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An emerging family of innate lymphoid cells (termed ILCs) has an essential role in the initiation and regulation of inflammation. However, it is still unclear how ILCs are regulated in the duration of intestinal inflammation. Here, we identify a regulatory subpopulation of ILCs (called ILCregs) that exists in the gut and harbors a unique gene identity that is distinct from that of ILCs or regulatory T cells (Tregs). During inflammatory stimulation, ILCregs can be induced in the intestine and suppress the activation of ILC1s and ILC3s via secretion of IL-10, leading to protection against innate intestinal inflammation. Moreover, TGF-ß1 is induced by ILCregs during the innate intestinal inflammation, and autocrine TGF-ß1 sustains the maintenance and expansion of ILCregs. Therefore, ILCregs play an inhibitory role in the innate immune response, favoring the resolution of intestinal inflammation.
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Colite/imunologia , Imunidade Inata , Linfócitos/citologia , Linfócitos/imunologia , Mucosa/citologia , Mucosa/imunologia , Animais , Linfócitos B/imunologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Organismos Livres de Patógenos Específicos , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta1/imunologiaRESUMO
KCTD10 belongs to the KCTD (potassiumchannel tetramerization domain) family, many members of which are associated with neuropsychiatric disorders. However, the biological function underlying the association with brain disorders remains to be explored. Here, we reveal that Kctd10 is highly expressed in neuronal progenitors and layer V neurons throughout brain development. Kctd10 deficiency triggers abnormal proliferation and differentiation of neuronal progenitors, reduced deep-layer (especially layer V) neurons, increased upper-layer neurons, and lowered brain size. Mechanistically, we screened and identified a unique KCTD10-interacting protein, KCTD13, associated with neurodevelopmental disorders. KCTD10 mediated the ubiquitination-dependent degradation of KCTD13 and KCTD10 ablation resulted in a considerable increase of KCTD13 expression in the developing cortex. KCTD13 overexpression in neuronal progenitors led to reduced proliferation and abnormal cell distribution, mirroring KCTD10 deficiency. Notably, mice with brain-specific Kctd10 knockout exhibited obvious motor deficits. This study uncovers the physiological function of KCTD10 and provides unique insights into the pathogenesis of neurodevelopmental disorders.
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Encefalopatias , Transtornos do Neurodesenvolvimento , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Animais , Camundongos , Proteínas/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Transtornos do Neurodesenvolvimento/genética , Encefalopatias/genética , Neurogênese/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismoRESUMO
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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Antivirais/farmacologia , Hidroxicolesteróis/farmacologia , Microcefalia/virologia , Infecção por Zika virus/complicações , Animais , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Imunofluorescência , Humanos , Macaca mulatta , Camundongos , Microscopia Confocal , Internalização do Vírus/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Zika virus/fisiologiaRESUMO
In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.
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Dendritos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos , Bulbo Olfatório , Olfato , Animais , Feminino , Masculino , Camundongos , Dendritos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Microtúbulos/metabolismo , Morfogênese/genética , Bulbo Olfatório/metabolismo , Olfato/fisiologiaRESUMO
We introduce perfect correlation vortices and show that the degree of coherence of any such vortex at the source is nearly statistically homogeneous and independent of the topological charge of the vortex. We demonstrate that while slowly diffracting in free space, perfect correlation vortices maintain their "perfect" vortex structure; they are capable of preserving said structure even in strong atmospheric turbulence. Structural resilience to diffraction and turbulence sets the discovered perfect vortices apart from their coherent cousins and makes them suitable for free-space optical communications.
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Scientists are increasingly paying attention to using theoretical design as a guide combined with modern in-situ characterization techniques to develop catalysts with high activity, low cost, and long-term life. The review discusses the progress of catalyst theoretical design and corresponding experiments based on three typical oxygen evolution catalytic mechanisms, including the adsorbate evolution, lattice oxygen-mediated, and unconventional bifunctional mechanisms. This work briefly describes the commonly used tools and descriptors in theory as well as the electrochemical techniques and characterizations in experiments. Our purpose is to sort out the ways to closely integrate the theoretical method and experimental verification from the perspective of reaction mechanism, and to provide some experience reference for the future development of theoretical tools and experimental technologies.
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BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder clinically characterized by combinations of autonomic failure, parkinsonism, cerebellar ataxia and pyramidal signs. Although a few genetic factors have been reported to contribute to the disease, its mutational profiles have not been systemically studied. METHODS: To address the genetic profiles of clinically diagnosed MSA patients, exome sequencing and triplet repeat detection was conducted in 205 MSA patients, including one familial case. The pathogenicity of variants was determined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: In the familial patient, a novel heterozygous COQ2 pathogenic variant (p.Ala351Thr) was identified in the MSA pedigree. In the sporadic patients, 29 pathogenic variants were revealed in 21 genes, and the PARK7 p.Ala104Thr variant was significantly associated with MSA (p = 0.0018). Moreover, burden tests demonstrated that the pathogenic variants were enriched in cerebellar ataxia-related genes in patients. Furthermore, repeat expansion analyses revealed that two patients carried the pathogenic CAG repeat expansion in the CACNA1A gene (SCA6), one patient carried the (ACAGG)exp/(ACAGG)exp expansion in RFC1 and one carried the GAA-pure expansion in FGF14 gene. CONCLUSION: In conclusion, a novel COQ2 pathogenic variant was identified in a familial MSA patient, and repeat expansions in CACNA1A, RFC1 and FGF14 gene were detected in four sporadic patients. Moreover, a PARK7 variant and the burden of pathogenic variants in cerebellar ataxia-related genes were associated with MSA.
