Showing papers by "Tokyo University of Science published in 2023"

Data from Clonal Spreading of Tumor-Infiltrating T Cells Underlies the Robust Antitumor Immune Responses

Abstract: <div>Abstract<p>The repertoire of tumor-infiltrating T cells is an emerging method for characterizing effective antitumor T-cell responses. Oligoclonal expansion of the tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrate here that the polyclonal fraction of the tumor-reactive T-cell repertoire, consisting of relatively minor clones, increased in tumor-bearing mice treated with monoclonal anti–programmed death-ligand 1 (PD-L1) or anti-CD4, which correlated with antitumor effects. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7⁺ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones (“clonal spreading”) represents characteristics of antitumor T-cell responses induced by anti-CD4 and anti–PD-L1 treatment.</p></div>

Chiral superconductivity in UTe2 probed by anisotropic low-energy excitations

Abstract: Chiral spin-triplet superconductivity is a topologically nontrivial pairing state with broken time-reversal symmetry, which can host Majorana quasiparticles. The recently discovered heavy-fermion superconductor UTe$_2$ exhibits peculiar properties of spin-triplet pairing, and the possible chiral state has been actively discussed. However, the symmetry and nodal structure of its order parameter in the bulk, which determine the Majorana surface states, remains controversial. Here we focus on the number and positions of superconducting gap nodes in the ground state of UTe$_2$. Our magnetic penetration depth measurements for three field orientations in the Meissner state reveal the power-law temperature dependence with exponents nearly equal to 2 or less than 2, which excludes single-component spin-triplet states. The anisotropy of low-energy quasiparticle excitations indicates multiple point nodes near the $k_y$- and $k_z$-axes, evidencing that the order parameter has multiple components in a chiral complex form. We find that most consistent is a chiral $B_{3u}+iA_u$ non-unitary state, which provides fundamentals of the topological properties in UTe$_2$.

The gut lactic acid bacteria metabolite, 10-oxo-cis-6,trans-11-octadecadienoic acid, suppresses inflammatory bowel disease in mice by modulating the NRF2 pathway and GPCR-signaling

Abstract: Abstract Various gut bacteria, including Lactobacillus plantarum , possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo- cis -6, trans -11-octadecadienoic acid (γKetoC), a γ-linolenic acid-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and the LPS-induced production of inflammatory cytokines. The treatment with γKetoC markedly increased the protein level of NRF2, a master transcription factor for antioxidant responses, and the mRNA level of Hmox1 , a target gene of NRF2, in bone marrow-derived dendritic cells (BMDCs). Although γKetoC significantly suppressed the LPS-induced activation of control BMDCs, particularly the secretion of IL-12/23p40, the suppressive effects of γKetoC were reduced in Nrf2 -/- BMDCs. GW9508, an agonist of GPR40/GPR120, inhibited the release of cytokines from LPS-stimulated BMDCs without activating the NRF2 pathway. We evaluated the role of NRF2 in the anti-inflammatory effects of γKetoC in a dextran sodium sulfate-induced colitis model. The oral administration of γKetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6J and Nrf2 +/- (C57BL/6N) mice with colitis. In contrast, the pathology of colitis was deteriorated in Nrf2 -/- mice even with the administration of γKetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway in γKetoC-mediated anti-inflammatory responses.

Cover Feature: Polarity and Dielectric Property Control Triggered by a Coordinated Solvent Molecule Exchange in Luminescent Mononuclear Aluminium(III) Complexes (Chem. Eur. J. 33/2023)

Abstract: Luminescent mononuclear aluminium(III) complexes that can control molecular arrangements and dielectric properties by exposure to solvent vapor in the solid state have been reported. In this image, the left side represents the nonpolar structure under MeOH vapor, and the right side represents the polar structure under DMSO vapor. The second harmonic generation (SHG) behavior attributed to the structural transformation to the polar structure is depicted as red and green lights. More information can be found in the Research Article by F. Kobayashi, M. Tadokoro, and co-workers (DOI: 10.1002/chem.202203937).

