Open Regions Research Articles

La Alianza del Pacífico: más cooperación que integración

The Pacific Alliance was established as a strategy of open regionalism in the region that seeks closer ties with Asia-Pacific and greater interdependence among its members. However, 13 years after the signing of the agreement, the results are more cooperation than integration. The changing Latin American political landscape shows a weakening of this multilateral organization, giving way to regionalism and a soft and pendular leadership. This article mentions its stages, achievements and future possibilities. Its evolution and trajectory have not been homogeneous, but rather present ups and downs and the possibility of new issues. The methodology is qualitative, combining primary and secondary sources, and counterbalances media with academic analysis.

Structural and dynamical properties of two dimensional disordered metal chalcogenides AB (A [formula omitted] Zn, Cd; B [formula omitted] S, Se): A classical molecular dynamic study

In recent years, the synthesis of two-dimensional (2D) materials, particularly the crystalline and disordered phases of 2D transition metal chalcogenides (TMCs), has gained considerable attention due to their wider electronic band gaps. This distinctive feature is pivotal in shaping their potential applications in solar cells, sensors, field-effect transistors (FETs), and photocatalysis for water decomposition. In the present study, we report molecular dynamics simulation of 2d disordered configuration of ZnX and CdX (X: S, Se) compounds using the Stillinger–Weber potential. We have explored their structural features by calculating their radial distribution functions and ring statistics. These systems are thermodynamically stable. The disordered network with numerous voids in these compounds play a pivotal role in lowering their melting temperature compared to their 2D crystalline counterparts, which falls within the range of 600 K to 700 K. The phonon density of states for all these systems shows a higher number of lower frequency (acoustic) modes than optical modes, which is understandably due to the presence of open regions and 2-fold sites in such systems.

ROLE OF ASEAN IN ECONOMIC INTEGRATION PROCESSES IN ASIA

ASEAN plays significant role in the economic integration processes in Asia. The financial crisis in 1997 fostered the integration processes between Asian countries. Asian integration mainly characterized by the open regionalism which promotes economic integration and trade liberalization between states. Asian regionalism is market-driven and open to economic cooperation, trade and investment. ASEAN promote the internal integration between member states of the organization and external integration between ASEAN and partners. ASEAN’s initiativesthat focused on external integration such as ASEAN Regional Forum, APEC, East Asia Summit, ASEAN+3 and others. Through its collaborative efforts and commitment to fostering economic partnerships, the Asian region has witnessed substantial progress in trade, investme nt and economic cooperation. The article analyzes the intra-regional trade, investment flows , economic cooperation initiatives between ASEAN and East Asian countries. This article examine s economic relations of ASEAN with China, Japan and South Korea in the framework of ASEAN+3. The ASEAN+3 forum fosters economic cooperation between Southeast Asia and East Asian countries such as China, Japan, South Korea. The cooperation between ASEAN and China, Japan, South Korea mainly focused on the economic cooperation, mainly trade, FDI Investment and digital economy.ASEAN+3 considered asan important platform for promoting regiona l cooperation between the countries of Southeast Asia and East Asia.

The chromatin landscape of high-grade serous ovarian cancer metastasis identifies regulatory drivers in post-chemotherapy residual tumour cells

Disease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.

Analysis of chromatin accessibility in peripheral blood mononuclear cells from patients with early-stage breast cancer.

