Synthetic speech detection is an essential task in the field of voice security,aimed at identifying deceptive voice attacks generated by text-to-speech(TTS)systems or voice conversion(VC)systems.In this paper,we propo...Synthetic speech detection is an essential task in the field of voice security,aimed at identifying deceptive voice attacks generated by text-to-speech(TTS)systems or voice conversion(VC)systems.In this paper,we propose a synthetic speech detection model called TFTransformer,which integrates both local and global features to enhance detection capabilities by effectively modeling local and global dependencies.Structurally,the model is divided into two main components:a front-end and a back-end.The front-end of the model uses a combination of SincLayer and two-dimensional(2D)convolution to extract high-level feature maps(HFM)containing local dependency of the input speech signals.The back-end uses time-frequency Transformer module to process these feature maps and further capture global dependency.Furthermore,we propose TFTransformer-SE,which incorporates a channel attention mechanism within the 2D convolutional blocks.This enhancement aims to more effectively capture local dependencies,thereby improving the model’s performance.The experiments were conducted on the ASVspoof 2021 LA dataset,and the results showed that the model achieved an equal error rate(EER)of 3.37%without data augmentation.Additionally,we evaluated the model using the ASVspoof 2019 LA dataset,achieving an EER of 0.84%,also without data augmentation.This demonstrates that combining local and global dependencies in the time-frequency domain can significantly improve detection accuracy.展开更多
GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a ...GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.展开更多
Human motion modeling is a core technology in computer animation,game development,and humancomputer interaction.In particular,generating natural and coherent in-between motion using only the initial and terminal frame...Human motion modeling is a core technology in computer animation,game development,and humancomputer interaction.In particular,generating natural and coherent in-between motion using only the initial and terminal frames remains a fundamental yet unresolved challenge.Existing methods typically rely on dense keyframe inputs or complex prior structures,making it difficult to balance motion quality and plausibility under conditions such as sparse constraints,long-term dependencies,and diverse motion styles.To address this,we propose a motion generation framework based on a frequency-domain diffusion model,which aims to better model complex motion distributions and enhance generation stability under sparse conditions.Our method maps motion sequences to the frequency domain via the Discrete Cosine Transform(DCT),enabling more effective modeling of low-frequency motion structures while suppressing high-frequency noise.A denoising network based on self-attention is introduced to capture long-range temporal dependencies and improve global structural awareness.Additionally,a multi-objective loss function is employed to jointly optimize motion smoothness,pose diversity,and anatomical consistency,enhancing the realism and physical plausibility of the generated sequences.Comparative experiments on the Human3.6M and LaFAN1 datasets demonstrate that our method outperforms state-of-the-art approaches across multiple performance metrics,showing stronger capabilities in generating intermediate motion frames.This research offers a new perspective and methodology for human motion generation and holds promise for applications in character animation,game development,and virtual interaction.展开更多
The precise tuning of magnetic nanoparticle size and magnetic domains,thereby shaping magnetic properties.However,the dynamic evolution mechanisms of magnetic domain configurations in relation to electromagnetic(EM)at...The precise tuning of magnetic nanoparticle size and magnetic domains,thereby shaping magnetic properties.However,the dynamic evolution mechanisms of magnetic domain configurations in relation to electromagnetic(EM)attenuation behavior remain poorly understood.To address this gap,a thermodynamically controlled periodic coordination strategy is proposed to achieve precise modulation of magnetic nanoparticle spacing.This approach unveils the evolution of magnetic domain configurations,progressing from individual to coupled and ultimately to crosslinked domain configurations.A unique magnetic coupling phenomenon surpasses the Snoek limit in low-frequency range,which is observed through micromagnetic simulation.The crosslinked magnetic configuration achieves effective low-frequency EM wave absorption at 3.68 GHz,encompassing nearly the entire C-band.This exceptional magnetic interaction significantly enhances radar camouflage and thermal insulation properties.Additionally,a robust gradient metamaterial design extends coverage across the full band(2–40 GHz),effectively mitigating the impact of EM pollution on human health and environment.This comprehensive study elucidates the evolution mechanisms of magnetic domain configurations,addresses gaps in dynamic magnetic modulation,and provides novel insights for the development of high-performance,low-frequency EM wave absorption materials.展开更多