Mechanism of Chiral-Selective Aminoacylation of an RNA Minihelix Explored by QM/MM Free-Energy Simulations

Abstract: Aminoacylation of a primordial RNA minihelix composed of D-ribose shows L-amino acid preference over D-amino acid without any ribozymes or enzymes. This preference in the amino acylation reaction likely plays an important role in the establishment of homochirality in L-amino acid in modern proteins. However, molecular mechanisms of the chiral selective reaction remain unsolved mainly because of difficulty in direct observation of the reaction at the molecular scale by experiments. For seeking a possible mechanism of the chiral selectivity, quantum mechanics/molecular mechanics (QM/MM) umbrella sampling molecular dynamics (MD) simulations of the aminoacylation reactions in a modeled RNA were performed to investigate differences in their free-energy profiles along the reactions for L- and D-alanine and its physicochemical origin. The reaction is initiated by approaching a 3′-oxygen of the RNA minihelix to the carbonyl carbon of an aminoacyl phosphate oligonucleotide. The QM/MM umbrella sampling MD calculations showed that the height of the free-energy barrier for L-alanine aminoacylation reaction was 17 kcal/mol, which was 9 kcal/mol lower than that for the D-alanine system. At the transition state, the distance between the negatively charged 3′-oxygen and the positively charged amino group of L-alanine was shorter than that of D-alanine, which was caused by the chirality difference of the amino acid. These results indicate that the transition state for L-alanine is more electrostatically stabilized than that for D-alanine, which would be a plausible mechanism previously unexplained for chiral selectivity in the RNA minihelix aminoacylation.

Japan Coast Guard's GNSS-A seafloor geodetic observation: analysis scheme and development of data format

Abstract: The GNSS-Acoustic ranging combination technique (GNSS-A) is a method to precisely measure the absolute position of the seafloor benchmark in the centimeter level by combining GNSS and acoustic ranging. The Hydrographic and Oceanographic Department of the Japan Coast Guard (JCG) has been conducting GNSS-A observation at 27 seafloor sites along the Japan Trench and the Nankai Trough named the Seafloor Geodetic Observation Array (SGO-A), to reveal the geophysical processes related to megathrusts that occur at the subduction zones along the Japanese archipelago. From the observations at the SGO-A sites along the Japan Trench, we have discovered the co- and postseismic processes of the 2011 Tohoku-oki Earthquake (Sato et al. 2011; Watanabe et al. 2021). Heterogeneous interplate coupling (Yokota et al. 2016) and shallow slow slip events (Yokota and Ishikawa 2020) have been revealed by observation along the Nankai Trough.Currently, JCG conducts routine analysis using the open-source GNSS-A analysis software GARPOS (Watanabe et al. 2020). We are aiming an &#8220;open&#8221; GNSS-A, and the SGO-A coordinate time series obtained from the routine analysis are published online. In this presentation, we review our observation and analysis methods, and discuss on the latest observation results obtained at the SGO-A sites. Additionally, we also introduce our GNSS-A data format, which we have been discussing in the seafloor geodesy data standardization task force of the Inter-Commission Committee on Marine Geodesy (ICCM) in the International Association of Geodesy.

First Demonstration of 512-Color Shift Keying Signal Demodulation Using Neural Equalization for Optical Camera Communication

Abstract: This paper experimentally demonstrates 512 color shift keying (CSK) signal transmission for optical camera communication (OCC). We achieved error-free operation with a CMOS image sensor module and a multi-label classification neural network-based equalizer.