Objective: This study was aimed at exploring a specific open region of chromatin in the peripheral blood mononuclear cells (PBMCs) of patients with breast cancer and evaluating its feasibility as a biomarker for diagnosing and predicting breast cancer prognosis. Methods: We obtained PBMCs from breast cancer patients and healthy people for the assay for transposase-accessible chromatin (ATAC) sequencing (n = 3) and obtained the GSE27562 chip sequencing data for secondary analyses. Through bioinformatics analysis, we mined the pattern changes for chromatin accessibility in the PBMCs of breast cancer patients. Results: A total of 1,906 differentially accessible regions (DARs) and 1,632 differentially expressed genes (DEGs) were identified via ATAC sequencing. The upregulated DEGs in the disease group were mainly distributed in the cells, organelles, and cell-intima-related structures and were mainly responsible for biological functions such as cell nitrogen complex metabolism, macromolecular metabolism, and cell communication, in addition to functions such as nucleic acid binding, enzyme binding, hydrolase reaction, and transferase activity. Combined with microarray data analysis, the following set of nine DEGs showed intersection between the ATAC and microarray data: JUN, MSL2, CDC42, TRIB1, SERTAD3, RAB14, RHOB, RAB40B, and PRKDC. HOMER predicted and identified five transcription factors that could potentially bind to these peak sites, namely NFY, Sp 2, GFY, NRF, and ELK 1. Conclusion: Chromatin accessibility analysis of the PBMCs from patients with early-stage breast cancer underscores its potential as a significant avenue for biomarker discovery in breast cancer diagnostics and treatment. By screening the transcription factors and DEGs related to breast cancer, this study provides a comprehensive theoretical foundation that is expected to guide future clinical applications and therapeutic developments.

Abstract B011: FOXA1 as a pioneer factor in ERα-DNA interactions and its therapeutic potential in ER+ breast cancer: Insights from ChIP-seq and GWAS in Hispanic populations

Abstract Forkhead box A1 (FOXA1) acts as a pioneer factor for Estrogen Receptor alpha (ERα), playing a crucial role in determining where ERα binds to DNA and regulates gene expression in breast cancer cells. A pioneer factor is a class of transcription factors (TF) that is responsible for opening the chromatin to allow other TFs to attach and activate transcription of that gene. FOXA1 acts as a facilitator for ERα-DNA interactions. It binds to specific DNA regions, opening the chromatin for ERα to bind. It “pre-marks” these sites in the genome even in the absence of estrogen. In fact, FOXA1 is frequently overexpressed in ER+ breast cancers, suggesting it has a crucial role in driving tumor growth. As such, FOXA1 is an attractive therapeutic target that already serves as a great biomarker for many types of breast cancers. Inhibiting FOXA1 can potentially block ER activity and inhibit growth of ER+ breast cancer, especially in those resistant to anti-estrogen therapies, such as tamoxifen. In this project, we identified sites that FOXA1 opens and correlated them with SNP mutations commonly found in the Hispanic population. The presence of these SNPs portends a worse outcome in Hispanic patients. To assess which open chromatin regions are crucial for breast cancer pathogenesis, a ChIP-seq analysis was done on vehicle-treated and estrogen-treated samples to determine FOXA1 binding sites. After identifying gained, lost, and differentially expressed peaks set, these were compared to genome-wide association studies (GWAS) of Hispanic patients to develop an understanding of how much overlap is common between sites of mutations and open sections of chromatin due to FOXA1. Through our analysis, we uncovered a subset of FOXA1 binding sites that overlap with sites of inherited mutation in Hispanic patients. This informs on the subset of genes that are linked to breast cancer and potential therapeutic targets. Citation Format: Hemakshat Sharma, Alyssa Maria Arreola, Frances L. Heredia, Hector L. Franco, Julie Dutil. FOXA1 as a pioneer factor in ERα-DNA interactions and its therapeutic potential in ER+ breast cancer: Insights from ChIP-seq and GWAS in Hispanic populations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B011.

Epigenomic, transcriptomic and proteomic characterizations of reference samples.