Lithium niobate(LN)has remained at the forefront of academic research and industrial applications due to its rich material properties,which include second-order nonlinear optic,electro-optic,and piezoelectric properti...Lithium niobate(LN)has remained at the forefront of academic research and industrial applications due to its rich material properties,which include second-order nonlinear optic,electro-optic,and piezoelectric properties.A further aspect of LN’s versatility stems from the ability to engineer ferroelectric domains with micro and even nano-scale precision in LN,which provides an additional degree of freedom to design acoustic and optical devices with improved performance and is only possible in a handful of other materials.In this review paper,we provide an overview of the domain engineering techniques developed for LN,their principles,and the typical domain size and pattern uniformity they provide,which is important for devices that require high-resolution domain patterns with good reproducibility.It also highlights each technique's benefits,limitations,and adaptability for an application,along with possible improvements and future advancement prospects.Further,the review provides a brief overview of domain visualization methods,which is crucial to gain insights into domain quality/shape and explores the adaptability of the proposed domain engineering methodologies for the emerging thin-film lithium niobate on an insulator platform,which creates opportunities for developing the next generation of compact and scalable photonic integrated circuits and high frequency acoustic devices.展开更多
The cobalt-free Mn-based Li-rich layered oxide material has the advantages of low cost,high energy density,and good performance at low temperatures,and is the promising choice for energy storage batteries.However,the ...The cobalt-free Mn-based Li-rich layered oxide material has the advantages of low cost,high energy density,and good performance at low temperatures,and is the promising choice for energy storage batteries.However,the long-cycling stability of batteries needs to be improved.Herein,the Mn-based Li-rich cathode materials with small amounts of Li2 MnO3 crystal domains and gradient doping of Al and Ti elements from the surface to the bulk have been developed to improve the structure and interface stability.Then the batteries with a high energy density of 600 Wh kg^(-1),excellent capacity retention of 99.7%with low voltage decay of 0.03 mV cycle^(-1) after 800 cycles,and good rates performances can be achieved.Therefore,the structure and cycling stability of low voltage Mn-based Li-rich cathode materials can be significantly improved by the bulk structure design and interface regulation,and this work has paved the way for developing low-cost and high-energy Mn-based energy storage batteries with long lifetime.展开更多
Obtaining high magnetic properties in high Ce-content magnets is essential to expand the widespread application of low-cost magnets.In this study,high Ce-content magnets with up to 45%Ce substitution for Nd were prepa...Obtaining high magnetic properties in high Ce-content magnets is essential to expand the widespread application of low-cost magnets.In this study,high Ce-content magnets with up to 45%Ce substitution for Nd were prepared by combining the single/dual/multi-main-phase processes with the Dy-containing grain boundary diffusion process(GBDP).The effects of base magnets with different Ce distributions on GBDP were systematically investigated.Magnetic properties and micro structure analysis reveal that high-performance multi-main-phase(MMP)diffused magnets with remanence(Br)up to 12.52 kGs,coercivity up to 16.08 kOe,and maximum magnetic energy product up to 36.44 MGOe are obtained,which is attributed to the regulation of Ce by the MMP process,and the optimization of microstructure by Gd-Cu alloy.Meanwhile,the diffusion efficiency is significantly improved because of Ce being restricted to the grain core,which promotes the formation of a continuous structure at the grain boundaries,and the formation of a continuous multilayer shell grain structure with high anisotropy field,while the Br of the diffused magnet is maintained.Besides,magnetic domain analysis shows that the MMP diffused magnet effectively suppresses the nucleation of demagnetized domains and enhances the pinning effect of domain walls.The study establishes an experimental foundation for the development of sintered high Ce-content magnets showcasing superior performance.展开更多
The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurodegenerative diseases.Pharmacolo...The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurodegenerative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effectively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC_(50))of 0.478 mM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.展开更多
Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.N...Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prog-nosis in several types of tumors.Methods:We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells.We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer.The development of colorectal tumors were investigated using post-necropsy quantification,immunohistochemistry,and enzyme-linked immunosorbent assay(ELISA).Results:Compared with wild-type(WT)control mice,NSD2^(fl/fl)-Vil1-Cre mice exhib-ited significantly decreased tumor numbers,histopathological changes,and cytokine expression in colorectal tumors.Conclusions:Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.展开更多
