A new mechanical structural damage feature index based on HHT

A new damage feature index is presented for the structural health monitoring based on Hilbert-Huang transform (HHT). The energy marginal spectrum of the dynamic signal is used to construct damage characteristic parameter, which can reflect the signal energy variation and benefit the structural damage detection. A sinusoidal wave with frequency change and a composite plate vibration experiment with pre-defined damage are designed to verify the effectiveness of characteristic parameter in damage detection. Results obtained from simulation and test show that the extracted non-model-based damage feature index is available and sensitive in damage detection of time-varying system.Peer Reviewe

Computing the lower and upper bounds of Laplace eigenvalue problem: by combining conforming and nonconforming finite element methods

This article is devoted to computing the lower and upper bounds of the Laplace eigenvalue problem. By using the special nonconforming finite elements, i.e., enriched Crouzeix-Raviart element and extension $Q_1^{\rm rot}$, we get the lower bound of the eigenvalue. Additionally, we also use conforming finite elements to do the postprocessing to get the upper bound of the eigenvalue. The postprocessing method need only to solve the corresponding source problems and a small eigenvalue problem if higher order postprocessing method is implemented. Thus, we can obtain the lower and upper bounds of the eigenvalues simultaneously by solving eigenvalue problem only once. Some numerical results are also presented to validate our theoretical analysis.Comment: 19 pages, 4 figure

Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn

AIMS: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by sustained high levels of pulmonary vascular resistance after birth with etiology unclear; Arterial blood oxygen saturation of Tibetan newborns at high latitudes is higher than that of Han newborns at low latitudes, suggesting that genetic adaptation may allow sufficient oxygen to confer Tibetan populations with resistance to pulmonary hypertension; We have previously identified genetic factors related to PPHN through candidate gene sequencing; In this study, we first performed whole exome sequencing in PPHN patients to screen for genetic-related factors. METHODS AND RESULTS: In this two-phase genetic study, we first sequenced the whole exome of 20 Tibetan PPHN patients and compared it with the published genome sequences of 50 healthy high-altitude Tibetanshypoxia-related genes, a total of 166 PPHN-related variants were found, of which 49% were from 43 hypoxia-related genes; considering many studies have shown that the differences in the genetic background between Tibet and Han are characterized by hypoxia-related genetic polymorphisms, so it is necessary to further verify whether the association between hypoxia-related variants and PPHN is independent of high-altitude life. During the validation phase, 237 hypoxia-related genes were sequenced in another 80 Han PPHN patients living in low altitude areas, including genes at the discovery stage and known hypoxia tolerance, of which 413 variants from 127 of these genes were shown to be significantly associated with PPHN.hypoxia-related genes. CONCLUSIONS: Our results indicates that the association of hypoxia-related genes with PPHN does not depend on high-altitude life, at the same time, 21 rare mutations associated with PPHN were also found, including three rare variants of the tubulin tyrosine ligase-like family member 3 gene (TTLL3:p.E317K, TTLL3:p.P777S) and the integrin subunit alpha M gene (ITGAM:p.E1071D). These novel findings provide important information on the genetic basis of PPHN

Image quality and evaluation ability of magnetic resonance imaging techniques for thyroid-associated ophthalmopathy: Dixon fat-suppression technique vs. spectral attenuated inversion recovery

PurposeWe aimed to compare two magnetic resonance imaging (MRI) techniques, Dixon and spectral attenuated inversion recovery (SPAIR) fat-suppression, in terms of image quality and suitability for evaluating thyroid-associated ophthalmopathy (TAO) lesion characteristics.MethodsThis cross-sectional, retrospective study involved 70 patients with TAO (140 eyes) who underwent orbital coronal MRI examinations, including Dixon-transverse relaxation (T2)-weighted imaging (T2WI) and SPAIR-T2WI, between 2020 and 2022. We compared the fat-suppression quality and artifacts, noise (N), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal intensity ratio (SIR) of extraocular muscles (SIR-EOM) and lacrimal glands (SIR-LG), and TAO activity evaluation efficiency.ResultsDixon-T2WI showed a higher frequency of better subjective image quality and suitability for evaluating the characteristics of TAO lesions (65.7% vs. 14.3%) than SPAIR-T2WI. Fat-suppression quality and artifact scores were lower for Dixon-T2WI than for SPAIR-T2WI (p < 0.001). The N, SNR, and CNR values, EOM-SIR, and LG-SIR were higher for orbital coronal Dixon-T2WI than for SPAIR-T2WI (all p < 0.001). Clinical activity scores (CASs) showed positive correlations with SIR. The correlation between EOM-SIR and LG-SIR of orbital coronal Dixon-T2WI with CAS was higher than that of SPAIR-T2WI (0.590 vs. 0.493, all p < 0.001; 0.340 vs. 0.295, all p < 0.01). EOM-SIR and LG-SIR of Dixon-T2WI yielded a higher area under the curve than SPAIR-T2WI for evaluating TAO activity (0.865 vs. 0.760, p < 0.001; 0.695 vs. 0.617, p = 0.017).ConclusionDixon-T2WI yields higher image quality than SPAIR-T2WI. Furthermore, it has a stronger ability to evaluate TAO inflammation than SPAIR, with higher sensitivity and specificity in active TAO staging