A variety of newly developed next-generation sequencing technologies are making their way rapidly into the research and clinical applications, for which accuracy and cross-lab reproducibility are critical, and reference standards are much needed. Our previous multicenter studies under the SEQC-2 umbrella using a breast cancer cell line with paired B-cell line have produced a large amount of different genomic data including whole genome sequencing (Illumina, PacBio, Nanopore), HiC, and scRNA-seq with detailed analyses on somatic mutations, single-nucleotide variations (SNVs), and structural variations (SVs). However, there is still a lack of well-characterized reference materials which include epigenomic and proteomic data. Here we further performed ATAC-seq, Methyl-seq, RNA-seq, and proteomic analyses and provided a comprehensive catalog of the epigenomic landscape, which overlapped with the transcriptomes and proteomes for the two cell lines. We identified >7,700 peptide isoforms, where the majority (95%) of the genes had a single peptide isoform. Protein expression of the transcripts overlapping CGIs were much higher than the protein expression of the non-CGI transcripts in both cell lines. We further demonstrated the evidence that certain SNVs were incorporated into mutated peptides. We observed that open chromatin regions had low methylation which were largely regulated by CG density, where CG-rich regions had more accessible chromatin, low methylation, and higher gene and protein expression. The CG-poor regions had higher repressive epigenetic regulations (higher DNA methylation) and less open chromatin, resulting in a cell line specific methylation and gene expression patterns. Our studies provide well-defined reference materials consisting of two cell lines with genomic, epigenomic, transcriptomic, scRNA-seq and proteomic characterizations which can serve as standards for validating and benchmarking not only on various omics assays, but also on bioinformatics methods. It will be a valuable resource for both research and clinical communities.

Abstract C078: Chromatin accessibility profiling of human pancreatic tumors reveals epigenetic features of malignant and stromal cell subtypes

Abstract Pancreatic ductal adenocarcinoma (PDAC) disease progression involves complex cell state transitions in both malignant and non-malignant populations within the tumor microenvironment. To uncover PDAC cell states and epigenetic features associated with clinical outcome, we profiled 40 tumor samples (33 primary tumors and 7 metastases) from 39 patients with single cell ATAC-seq, along with 10 sample-matched single cell RNA-seq profiles. Through topic modeling of high dimensional chromatin data, we uncovered distinct cis-regulatory networks underlying the classical and basal-like molecular subtypes of PDAC, which showed differential activity in basal-classical hybrid cells. Furthermore, delineation of epigenetic alterations by basal, classical, and hybrid subtypes revealed a core set of chromatin regions opened in all PDAC subtypes relative to ductal and acinar cells. These universally open regions showed striking overlap with gastrointestinal enhancers, highlighting a common endoderm lineage infidelity process across pancreatic tumors. Within the stromal compartment, we identified novel regulators of myofibroblastic cancer-associated fibroblasts (myCAFs) and inflammatory CAFs (iCAFs) from enhancer networks active in each CAF subtype. Importantly, our data uncover a highly prognostic gene program active in only one of two distinct myCAF chromatin states found in our data, highlighting a putative tumor-promoting myCAF subpopulation. Our work provides a high-resolution description of epigenetic cell state heterogeneity in PDAC, revealing novel regulators and gene programs associated with PDAC subtypes and clinical outcome. Citation Format: Kevin MacPherson-Hawthorne, Jason M. Link, Patrick Worth, Brett Sheppard, Andrew Fields, Colin Daniel, Andrew Nishida, Carl Pelz, Trent Waugh, Ethan Agritelle, John Muschler, Andrew Adey, Rosalie Sears. Chromatin accessibility profiling of human pancreatic tumors reveals epigenetic features of malignant and stromal cell subtypes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C078.

Symbolic dynamics for pointwise hyperbolic systems on open regions

Abstract Under certain conditions, we construct a countable Markov partition for pointwise hyperbolic diffeomorphism $f:M\rightarrow M$ on an open invariant subset $O\subset M$ , which allows the Lyapunov exponents to be zero. From this partition, we define a symbolic extension that is finite-to-one and onto a subset of O that carries the same finite f-invariant measures as O. Our method relies upon shadowing theory of a recurrent-pointwise-pseudo-orbit that we introduce. As a canonical application, we estimate the number of closed orbits for f.