To avoid the laborious annotation process for dense prediction tasks like semantic segmentation,unsupervised domain adaptation(UDA)methods have been proposed to leverage the abundant annotations from a source domain,s...To avoid the laborious annotation process for dense prediction tasks like semantic segmentation,unsupervised domain adaptation(UDA)methods have been proposed to leverage the abundant annotations from a source domain,such as virtual world(e.g.,3D games),and adapt models to the target domain(the real world)by narrowing the domain discrepancies.However,because of the large domain gap,directly aligning two distinct domains without considering the intermediates leads to inefficient alignment and inferior adaptation.To address this issue,we propose a novel learnable evolutionary Category Intermediates(CIs)guided UDA model named Leci,which enables the information transfer between the two domains via two processes,i.e.,Distilling and Blending.Starting from a random initialization,the CIs learn shared category-wise semantics automatically from two domains in the Distilling process.Then,the learned semantics in the CIs are sent back to blend the domain features through a residual attentive fusion(RAF)module,such that the categorywise features of both domains shift towards each other.As the CIs progressively and consistently learn from the varying feature distributions during training,they are evolutionary to guide the model to achieve category-wise feature alignment.Experiments on both GTA5 and SYNTHIA datasets demonstrate Leci's superiority over prior representative methods.展开更多
The real-time monitoring of fracture propagation during hydraulic fracturing is crucial for obtaining a deeper understanding of fracture morphology and optimizing hydraulic fracture designs.Accurate measurements of ke...The real-time monitoring of fracture propagation during hydraulic fracturing is crucial for obtaining a deeper understanding of fracture morphology and optimizing hydraulic fracture designs.Accurate measurements of key fracture parameters,such as the fracture height and width,are particularly important to ensure efficient oilfield development and precise fracture diagnosis.This study utilized the optical frequency domain reflectometer(OFDR)technique in physical simulation experiments to monitor fractures during indoor true triaxial hydraulic fracturing experiments.The results indicate that the distributed fiber optic strain monitoring technology can efficiently capture the initiation and expansion of fractures.In horizontal well monitoring,the fiber strain waterfall plot can be used to interpret the fracture width,initiation location,and expansion speed.The fiber response can be divided into three stages:strain contraction convergence,strain band formation,and postshutdown strain rate reversal.When the fracture does not contact the fiber,a dual peak strain phenomenon occurs in the fiber and gradually converges as the fracture approaches.During vertical well monitoring in adjacent wells,within the effective monitoring range of the fiber,the axial strain produced by the fiber can represent the fracture height with an accuracy of 95.6%relative to the actual fracture height.This study provides a new perspective on real-time fracture monitoring.The response patterns of fiber-induced strain due to fractures can help us better understand and assess the dynamic fracture behavior,offering significant value for the optimization of oilfield development and fracture diagnostic techniques.展开更多
AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.展开更多
The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to b...The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.展开更多
The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the bloo...The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.展开更多
Lithium-ion capacitors(LICs)combine the high power dens-ity of electrical double-layer capacitors with the high energy density of lithium-ion batteries.However,they face practical limitations due to the narrow operati...Lithium-ion capacitors(LICs)combine the high power dens-ity of electrical double-layer capacitors with the high energy density of lithium-ion batteries.However,they face practical limitations due to the narrow operating voltage window of their activated carbon(AC)cathodes.We report a scalable thermal treatment strategy to develop high-voltage-tolerant AC cathodes.Through controlled thermal treatment of commer-cial activated carbon(Raw-AC)under a H_(2)/Ar atmosphere at 400-800℃,the targeted reduction of degradation-prone functional groups can be achieved while preserving the critical pore structure and increasing graph-itic microcrystalline ordering.The AC treated at 400℃(HAC-400)had a significant increase in specific capacity(96.0 vs.75.1 mAh/g at 0.05 A/g)and better rate capability(61.1 vs.36.1 mAh/g at 5 A/g)in half-cell LICs,along with an 83.5%capacity retention over 7400 cycles within an extended voltage range of 2.0-4.2 V in full-cell LICs.Scalability was demonstrated by a 120 g batch production,enabling fabrication of pouch-type LICs with commercial hard carbon anodes that delivered a higher energy density of 28.3 Wh/kg at 1 C,and a peak power density of 12.1 kW/kg compared to devices using raw AC.This simple,industry-compatible approach may be used for producing ad-vanced cathode materials for practical high-performance LICs.展开更多