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An in vitro diagnostic device (IVD) that is essential for the safe and effective use of a corresponding therapeutic product is commonly referred to as companion diagnostic device. Clinical trials using companion diagnostic devices (tests) together with therapies can yield the information necessary to address whether both products are safe and effective. A clinical trial ideally assesses safety and effectiveness of a therapy, where the clinical trial enrolls subjects based on the final market ready companion diagnostic test (CDx). However, such a requirement may be difficult to accomplish or impractical to achieve at the time of the clinical trial enrollment, due to unavailability of the CDx. Instead, clinical trial assay(s) (CTA), which are not the final marketable product, are often used in enrollment of patients in a clinical trial. When CTA is used for subject enrollment, a clinical bridging study provides a mechanism to bridge the clinical efficacy of the therapeutic product from CTA to CDx. This manuscript reviews some issues and challenges commonly associated with clinical bridging studies, including missing data, use of local tests for enrollment, prescreening before enrollment, and evaluation of CDx for low positive rate biomarkers, with particular focus on clinical trials using a binary endpoint and provide alternative statistical methodologies to assess effectiveness of CDx.
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Medicina de Precisão , Humanos , Biomarcadores , Medicina de Precisão/métodos , Resultado do TratamentoRESUMO
Collapsin response mediator protein 2 (CRMP2) is a member of a protein family, which is highly involved in neurodevelopment, but most of its members become heavily downregulated in adulthood. CRMP2 is an important factor in neuronal polarization, axonal formation and growth cone collapse. The protein remains expressed in adulthood, but is more region specific. CRMP2 is present in adult corpus callosum (CC) and in plastic areas like prefrontal cortex and hippocampus. CRMP2 has been implicated as one of the risk-genes for Schizophrenia (SZ). Here, a CRMP2 conditional knockout (CRMP2-cKO) mouse was used as a model of SZ to investigate how it could affect the white matter and therefore brain connectivity. Multielectrode electrophysiology (MEA) was used to study the function of corpus callosum showing an increase in conduction velocity (CV) measured as Compound Action Potentials (CAPs) in acute brain slices. Light- and electron-microscopy, specifically Serial Block-face Scanning Electron Microscopy (SBF-SEM), methods were used to study the structure of CC in CRMP2-cKO mice. A decrease in CC volume of CRMP2-cKO mice as compared to controls was observed. No differences were found in numbers nor in the size of CC oligodendrocytes (OLs). Similarly, no differences were found in myelin thickness or in node of Ranvier (NR) structure. In contrast, abnormally smaller axons were measured in the CRMP2-cKO mice. Using these state-of-the-art methods it was possible to shed light on specific parts of the dysconnectivity aspect of deletion of CRMP2 related to SZ and add details to previous findings helping further understanding the disease. This paper substantiates the white matter changes in the absence of CRMP2 and ties it to the role it plays in this complex disorder.
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Axônios , Corpo Caloso , Animais , Camundongos , Axônios/fisiologia , Encéfalo , Camundongos Knockout , Bainha de Mielina , Neurônios/metabolismoRESUMO
BACKGROUND: Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched. METHODS: A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform. RESULTS: Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males. CONCLUSIONS: We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.
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Doença de Parkinson , Medidas de Resultados Relatados pelo Paciente , Autogestão , Smartphone , Humanos , Doença de Parkinson/terapia , Masculino , Feminino , Projetos Piloto , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Fatores Sexuais , Aplicativos MóveisRESUMO
Antimony selenosulfide (Sb2(S,Se)3), featuring large absorption coefficient, excellent crystal structure stability, benign non-toxic characteristic, outstanding humidity and ultraviolet tolerability, has recently attracted enormous attention and research interest regarding its photoelectric conversion properties. However, the open-circuit voltage (Voc) for Sb2(S,Se)3-based photovoltaic devices is relatively low, especially for the device with a high power conversion efficiency (η). Herein, an innovative Se-elemental concentration gradient regulation strategy has been exploited to produce high-quality Sb2(S,Se)3 films on TiO2/CdS substrates through a thioacetamide(TA)-synergistic dual-sulfur source hydrothermal-processed method. The Se-elemental gradient distribution produces a favorable energy band structure, which suppresses the energy level barriers for hole transport and enhances the driving force for electron transport in Sb2(S,Se)3 film. This facilitates efficient charge transport/separation of photogenerated carriers and boosts significantly the Voc of Sb2(S,Se)3 photovoltaic devices. The champion TA-Sb2(S,Se)3 planar heterojunction (PHJ) solar cell displays an considerable η of 9.28% accompanied by an exciting Voc rising to 0.70 V that is currently the highest among Sb2(S,Se)3-based solar cells with efficiencies exceeding 9.0%. This research is anticipated to contribute to the preparation of high-quality Sb2(S,Se)3 thin film and the achievement of efficient inorganic Sb2(S,Se)3 PHJ photovoltaic device.