Abstract 08: Genome-wide Maps of Human Kidney Proximal Tubules and Thick Ascending Limbs of Henle reveal an Enrichment for Human Blood Pressure associated Polymorphisms

GWAS has identified >1,000 blood pressure (BP)-associated sentinel SNPs, most of which (>90%) are intronic and intergenic. How they regulate BP-relevant genes remains an open question. We hypothesized many SNPs would reside within cis -regulatory elements specific to nephron segments critical to sodium resorption such as proximal tubule (PT) and thick ascending limb (TAL). To address this, we developed chromatin state (ATAC-seq) and transcriptome (RNA-seq) maps from manually dissected human PT and medullary TAL (mTAL) segments. We identified 216,168 and 179,467 open regions in PT and mTAL, respectively, with the majority (70%) being unique to one tissue. Interestingly, peaks shared between the two segments resided more frequently in promoters, whereas unique peaks were more often found in distal introns or intergenic regions, suggesting they lie within enhancers ( Figure 1A ). Both chromatin state and transcriptomic data demonstrated a correlation between open chromatin peaks within gene promoters and mRNA levels (r=0.11; p<4.6e-16). This correlation was weaker at open regions distal to the promoter, illustrating the difficulty of mapping distal open regions to the gene(s) they regulate. We hypothesized these open regions would be enriched for BP-relevant SNPs. We curated 1,071 bp-associated SNPs and found 87 and 67 in mTAL and PT, open regions respectively, many of which are near BP-relevant genes. This enrichment was significant based on 10 4 randomizations (pValue 10 -4 ) ( Figure 1B ). We conclude that these novel tissue-specific chromatin maps can be used to identify potential mechanisms by which SNPs influence gene expression and BP. Additional studies will be needed to demonstrate both causality and molecular mechanisms.

Abstract P215: The reninness score: integrative analysis of multi-omic data to define renin cell identity.

Renin cell (RC) descendants regain the endocrine renin phenotype to overcome homeostatic threats, a process known as recruitment. The determinants that control the identity, fate, and recruitment of RCs are not well understood. We aim to 1) define the chromatin pattern that determines RC identity; and 2) develop a computational tool to score samples by similarity to that pattern. We compared open chromatin regions (ATAC-seq) between non-renin-expressing (n = 184) and renin-expressing samples (n = 19) from three different sources and stimulation states: 1) primary RCs in basal state (WT); 2) primary RCs chronically stimulated to produce renin (Recruited); and 3) constitutively renin-expressing tumoral cells. Differential analyses between the three types of RCs and the non-RCs revealed 1,525 unique open chromatin regions shared in at least two RC groups, including regions associated with RC-specific genes: Ren1 and Akr1b7. Increased accessibility regions in RC groups are cell type specific and enriched in renin-related GO terms ( e.g., cAMP and Notch signaling pathway). The bZip family ( e.g. , Atf3, p < 10 -2147 ) was the most enriched motifs in tumoral cells, and MEF2 family ( e.g. , MEF2a, p < 10 -91 ) in primary cells. We did not find a unique set of TFs specific to the Recruited group, indicating that renin recruitment may not be regulated by a recruitment-specific factor family, but could instead be driven by post-translational modification, differential co-factors, or epigenetic modifications. Next, we used a machine-learning approach to calculate a "reninness" score by training a genomic region model with renin and non-renin bulkATAC-seq data. We identified a cluster of regions (n = 112,992) around the trained renin label, which included 89% (21,820 of 24,612) of the regions with increased accessibility from the differential analyses. We calculated the reninness score based on the distance between the trained label and the predicted bulkATA sample embeddings using the trained model. Homogeneous WT RCs had the highest score, followed by renin-expressing tumoral and primary cells. Non-RCs had the lowest scores. We also adapted bulkATAC region-embedding models to pseudo-bulk ATAC- and scATAC-seq data. The observed reninness scores show that the model can also capture differences in renin recruitment potential. In conclusion, we identified the chromatin configurations defining the identity and recruitment of RCs and developed a computational score to quantify it.