In this paper,the Paley-Wiener theorem is extended to the analytic function spaces with general weights.We first generalize the theorem to weighted Hardy spaces Hp(0<p<∞)on tube domains by constructing a sequen...In this paper,the Paley-Wiener theorem is extended to the analytic function spaces with general weights.We first generalize the theorem to weighted Hardy spaces Hp(0<p<∞)on tube domains by constructing a sequence of L^(1)functions converging to the given function and verifying their representation in the form of Fourier transform to establish the desired result of the given function.Applying this main result,we further generalize the Paley-Wiener theorem for band-limited functions to the analytic function spaces L^(p)(0<p<∞)with general weights.展开更多
Pb(Zr,Ti)O_(3)-Pb(Zn_(1/3)Nb_(2/3))O_(3) (PZT-PZN) based ceramics, as important piezoelectric materials, have a wide range of applications in fields such as sensors and actuators, thus the optimization of their piezoe...Pb(Zr,Ti)O_(3)-Pb(Zn_(1/3)Nb_(2/3))O_(3) (PZT-PZN) based ceramics, as important piezoelectric materials, have a wide range of applications in fields such as sensors and actuators, thus the optimization of their piezoelectric properties has been a hot research topic. This study investigated the effects of phase boundary engineering and domain engineering on (1-x)[0.8Pb(Zr_(0.5)Ti_(0.5))O_(3)-0.2Pb(Zn_(1/3)Nb_(2/3))O_(3)]-xBi(Zn_(0.5)Ti_(0.5))O_(3) ((1-x)(0.8PZT-0.2PZN)- xBZT) ceramic to obtain excellent piezoelectric properties. The crystal phase structure and microstructure of ceramic samples were characterized. The results showed that all samples had a pure perovskite structure, and the addition of BZT gradually increased the grain size. The addition of BZT caused a phase transition in ceramic samples from the morphotropic phase boundary (MPB) towards the tetragonal phase region, which is crucial for optimizing piezoelectric properties. By adjusting content of BZT and precisely controlling position of the phase boundary, the piezoelectric performance can be optimized. Domain structure is one of the key factors affecting piezoelectric performance. By using domain engineering techniques to optimize grain size and domain size, piezoelectric properties of ceramic samples have been significantly improved. Specifically, excellent piezoelectric properties (piezoelectric constant d_(33)=320 pC/N, electromechanical coupling factor kp=0.44) were obtained simultaneously for x=0.08. Based on experimental results and theoretical analysis, influence mechanisms of phase boundary engineering and domain engineering on piezoelectric properties were explored. The study shows that addition of BZT not only promotes grain growth, but also optimizes the domain structure, enabling the polarization reversal process easier, thereby improving piezoelectric properties. These research results not only provide new ideas for the design of high-performance piezoelectric ceramics, but also lay a theoretical foundation for development of related electronic devices.展开更多
In this paper,we give a complete characterization of all self-adjoint domains of odd order differential operators on two intervals.These two intervals with all four endpoints are singular(one endpoint of each interval...In this paper,we give a complete characterization of all self-adjoint domains of odd order differential operators on two intervals.These two intervals with all four endpoints are singular(one endpoint of each interval is singular or all four endpoints are regulars are the special cases).And these extensions yield"new"self-adjoint operators,which involve interactions between the two intervals.展开更多
基金supported by project ZR2022MF330 supported by Shandong Provincial Natural Science Foundationthe National Natural Science Foundation of China under Grant No.61701286.
文摘Synthetic speech detection is an essential task in the field of voice security,aimed at identifying deceptive voice attacks generated by text-to-speech(TTS)systems or voice conversion(VC)systems.In this paper,we propose a synthetic speech detection model called TFTransformer,which integrates both local and global features to enhance detection capabilities by effectively modeling local and global dependencies.Structurally,the model is divided into two main components:a front-end and a back-end.The front-end of the model uses a combination of SincLayer and two-dimensional(2D)convolution to extract high-level feature maps(HFM)containing local dependency of the input speech signals.The back-end uses time-frequency Transformer module to process these feature maps and further capture global dependency.Furthermore,we propose TFTransformer-SE,which incorporates a channel attention mechanism within the 2D convolutional blocks.This enhancement aims to more effectively capture local dependencies,thereby improving the model’s performance.The experiments were conducted on the ASVspoof 2021 LA dataset,and the results showed that the model achieved an equal error rate(EER)of 3.37%without data augmentation.Additionally,we evaluated the model using the ASVspoof 2019 LA dataset,achieving an EER of 0.84%,also without data augmentation.This demonstrates that combining local and global dependencies in the time-frequency domain can significantly improve detection accuracy.