Data from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

Abstract: <div><p>Resistance to immune checkpoint blockade remains challenging in patients with non–small cell lung cancer (NSCLC). Tumor-infiltrating leukocyte (TIL) quantity, composition, and activation status profoundly influence responsiveness to cancer immunotherapy. This study examined the immune landscape in the NSCLC tumor microenvironment by analyzing TIL profiles of 281 fresh resected NSCLC tissues. Unsupervised clustering based on numbers and percentages of 30 TIL types classified adenocarcinoma (LUAD) and squamous cell carcinoma (LUSQ) into the cold, myeloid cell–dominant, and CD8⁺ T cell–dominant subtypes. These were significantly correlated with patient prognosis; the myeloid cell subtype had worse outcomes than the others. Integrated genomic and transcriptomic analyses, including RNA sequencing, whole-exome sequencing, T-cell receptor repertoire, and metabolomics of tumor tissue, revealed that immune reaction–related signaling pathways were inactivated, while the glycolysis and K-ras signaling pathways activated in LUAD and LUSQ myeloid cell subtypes. Cases with <i>ALK</i> and <i>ROS1</i> fusion genes were enriched in the LUAD myeloid subtype, and the frequency of <i>TERT</i> copy-number variations was higher in LUSQ myeloid subtype than in the others. These classifications of NSCLC based on TIL status may be useful for developing personalized immune therapies for NSCLC.</p>Significance:<p>The precise TIL profiling classified NSCLC into novel three immune subtypes that correlates with patient outcome, identifying subtype-specific molecular pathways and genomic alterations that should play important roles in constructing subtype-specific immune tumor microenvironments. These classifications of NSCLC based on TIL status are useful for developing personalized immune therapies for NSCLC.</p></div>

Nature-Inspired and Evolutionary Techniques for Automation

Abstract: In this chapter, nature-inspired and evolutionary techniques (ET) will be introduced for treating automation problems in advanced planning and scheduling, assembly line system, logistics, and transportation. ET is the most popular meta-heuristic method for solving NP-hard optimization problems. In the past few years, ETs have been exploited to solve design automation problems. Concurrently, the field of ET reveals a significant interest in evolvable hardware and problems such as scheduling, placement, or test pattern generation. The rest of this chapter is organized as follows. First, the background and developments of nature-inspired and ETs are described. Then basic schemes and working mechanism of genetic algorithms (GA), swarm intelligence, and other nature-inspired optimization algorithms are given. Multi-objective evolutionary algorithms for treating optimization problems with multiple and conflicting objectives are presented. Features of evolutionary search, such as hybrid evolutionary search, enhanced EA via learning, and evolutionary design automation are presented. Next, the various applications based on ETs for solving nonlinear/combinatorial optimization problems in automation are surveyed. In terms of advanced planning and scheduling (APS), the facility layout problems, planning and scheduling of manufacturing systems, and resource-constrained project scheduling problems are included. In terms of assembly line system, various assembly lines balancing (ALB) models are included. In terms of logistics and transportation, location allocation models and various types of logistics network models are included.

Data from Clonal Spreading of Tumor-Infiltrating T Cells Underlies the Robust Antitumor Immune Responses

Abstract: <div>Abstract<p>The repertoire of tumor-infiltrating T cells is an emerging method for characterizing effective antitumor T-cell responses. Oligoclonal expansion of the tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrate here that the polyclonal fraction of the tumor-reactive T-cell repertoire, consisting of relatively minor clones, increased in tumor-bearing mice treated with monoclonal anti–programmed death-ligand 1 (PD-L1) or anti-CD4, which correlated with antitumor effects. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7⁺ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones (“clonal spreading”) represents characteristics of antitumor T-cell responses induced by anti-CD4 and anti–PD-L1 treatment.</p></div>

Fluorinated [2]rotaxanes with spirofluorene motifs: a non-symmetric distribution of the ring component along the axle component

Abstract: The distribution of the ring component in [2]rotaxanes was modulated by the introduction of a less symmetric spiro ring.