Design of metal foam baffle to enhance the thermal-hydraulic performance of shell and tube heat exchanger

Solid baffles are widely used in shell and tube heat exchanger (STHX), while the highly increased flow resistance and dead zones remain serious drawbacks in the applications. To address this issue, metal foam baffle is proposed in this study to replace solid baffle. The numerical model with considering the thermal non-equilibrium between fluid and foam baffles was established. Laminar flow is assumed in the foam baffles region and the realizable k-ε turbulence model is assumed in the open region. Effects of porosity, pore density, thickness and number of foam baffle (N) on the performance were examined. Results show the foam baffles always lead to lower pressure drop of STHX compared to the solid baffles. Compared to five 2 mm thick solid baffles, five 6 mm thick metal baffles with the porosity of 0.80, 0.85 and 0.90 results higher outlet temperature at the pore density greater than 80, 120 and 160 PPI, respectively. The metal foam baffle leads to higher outlet water temperature compared with solid baffles at the baffle number N ≤ 7. The foam baffles with optimum pore parameters reduced the pressure drop by 12.9 % and increase the outlet and inlet temperature difference by 31.0 % compared to the solid baffles.

Patent infringement litigation, executive team risk appetite and corporate innovation

ABSTRACT Comprehensively deepening the trial mechanism of patent infringement litigation is important for optimizing law environment for scientific and technological innovation. However, the growing frequency for patent infringement lawsuits significantly impacts the corporate innovation. The existing literature focuses on the direct relationship between patent infringement litigation and corporate innovation without exploring the mechanisms. Based on this, this paper analyzed the effect between patent infringement litigation and innovation and heterogeneity using a fixed effects model on the theoretical model basis. The study found that patent infringement litigation has a positive impact on innovation investment; patent infringement litigation promotes innovative activity through foreign direct investment; executive team risk appetite negatively moderates the relationship between patent infringement litigation and firms’ innovation investment. Patent infringement litigation has a more significant incentive effect on the innovation activities of state-owned enterprises, more open regions, and in the northeast and east regions. This paper not only reveals the mechanism that judicial litigation affects innovation activities but also provides a reference basis to solve patent disputes.

N-myc and STAT interactor degrades interferon regulatory factor 7 mediated type I interferon signaling to promote duck Tembusu virus replication

N-myc and STAT interactor (NMI) is an interferon-induced protein, which plays a variety of biological functions by participating in signal transduction and transcriptional activation, it has been reported to regulate antiviral response of different viruses in many species. However, the role of NMI in ducks during Duck Tembusu Virus (DTMUV) infection is completely unknown. In order to reveal whether duck NMI (duNMI) is involved in the antiviral response in the process of DTMUV infection and its role, we cloned and identified duNMI gene, and conducted sequence analysis of duNMI, the open reading frame region of duNMI gene is 1,137 bp, encoding 378 amino acid residues (aa), including 3 domains, Coiled-coil domain (22-126aa), NMI/IFP 35 domain 1 (NID1) domain (174-261aa) and NMI/IFP 35 domain 2 (NID2) domain (272-360aa). Analysis of tissue distribution of duNMI in 7-day-old ducks shows that the expression of duNMI is the highest in harderian gland, followed by small intestine and pancreas. Subsequently, we found that mRNA level of duNMI increases significantly after DTMUV stimulation, and overexpression of duNMI inhibits DTMUV replication in a dose-dependent manner. Besides, duNMI inhibits the transcriptional activity of IFN-I related cytokines. Specifically, we confirmed that duNMI interacts with duck regulatory factor 7 (duIRF7) through NID1 and NID2 domains and inhibit its expression and activated-IFN-β. These results support that duNMI is an inhibitor of antiviral innate immune response in the process of DTMUV infection, which will provide a theoretical basis for the prevention of DTMUV infection.