基金partially supported by grants PID2020-115096RB-I00 and PID2023-148273NB-I00 from Ministerio de Ciencia y Universidad (MICIU/AEI)(to EMS)。
文摘GEMIN5 is a predominantly cytoplasmic multifunctional protein, known to be involved in recognizing snRNAs through its WD40 repeats domain placed at the N-terminus. A dimerization domain in the middle region acts as a hub for protein–protein interaction, while a non-canonical RNA-binding site is placed towards the C-terminus. The singular organization of structural domains present in GEMIN5 enables this protein to perform multiple functions through its ability to interact with distinct partners, both RNAs and proteins. This protein exerts a different role in translation regulation depending on its physiological state, such that while GEMIN5 down-regulates global RNA translation, the C-terminal half of the protein promotes translation of its mRNA. Additionally, GEMIN5 is responsible for the preferential partitioning of mRNAs into polysomes. Besides selective translation, GEMIN5 forms part of distinct ribonucleoprotein complexes, reflecting the dynamic organization of macromolecular complexes in response to internal and external signals. In accordance with its contribution to fundamental cellular processes, recent reports described clinical loss of function mutants suggesting that GEMIN5 deficiency is detrimental to cell growth and survival. Remarkably, patients carrying GEMIN5 biallelic variants suffer from neurodevelopmental delay, hypotonia, and cerebellar ataxia. Molecular analyses of individual variants, which are defective in protein dimerization, display decreased levels of ribosome association, reinforcing the involvement of the protein in translation regulation. Importantly, the number of clinical variants and the phenotypic spectrum associated with GEMIN5 disorders is increasing as the knowledge of the protein functions and the pathways linked to its activity augments. Here we discuss relevant advances concerning the functional and structural features of GEMIN5 and its separate domains in RNA-binding, protein interactome, and translation regulation, and how these data can help to understand the involvement of protein malfunction in clinical variants found in patients developing neurodevelopmental disorders.
基金supported by the National Natural Science Foundation of China(Grant No.72161034).
文摘Human motion modeling is a core technology in computer animation,game development,and humancomputer interaction.In particular,generating natural and coherent in-between motion using only the initial and terminal frames remains a fundamental yet unresolved challenge.Existing methods typically rely on dense keyframe inputs or complex prior structures,making it difficult to balance motion quality and plausibility under conditions such as sparse constraints,long-term dependencies,and diverse motion styles.To address this,we propose a motion generation framework based on a frequency-domain diffusion model,which aims to better model complex motion distributions and enhance generation stability under sparse conditions.Our method maps motion sequences to the frequency domain via the Discrete Cosine Transform(DCT),enabling more effective modeling of low-frequency motion structures while suppressing high-frequency noise.A denoising network based on self-attention is introduced to capture long-range temporal dependencies and improve global structural awareness.Additionally,a multi-objective loss function is employed to jointly optimize motion smoothness,pose diversity,and anatomical consistency,enhancing the realism and physical plausibility of the generated sequences.Comparative experiments on the Human3.6M and LaFAN1 datasets demonstrate that our method outperforms state-of-the-art approaches across multiple performance metrics,showing stronger capabilities in generating intermediate motion frames.This research offers a new perspective and methodology for human motion generation and holds promise for applications in character animation,game development,and virtual interaction.
基金supported by the National Natural Science Foundation of China(22265021,52231007,and 12327804)the Aeronautical Science Foundation of China(2020Z056056003)Jiangxi Provincial Natural Science Foundation(20232BAB212004).
文摘The precise tuning of magnetic nanoparticle size and magnetic domains,thereby shaping magnetic properties.However,the dynamic evolution mechanisms of magnetic domain configurations in relation to electromagnetic(EM)attenuation behavior remain poorly understood.To address this gap,a thermodynamically controlled periodic coordination strategy is proposed to achieve precise modulation of magnetic nanoparticle spacing.This approach unveils the evolution of magnetic domain configurations,progressing from individual to coupled and ultimately to crosslinked domain configurations.A unique magnetic coupling phenomenon surpasses the Snoek limit in low-frequency range,which is observed through micromagnetic simulation.The crosslinked magnetic configuration achieves effective low-frequency EM wave absorption at 3.68 GHz,encompassing nearly the entire C-band.This exceptional magnetic interaction significantly enhances radar camouflage and thermal insulation properties.Additionally,a robust gradient metamaterial design extends coverage across the full band(2–40 GHz),effectively mitigating the impact of EM pollution on human health and environment.This comprehensive study elucidates the evolution mechanisms of magnetic domain configurations,addresses gaps in dynamic magnetic modulation,and provides novel insights for the development of high-performance,low-frequency EM wave absorption materials.