Butyrate, valerate, and niacin ameliorate anaphylaxis by suppressing IgE-dependent mast cell activation: Roles of GPR109A, PGE₂, and epigenetic regulation

Abstract: Abstract Short chain fatty acids (SCFAs) were recently shown to modulate the development and functions of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) are not fully understood. We found that the oral administration of valerate or butyrate ameliorated passive systemic anaphylaxis in mice. Butyrate and valerate suppressed the IgE-mediated degranulation of bone marrow-derived MCs, which were eliminated by pertussis toxin and by the knockdown of Gpr109a . A treatment with trichostatin A suppressed IgE-mediated MC activation and reduced the surface expression level of FcεRI on MCs. Acetylsalicylic acid and indomethacin attenuated the suppressive effects of SCFAs on degranulation. The degranulation degree was significantly decreased by the treatment with PGE 2 whose release from MCs was markedly enhanced by SCFAs. The SCFA-mediated amelioration of anaphylaxis was exacerbated by COX inhibitors and an EP3 antagonist. The administration of niacin, a ligand of GPR109A, alleviated the symptoms of passive cutaneous anaphylaxis, which was inhibited by COX inhibitors and the EP3 antagonist. Key Messages Short chain fatty acids (SCFAs), particularly butyrate and valerate, suppress the IgE-mediated activation of mast cells (MCs) in vivo and in vitro . SCFAs enhance the release of PGE 2 from MCs, which inhibits the IgE-mediated activation of MCs. Niacin, a ligand of GPR109A, ameliorates IgE-dependent anaphylaxis. The administration of COX inhibitors or an antagonist of PGE 2 receptor 3 (EP3) inhibited the suppressive effects of butyrate and niacin on IgE-dependent anaphylaxis.

Phospholipid signaling, lipase

Abstract: Phospholipids are the major components of the plasma membrane. They are metabolized by phospholipases, which constitute a class of hydrolases that catalyze the hydrolysis of acyl esters and phosphate esters on phospholipids. Phospholipases are classified according to their action on the phospholipid substrate molecule. Phospholipase A 2 triggers the production of lipid mediators and remodels the membrane phospholipids. Phospholipase C hydrolyzes the plasma membrane phosphatidylinositol 4,5-bisphosphates and generates diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C and elevation of cytosolic Ca 2+ levels. Phospholipase D generates phosphatidic acid, which leads to the negative curvature of the plasma membrane. This chapter mainly focuses on the phospholipase-mediated phospholipid metabolism process in the plasma membranes of mammalian cells.

Partial regularity of minimizers for double phase functionals with variable exponents

Abstract: Abstract The aim of this article is to study partial regularity of a minimizer u: Ω ⊂ R n → R N for a double phase functional with variable exponents: ∫ (|| Du || A p(x) + a(x) ||Du|| A q(x) ) dx , where || . || stands for the norm deduced from a positive definite sufficiently continuoustensor field A:=(A ij αβ (x,u)) ( (x,u) ∈ Ω × R N ). We show that a minimizer u is in the class C 1,γ (Ω 1 ;R N ) for some constant γ ∈ (0,1) and open subset Ω 1 ⊂ Ω . We obtain also an estimate for the Hausdorff dimension of Ω \ Ω 1 . MSC Classification: 35J20 , 35J47 , 35J60 , 49N60

Solving max-plus linear systems by level sparsification

Abstract: In this study, an algorithm for solving max-plus linear systems is discussed. Such a system is applied to many problems, such as control and scheduling, and is equivalent to the mean-payoff game. To reduce the computational time required to solve max-plus linear systems, we improve the alternating method, which is a well-known algorithm for the problem. In max-plus arithmetics, small numbers rarely contribute to the results. Based on this observation, our method, called level sparsification, selects some large entries of matrices as active ones and ignore other entries by replacing with a fixed value. Depending on the number of selected entries, we propose two types of sparsification and experiment with the performance compared to the original alternating method.