On the Physical Consistency of an Open Quantum Region with a Classical Reservoir in Molecular Simulation

AbstractThe possibility of treating a molecular liquid in an open region at ab initio electronic resolution embedded in a classical reservoir of energy and particles, is investigated. Because of its challenging properties and its relevance in many field of current research, the system chosen as prototype of molecular liquid is water at room conditions. A numerical protocol based on the mathematical model of open particle system is applied and the results are compared with results of a full ab initio simulation of reference. The key conclusion is that one can claim the existence of a mandatory minimal size of the quantum region in which structural and electronic properties reproduce those of reference and, at the same time, the exchange of molecules with the environment takes place as expected. This work provides a proof of concept about the possibility to systematically define a physically well founded open quantum system embedded in a classical environment. In turn, the proof of concept is a key information for the design of numerically efficient algorithms for ab initio molecular dynamics simulations of open systems.

Cell-free DNA from germline TP53 mutation carriers reflect cancer-like fragmentation patterns

Germline pathogenic TP53 variants predispose individuals to a high lifetime risk of developing multiple cancers and are the hallmark feature of Li-Fraumeni syndrome (LFS). Our group has previously shown that LFS patients harbor shorter plasma cell-free DNA fragmentation; independent of cancer status. To understand the functional underpinning of cfDNA fragmentation in LFS, we conducted a fragmentomic analysis of 199 cfDNA samples from 82 TP53 mutation carriers and 30 healthy TP53-wildtype controls. We find that LFS individuals exhibit an increased prevalence of A/T nucleotides at fragment ends, dysregulated nucleosome positioning at p53 binding sites, and loci-specific changes in chromatin accessibility at development-associated transcription factor binding sites and at cancer-associated open chromatin regions. Machine learning classification resulted in robust differentiation between TP53 mutant versus wildtype cfDNA samples (AUC-ROC = 0.710–1.000) and intra-patient longitudinal analysis of ctDNA fragmentation signal enabled early cancer detection. These results suggest that cfDNA fragmentation may be a useful diagnostic tool in LFS patients and provides an important baseline for cancer early detection.

Muscle growth differences in Lijiang pigs revealed by ATAC-seq multi-omics.

As one of the largest tissues in the animal body, skeletal muscle plays a pivotal role in the production and quality of pork. Consequently, it is of paramount importance to investigate the growth and developmental processes of skeletal muscle. Lijiang pigs, which naturally have two subtypes, fast-growing and slow-growing, provide an ideal model for such studies by eliminating breed-related influences. In this study, we selected three fast-growing and three slow-growing 6-month-old Lijiang pigs as subjects. We utilized assay for transposase-accessible chromatin with sequencing (ATAC-seq) combined with genomics, RNA sequencing, and proteomics to screen for differentially expressed genes and transcription factors linked to increased longissimus dorsi muscle volume in Lijiang pigs. We identified 126 genes through ATAC-seq, including PPARA, TNRC6B, NEDD1, and FKBP5, that exhibited differential expression patterns during muscle growth. Additionally, we identified 59 transcription factors, including Foxh1, JunB, Mef2 family members (Mef2a/b/c/d), NeuroD1, and TEAD4. By examining open chromatin regions (OCRs) with significant genetic differentiation, genes such as SAV1, CACNA1H, PRKCG, and FGFR4 were found. Integrating ATAC-seq with transcriptomics and transcriptomics with proteomics, we identified differences in open chromatin regions, transcription, and protein levels of FKBP5 and SCARB2 genes in fast-growing and slow-growing Lijiang pigs. Utilizing multi-omics analysis with R packages, we jointed ATAC-seq, transcriptome, and proteome datasets, identifying enriched pathways related to glycogen metabolism and skeletal muscle cell differentiation. We pinpointed genes such as MYF6 and HABP2 that exhibit strong correlations across these diverse data types. This study provides a multi-faceted understanding of the molecular mechanisms that lead to differences in pig muscle fiber growth.