基金supported by the Australian Research Council Centre of Excellence in Optical Microcombs for Breakthrough Science COMBS(CE230100006)the Australian Research Council grants DP220100488 and DE230100964funded by the Australian Government.
文摘Lithium niobate(LN)has remained at the forefront of academic research and industrial applications due to its rich material properties,which include second-order nonlinear optic,electro-optic,and piezoelectric properties.A further aspect of LN’s versatility stems from the ability to engineer ferroelectric domains with micro and even nano-scale precision in LN,which provides an additional degree of freedom to design acoustic and optical devices with improved performance and is only possible in a handful of other materials.In this review paper,we provide an overview of the domain engineering techniques developed for LN,their principles,and the typical domain size and pattern uniformity they provide,which is important for devices that require high-resolution domain patterns with good reproducibility.It also highlights each technique's benefits,limitations,and adaptability for an application,along with possible improvements and future advancement prospects.Further,the review provides a brief overview of domain visualization methods,which is crucial to gain insights into domain quality/shape and explores the adaptability of the proposed domain engineering methodologies for the emerging thin-film lithium niobate on an insulator platform,which creates opportunities for developing the next generation of compact and scalable photonic integrated circuits and high frequency acoustic devices.
基金supported by the National Key R&D Program of China(No.2022YFB2404400)the National Natural Science Foundation of China(Nos.U23A20577,52372168,92263206 and 21975006)+1 种基金the“The Youth Beijing Scholars program”(No.PXM2021_014204_000023)the Beijing Natural Science Foundation(Nos.2222001 and KM202110005009).
文摘The cobalt-free Mn-based Li-rich layered oxide material has the advantages of low cost,high energy density,and good performance at low temperatures,and is the promising choice for energy storage batteries.However,the long-cycling stability of batteries needs to be improved.Herein,the Mn-based Li-rich cathode materials with small amounts of Li2 MnO3 crystal domains and gradient doping of Al and Ti elements from the surface to the bulk have been developed to improve the structure and interface stability.Then the batteries with a high energy density of 600 Wh kg^(-1),excellent capacity retention of 99.7%with low voltage decay of 0.03 mV cycle^(-1) after 800 cycles,and good rates performances can be achieved.Therefore,the structure and cycling stability of low voltage Mn-based Li-rich cathode materials can be significantly improved by the bulk structure design and interface regulation,and this work has paved the way for developing low-cost and high-energy Mn-based energy storage batteries with long lifetime.
基金Project supported by the National Key Research and Development Program of China(2021YFB3502803)The"Pioneer"and"Leading Goose"R&D program of Zhejiang(2022C01020)+3 种基金Science and Technology Program of Zhejiang Province(2024C01145)The Key Research and Development Program of Ningbo City(2023Z093)Kunpeng Plan of Zhejiang ProvinceNingbo Top Talent Program。
文摘Obtaining high magnetic properties in high Ce-content magnets is essential to expand the widespread application of low-cost magnets.In this study,high Ce-content magnets with up to 45%Ce substitution for Nd were prepared by combining the single/dual/multi-main-phase processes with the Dy-containing grain boundary diffusion process(GBDP).The effects of base magnets with different Ce distributions on GBDP were systematically investigated.Magnetic properties and micro structure analysis reveal that high-performance multi-main-phase(MMP)diffused magnets with remanence(Br)up to 12.52 kGs,coercivity up to 16.08 kOe,and maximum magnetic energy product up to 36.44 MGOe are obtained,which is attributed to the regulation of Ce by the MMP process,and the optimization of microstructure by Gd-Cu alloy.Meanwhile,the diffusion efficiency is significantly improved because of Ce being restricted to the grain core,which promotes the formation of a continuous structure at the grain boundaries,and the formation of a continuous multilayer shell grain structure with high anisotropy field,while the Br of the diffused magnet is maintained.Besides,magnetic domain analysis shows that the MMP diffused magnet effectively suppresses the nucleation of demagnetized domains and enhances the pinning effect of domain walls.The study establishes an experimental foundation for the development of sintered high Ce-content magnets showcasing superior performance.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82101417,81920108017,and 82130036)the STI2030-Major Projects(Project No.:2022ZD0211800)+2 种基金Jiangsu Province Key Medical Discipline(Grant No.:ZDXK202216)the Key Research and Development Program of Jiangsu Province of China(Program No.:BE2020620)Nanjing Medical Science and technology development Foundation,China(Grant No.:YKK20061).