Co-inhibition of HDAC and MLL-menin interaction targets MLL-rearranged acute myeloid leukemia cells via disruption of DNA damage checkpoint and DNA repair.

While the aberrant translocation of the mixed-lineage leukemia (MLL) gene drives pathogenesis of acute myeloid leukemia (AML), it represents an independent predictor for poor prognosis of adult AML patients. Thus, small molecule inhibitors targeting menin-MLL fusion protein interaction have been emerging for the treatment of MLL-rearranged AML. As both inhibitors of histone deacetylase (HDAC) and menin-MLL interaction target the transcription-regulatory machinery involving epigenetic regulation of chromatin remodeling that governs the expression of genes involved in tumorigenesis, we hypothesized that these two classes of agents might interact to kill MLL-rearranged (MLL-r) AML cells. Here, we report that the combination treatment with subtoxic doses of the HDAC inhibitor chidamide and the menin-MLL interaction inhibitor MI-3 displayed a highly synergistic anti-tumor activity against human MLL-r AML cells in vitro and in vivo, but not those without this genetic aberration. Mechanistically, co-exposure to chidamide and MI-3 led to robust apoptosis in MLL-r AML cells, in association with loss of mitochondrial membrane potential and a sharp increase in ROS generation. Combined treatment also disrupted DNA damage checkpoint at the level of CHK1 and CHK2 kinases, rather than their upstream kinases (ATR and ATM), as well as DNA repair likely via homologous recombination (HR), but not non-homologous end joining (NHEJ). Genome-wide RNAseq revealed gene expression alterations involving several potential signaling pathways (e.g., cell cycle, DNA repair, MAPK, NF-κB) that might account for or contribute to the mechanisms of action underlying anti-leukemia activity of chidamide and MI-3 as a single agent and particularly in combination in MLL-r AML. Collectively, these findings provide a preclinical basis for further clinical investigation of this novel targeted strategy combining HDAC and Menin-MLL interaction inhibitors to improve therapeutic outcomes in a subset of patients with poor-prognostic MLL-r leukemia

ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism.

It is unclear whether mutations in fused in sarcoma (FUS) cause familial amyotrophic lateral sclerosis via a loss-of-function effect due to titrating FUS from the nucleus or a gain-of-function effect from cytoplasmic overabundance. To investigate this question, we generated a series of independent Caenorhabditis elegans lines expressing mutant or wild-type (WT) human FUS. We show that mutant FUS, but not WT-FUS, causes cytoplasmic mislocalization associated with progressive motor dysfunction and reduced lifespan. The severity of the mutant phenotype in C. elegans was directly correlated with the severity of the illness caused by the same mutation in humans, arguing that this model closely replicates key features of the human illness. Importantly, the mutant phenotype could not be rescued by overexpression of WT-FUS, even though WT-FUS had physiological intracellular localization, and was not recruited to the cytoplasmic mutant FUS aggregates. Our data suggest that FUS mutants cause neuronal dysfunction by a dominant gain-of-function effect related either to neurotoxic aggregates of mutant FUS in the cytoplasm or to dysfunction in its RNA-binding functions

Quantum Neuronal Sensing of Quantum Many-Body States on a 61-Qubit Programmable Superconducting Processor

Classifying many-body quantum states with distinct properties and phases of matter is one of the most fundamental tasks in quantum many-body physics. However, due to the exponential complexity that emerges from the enormous numbers of interacting particles, classifying large-scale quantum states has been extremely challenging for classical approaches. Here, we propose a new approach called quantum neuronal sensing. Utilizing a 61 qubit superconducting quantum processor, we show that our scheme can efficiently classify two different types of many-body phenomena: namely the ergodic and localized phases of matter. Our quantum neuronal sensing process allows us to extract the necessary information coming from the statistical characteristics of the eigenspectrum to distinguish these phases of matter by measuring only one qubit. Our work demonstrates the feasibility and scalability of quantum neuronal sensing for near-term quantum processors and opens new avenues for exploring quantum many-body phenomena in larger-scale systems.Comment: 7 pages, 3 figures in the main text, and 13 pages, 13 figures, and 1 table in supplementary material