo University of Science (TUS), Japan, and including Professor Hiroshi Takemura, Mr. Daiki Yoshikawa, and Mr. Taku Washida from TUS, as well as Professor Koji Shimatani from the Prefectural University of Hiroshima, explore this question. For their research, the researchers developed an innovative wearable balance exercise device (WBED) and investigated its effects on CPAs and reactive postural control.

The proposed wearable device uses two pneumatic artificial muscles (PAMs) to generate unexpected perturbations. These PAMs, which resemble a pair of hollow shoulder straps or suspenders, can be forced to extend or contract by regulating the air pressure inside them. For this purpose, the WBED includes a set of electronically controlled valves connected to a can of compressed gas. This enables a computer program or smartphone application to control the valves and quickly fill or empty either PAM with gas, producing a force that pulls the user sideways in a specific direction.

To test whether WBED can truly improve reactive postural control, the researchers recruited 18 healthy adult males and divided them randomly into two groups: WBED and sham. All participants first underwent an evaluation of reactive balance. They had to hold a tandem stance for one minute while air cylinders on both sides of the hips pushed them laterally at unpredictable moments. The participants in the WBED group then performed a few rounds of balance training using the proposed device, while the sham group underwent the same exercises without unexpected perturbation. Lastly, a second evaluation was performed to check for improvements in postural control.

The researchers measured several variables as outcomes during the evaluations, including peak displacement, time at peak displacement, peak velocity, and root mean square of the soles’ center of pressure. Notably, participants in the WBED group exhibited lower displacement and peak velocity after exercising with the device. “Our results prove that perturbation-based balance exercises using WBED immediately improve the subjects’ reactive postural control,” remarks Dr. Yamamoto, satisfied with their findings. “Wearable exercise devices, such as the proposed WBED, could contribute to the prevention of falls and fall-related injuries.”

In the near future, the proposed device could revolutionize how people with a high tendency to fall perform balance training, especially in countries with a steadily aging population like Japan. “We designed WBED to be lightweight, portable, and easy to use both at home and in clinical settings. It weighs only 0.9 kg and takes less than three minutes to put on,” highlights Dr. Yamamoto. By training regularly with WBED, older individuals and people undergoing physical therapy can efficiently improve postural control and responsiveness, which in turn would prevent falls and improve their overall health. Notably, WBED could also be useful for athletes who want to improve their balance.

Let us hope that wearable devices become a mainstay in balance training and health care monitoring, providing a boost to the Internet of Things technology!