文摘The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurodegenerative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effectively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC_(50))of 0.478 mM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.
基金supported by the National Key Research and Development Program of China (2022YFF0710705)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-0 13)+2 种基金funding support from the Special Research Fund for Central UniversitiesPeking Union Medical College (3332022182)the 111 Project (B20095)
文摘Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prog-nosis in several types of tumors.Methods:We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells.We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer.The development of colorectal tumors were investigated using post-necropsy quantification,immunohistochemistry,and enzyme-linked immunosorbent assay(ELISA).Results:Compared with wild-type(WT)control mice,NSD2^(fl/fl)-Vil1-Cre mice exhib-ited significantly decreased tumor numbers,histopathological changes,and cytokine expression in colorectal tumors.Conclusions:Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.
基金Australian Research Council Project(FL-170100117).
文摘To avoid the laborious annotation process for dense prediction tasks like semantic segmentation,unsupervised domain adaptation(UDA)methods have been proposed to leverage the abundant annotations from a source domain,such as virtual world(e.g.,3D games),and adapt models to the target domain(the real world)by narrowing the domain discrepancies.However,because of the large domain gap,directly aligning two distinct domains without considering the intermediates leads to inefficient alignment and inferior adaptation.To address this issue,we propose a novel learnable evolutionary Category Intermediates(CIs)guided UDA model named Leci,which enables the information transfer between the two domains via two processes,i.e.,Distilling and Blending.Starting from a random initialization,the CIs learn shared category-wise semantics automatically from two domains in the Distilling process.Then,the learned semantics in the CIs are sent back to blend the domain features through a residual attentive fusion(RAF)module,such that the categorywise features of both domains shift towards each other.As the CIs progressively and consistently learn from the varying feature distributions during training,they are evolutionary to guide the model to achieve category-wise feature alignment.Experiments on both GTA5 and SYNTHIA datasets demonstrate Leci's superiority over prior representative methods.
基金supported by the National Natural Science Foundation of China(Grant No.52104060)the Natural Science Foundation of Shandong Province,China(Grant No.ZR2021QE015).
文摘The real-time monitoring of fracture propagation during hydraulic fracturing is crucial for obtaining a deeper understanding of fracture morphology and optimizing hydraulic fracture designs.Accurate measurements of key fracture parameters,such as the fracture height and width,are particularly important to ensure efficient oilfield development and precise fracture diagnosis.This study utilized the optical frequency domain reflectometer(OFDR)technique in physical simulation experiments to monitor fractures during indoor true triaxial hydraulic fracturing experiments.The results indicate that the distributed fiber optic strain monitoring technology can efficiently capture the initiation and expansion of fractures.In horizontal well monitoring,the fiber strain waterfall plot can be used to interpret the fracture width,initiation location,and expansion speed.The fiber response can be divided into three stages:strain contraction convergence,strain band formation,and postshutdown strain rate reversal.When the fracture does not contact the fiber,a dual peak strain phenomenon occurs in the fiber and gradually converges as the fracture approaches.During vertical well monitoring in adjacent wells,within the effective monitoring range of the fiber,the axial strain produced by the fiber can represent the fracture height with an accuracy of 95.6%relative to the actual fracture height.This study provides a new perspective on real-time fracture monitoring.The response patterns of fiber-induced strain due to fractures can help us better understand and assess the dynamic fracture behavior,offering significant value for the optimization of oilfield development and fracture diagnostic techniques.
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
基金supported by the TARCC,Welch Foundation Award(I-1724)the Decherd Foundationthe Pape Adams Foundation,NIH grants NS092616,NS127375,NS117065,NS111776。
文摘The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following insults.Whether targeting this pathway is beneficial to brain injury remains unclear.In this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral deficits.Pharmacological inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology domain.Mechanistically,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin pathway.These findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No.82104412(to TD)Shaanxi Provincial Key R&D Program,No.2023-YBSF-165(to TD)+1 种基金the Natural Science Foundation of Shaanxi Department of Science and Technology,No.2018JM7022(to FM)Shaanxi Provincial Key Industry Chain Project,No.2021ZDLSF04-11(to PW)。
文摘The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.