Ultralow-frequency absorption mechanism of a hybrid membrane resonator with acoustic soft boundary condition

Hybrid membrane resonator (HMR) as a typical metamaterial-based absorber with acoustic hard boundary condition (AHBC) has demonstrated excellent noise absorption abilities, but the challenge lies in achieving broadband absorption of ultralow-frequency noise in the tens of Hz to 150 Hz regime. In this research, we investigate systematically the absorption characteristics, absorption mechanisms, and casual optimality of an HMR with three openings in lower surface of the cavity, which functioned as an acoustic soft boundary condition (ASBC). Compared to the well-studied HMR with AHBC, a new absorption mechanism, which states that most energy dissipates occur in the opening region rather than in the membrane, has been found first. As a result, the HMR with ASBC can demonstrate outstanding ultralow-frequency sound absorption performance with a very small thickness, and the full width at half maximum of the HMR can be enlarged over 7 times. Furthermore, the causal inequalities of the absorbers with ideal AHBC and ASBC are derived based on the Cauchy integral and causality principle. The causal optimality of the proposed absorber is also achieved. This research provides valuable guidelines for the design of excellent ultralow-frequency sound absorbers which could contribute to solving the major issue of noise reduction.

Thermostability and activity improvement in l-threonine aldolase through targeted mutations in V-shaped subunit

l-threonine aldolase (LTA) catalyzes the synthesis of β-hydroxy-α-amino acids, which are important chiral intermediates widely used in the fields of pharmaceuticals and pesticides. However, the limited thermostability of LTA hinders its industrial application. Furthermore, the trade-off between thermostability and activity presents a challenge in the thermostability engineering of this enzyme. This study proposes a strategy to regulate the rigidity of LTA's V-shaped subunit by modifying its opening and hinge regions, distant from the active center, aiming to mitigate the trade-off. With LTA from Bacillus nealsonii as targeted enzyme, a total of 25 residues in these two regions were investigated by directed evolution. Finally, mutant G85A/M207L/A12C was obtained, showing significantly enhanced thermostability with a 20 °C increase in T5060 to 66 °C, and specific activity elevated by 34 % at the optimum temperature. Molecular dynamics simulations showed that the newly formed hydrophobicity and hydrogen bonds improved the thermostability and boosted proton transfer efficiency. This work enhances the thermostability of LTA while preventing the loss of activity. It opens new avenues for the thermostability engineering of other industrially relevant enzymes with active center located at the interface of subunits or domains.

High-latitude coronal mass ejections on the young solar-like star AB Dor

ABSTRACT AB Dor is a young solar-type star with a surface large-scale magnetic field $10^2$ to $10^3$ times stronger than the that of the Sun. Although strong magnetic fields are thought to inhibit coronal mass ejections (CMEs), dimming signatures typically associated with an eruptive CME were recently observed in AB Dor. The uninterrupted, long-duration dimming signal suggests that a CME took place at a high latitude, where it remained in view as the star rotates. A high-latitude CME is also consistent with observations that indicate that AB Dor hosts polar active regions. To investigate magnetic confinement in AB Dor, we conduct a parametric modelling study of 21 CMEs at latitudes ${\sim} 60^\circ$, varying the location, mass, and magnetic field strength of an injected flux rope. 12 models had the flux rope located in an open magnetic field region, while the remaining nine were in a closed region. Results show that CMEs in open-field regions are in general more likely to erupt. The four eruptive CMEs from closed regions had high free magnetic energies ${\gtrsim} 3\times 10^{35}$ erg, and 10 CMEs predominantly from the closed-field regions (8/10) were confined. CMEs in closed-field regions exhibited lower kinetic energies, since part of the CME energy was expended to overcome magnetic tension and break open the overlying field. In conclusion our work suggests that eruptive CMEs in AB Dor may occur in high-latitude regions of open magnetic field, as the magnetic tension in such regions does not significantly inhibit the eruption.