Immunostimulatory effects of<i>Bacillus coagulans</i>SANK70258

Abstract: Abstract Specific intestinal bacteria modulate immunoresponses through various pathways, and several probiotic bacteria have been identified as immunostimulants by screening. In the present study, we evaluated the immunomodulating effects of Bacillus coagulans SANK70258 ( B. coagulans SANK70258), a spore-forming and lactic acid-producing bacterium usable as food supplement for human and animals. We found that treatment of mouse splenocytes with γ-ray irradiated B. coagulans SANK70258 induced high amount of IFN-γ in comparison with 7 kinds of typical lactic acid bacteria. Further analyses using splenocytes revealed that NK cell is a major source of IFN-γ, and B . coagulans SANK70258-induced IFN-γ production was inhibited by neutralization of IL-12 or IL-23, depletion of CD11c + cells, and inhibition of NFκB. B. coagulans SANK70258 also induced release of IFN-γ from activated CD8 + T cells, and increased expression of chemokine receptors in CD8 + T cells. B. coagulans SANK70258-treatment induced production of cytokines from bone marrow-derived dendritic cells, which is reduced by knockdown of Tlr2 and Nod2. B. coagulans SANK70258-treatment also induced IgA production from Peyer’s patch cells with high level among tested lactic bacteria. The oral intake of γ-ray irradiated B. coagulans SANK70258 significantly increased intestinal IgA levels and IgA-expressing B cells in the Peyer’s patch of mice. Taken together, we conclude that B. coagulans SANK70258 possesses high activity as immunostimulant inducing production of IFN-γ and IgA.

Time-to-build and capacity expansion

Abstract: Abstract In this study, we investigate a firm’s optimal investment timing and capacity decisions in the presence of uncertain time-to-build. The firm raises revenue from the investment after an uncertain amount of time elapses, while the time-to-build of the follow-up investment is expectedly shorter than that of the initial investment due to learning by doing. We derive the optimal investment strategies and examine the impact of time-to-build on the investment dynamics. We show that both the initial and follow-up investment can be made earlier in the presence of time-to-build than they would in the absence of the lags, especially in a volatile market. This is in contrast to the case of a single investment, whose timing is always delayed by the time-to-build. Furthermore, the capacity of the follow-up project dominates that of the initial project in the presence of time-to-build, whereas the latter dominates the former in the absence of lags. The capacity choice of each project, however, is nonmonotone with respect to the size of the lags. We also show that uncertainty delays investment even when the investment involves lags but the negative impact softens in the presence of time-to-build and learning effects.

Concept of Sustainable Supply Chain Management Using Multi-agent System: Negotiation by Linear Physical Programming

Abstract: Abstract Industry and academia are both making efforts to realize a sustainable society; an important part of these efforts is to ensure the sustainability of the supply chains that support our daily life. Sustainable supply chains are more complex than traditional supply chains, and they involve a combination of multiple issues. Multiple plans must be used to deal with these issues. However, these plans often conflict with each other. To manage a sustainable supply chain, an integrated approach is needed to operate multiple plans for multiple issues. This paper introduces a research concept for integrated sustainable supply chain management using a multi-agent system. An agent executing a plan for an issue autonomously negotiates with other agents and avoids conflicts. Linear physical programming used for negotiation balances agents’ utility and ensures that all plans function well. Through this research, we provide an example of the simultaneous operation of multiple plans in a sustainable supply chain, aiming at the social implementation of sustainable supply chains.

Applying AIDAF for Digital Transformation Toward Ecosystem in Global Enterprise

Abstract: Enterprises and societies currently face essential challenges, and digital transformation can contribute to their resolution. Enterprise architecture (EA) is useful for promoting digital transformation in global companies and information societies covering ecosystem partners. The advancement of new business models can be promoted with digital platforms and architectures for Industry 4.0 and Society 5.0. Therefore, products from the sector of healthcare, manufacturing and energy, etc. can increase in value. The adaptive integrated digital architecture framework (AIDAF) for Industry 4.0 and the design thinking approach is expected to promote and implement the digital platforms and digital products for healthcare, manufacturing and energy communities more efficiently. In this paper, we propose various cases of digital transformation where digital platforms and products are designed and evaluated for digital IT, digital manufacturing and digital healthcare with Industry 4.0 and Society 5.0. The vision of AIDAF applications to perform digital transformation in global companies is explained and referenced, extended toward the digitalized ecosystems such as Society 5.0 and Industry 4.0.