文摘Lithium-ion capacitors(LICs)combine the high power dens-ity of electrical double-layer capacitors with the high energy density of lithium-ion batteries.However,they face practical limitations due to the narrow operating voltage window of their activated carbon(AC)cathodes.We report a scalable thermal treatment strategy to develop high-voltage-tolerant AC cathodes.Through controlled thermal treatment of commer-cial activated carbon(Raw-AC)under a H_(2)/Ar atmosphere at 400-800℃,the targeted reduction of degradation-prone functional groups can be achieved while preserving the critical pore structure and increasing graph-itic microcrystalline ordering.The AC treated at 400℃(HAC-400)had a significant increase in specific capacity(96.0 vs.75.1 mAh/g at 0.05 A/g)and better rate capability(61.1 vs.36.1 mAh/g at 5 A/g)in half-cell LICs,along with an 83.5%capacity retention over 7400 cycles within an extended voltage range of 2.0-4.2 V in full-cell LICs.Scalability was demonstrated by a 120 g batch production,enabling fabrication of pouch-type LICs with commercial hard carbon anodes that delivered a higher energy density of 28.3 Wh/kg at 1 C,and a peak power density of 12.1 kW/kg compared to devices using raw AC.This simple,industry-compatible approach may be used for producing ad-vanced cathode materials for practical high-performance LICs.
基金Supported by the National Natural Science Foundation of China(12301101)the Guangdong Basic and Applied Basic Research Foundation(2022A1515110019 and 2020A1515110585)。
文摘In this paper,the Paley-Wiener theorem is extended to the analytic function spaces with general weights.We first generalize the theorem to weighted Hardy spaces Hp(0<p<∞)on tube domains by constructing a sequence of L^(1)functions converging to the given function and verifying their representation in the form of Fourier transform to establish the desired result of the given function.Applying this main result,we further generalize the Paley-Wiener theorem for band-limited functions to the analytic function spaces L^(p)(0<p<∞)with general weights.
基金National Natural Science Foundation of China (52202139, 52072178)。
文摘Pb(Zr,Ti)O_(3)-Pb(Zn_(1/3)Nb_(2/3))O_(3) (PZT-PZN) based ceramics, as important piezoelectric materials, have a wide range of applications in fields such as sensors and actuators, thus the optimization of their piezoelectric properties has been a hot research topic. This study investigated the effects of phase boundary engineering and domain engineering on (1-x)[0.8Pb(Zr_(0.5)Ti_(0.5))O_(3)-0.2Pb(Zn_(1/3)Nb_(2/3))O_(3)]-xBi(Zn_(0.5)Ti_(0.5))O_(3) ((1-x)(0.8PZT-0.2PZN)- xBZT) ceramic to obtain excellent piezoelectric properties. The crystal phase structure and microstructure of ceramic samples were characterized. The results showed that all samples had a pure perovskite structure, and the addition of BZT gradually increased the grain size. The addition of BZT caused a phase transition in ceramic samples from the morphotropic phase boundary (MPB) towards the tetragonal phase region, which is crucial for optimizing piezoelectric properties. By adjusting content of BZT and precisely controlling position of the phase boundary, the piezoelectric performance can be optimized. Domain structure is one of the key factors affecting piezoelectric performance. By using domain engineering techniques to optimize grain size and domain size, piezoelectric properties of ceramic samples have been significantly improved. Specifically, excellent piezoelectric properties (piezoelectric constant d_(33)=320 pC/N, electromechanical coupling factor kp=0.44) were obtained simultaneously for x=0.08. Based on experimental results and theoretical analysis, influence mechanisms of phase boundary engineering and domain engineering on piezoelectric properties were explored. The study shows that addition of BZT not only promotes grain growth, but also optimizes the domain structure, enabling the polarization reversal process easier, thereby improving piezoelectric properties. These research results not only provide new ideas for the design of high-performance piezoelectric ceramics, but also lay a theoretical foundation for development of related electronic devices.
基金Supported by NSFC (No.12361027)NSF of Inner Mongolia (No.2018MS01021)+1 种基金NSF of Shandong Province (No.ZR2020QA009)Science and Technology Innovation Program for Higher Education Institutions of Shanxi Province (No.2024L533)。
文摘In this paper,we give a complete characterization of all self-adjoint domains of odd order differential operators on two intervals.These two intervals with all four endpoints are singular(one endpoint of each interval is singular or all four endpoints are regulars are the special cases).And these extensions yield"new"self-adjoint operators,which involve interactions between the two intervals.