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An aerosol jet printing-enabled dual-function biosensor for the sensitive detection of pathogens using SARS-CoV-2 RNA as an example has been developed. A CRISPR-Cas13:guide-RNA complex is activated in the presence of a target RNA, leading to the collateral trans-cleavage of ssRNA probes that contain a horseradish peroxidase (HRP) tag. This, in turn, catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by HRP, resulting in a color change and electrochemical signal change. The colorimetric and electrochemical sensing protocol does not require complicated target amplification and probe immobilization and exhibits a detection sensitivity in the femtomolar range. Additionally, our biosensor demonstrates a wide dynamic range of 5 orders of magnitude. This low-cost aerosol inkjet printing technique allows for an amplification-free and integrated dual-function biosensor platform, which operates at physiological temperature and is designed for simple, rapid, and accurate point-of-care (POC) diagnostics in either low-resource settings or hospitals.
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Técnicas Biossensoriais , COVID-19 , Humanos , SARS-CoV-2 , Limite de Detecção , Colorimetria/métodos , RNA Viral , COVID-19/diagnóstico , Aerossóis e Gotículas Respiratórios , Peroxidase do Rábano Silvestre , Técnicas Biossensoriais/métodosRESUMO
BACKGROUND: Tau pathology is observed during autopsy in many patients with Parkinson's disease dementia (PDD). Positron emission tomography (PET) imaging using the tracer 18 F-florzolotau has the potential to capture tau accumulation in the living brain. OBJECTIVE: The aim was to describe the results of 18 F-florzolotau PET/CT (computed tomography) imaging in patients with PDD. METHODS: Ten patients with PDD, 9 with Parkinson's disease with normal cognition (PD-NC), and 9 age-matched healthy controls (HCs) were enrolled. Clinical assessments and 18 F-florzolotau PET/CT imaging were performed. RESULTS: 18 F-Florzolotau uptake was significantly higher in the cortical regions of patients with PDD compared with both PD-NC and HCs, especially in the temporal lobe. Notably, 18 F-florzolotau uptake in the occipital lobe of patients with PDD showed a significant correlation with cognitive impairment as reflected by Mini-Mental State Examination (MMSE) scores. CONCLUSIONS: 18 F-Florzolotau PET imaging can effectively capture the occurrence of tau pathology in patients with PDD, which was also linked to MMSE scores. © 2022 International Parkinson and Movement Disorder Society.
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Doença de Alzheimer , Demência , Doença de Parkinson , Humanos , Demência/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Proteínas tauRESUMO
Randomization is considered a safeguard against bias and a gold standard in clinical studies. To assess the generalizability of the accuracy of a model, a common approach is to randomly split a master data set into two parts: one for training and the other for testing. In this paper, we demonstrated the limitations of random split in assessing the generalizability of the accuracy of models through simulation studies. We generated three simulation data for binary or continuous endpoints, each with large sample size (n = 10,000). In each simulation scenario, we randomly split the data into two, one for training and one for testing, and then compare the performance of the model between training and testing data. All simulations were repeated 1,000 times. When random split was used, the model performance based on training and testing data behaved similarly in terms of the true positive fraction and false positive fraction for binary data and mean-squared errors for continuous data. However, when there is a time drift effect in the data, random split will result in large differences between training and testing data. As the training and testing data are similar through a random split, assessing the generalizability of the model on similar data will generate similar results. Generalizability of the accuracy of models is thus best achieved if testing is done in a distinct and independent study.
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Simulação por Computador , Humanos , Tamanho da Amostra , ViésRESUMO
WDR62 mutations that result in protein loss, truncation or single amino-acid substitutions are causative for human microcephaly, indicating critical roles in cell expansion required for brain development. WDR62 missense mutations that retain protein expression represent partial loss-of-function mutants that may therefore provide specific insights into radial glial cell processes critical for brain growth. Here we utilized CRISPR/Cas9 approaches to generate three strains of WDR62 mutant mice; WDR62 V66M/V66M and WDR62R439H/R439H mice recapitulate conserved missense mutations found in humans with microcephaly, with the third strain being a null allele (WDR62stop/stop). Each of these mutations resulted in embryonic lethality to varying degrees and gross morphological defects consistent with ciliopathies (dwarfism, anophthalmia and microcephaly). We find that WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP. As a consequence, we observe deficient recruitment of IFT88, a protein that is required for cilia formation. This underpins the maintenance of radial glia as WDR62 mutations caused premature differentiation of radial glia resulting in reduced generation of neurons and cortical thinning. These findings highlight the important role of the primary cilium in neocortical expansion and implicate ciliary dysfunction as underlying the pathology of MCPH2 patients.
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Proteínas de Ciclo Celular/metabolismo , Cílios/metabolismo , Ciliopatias/genética , Microcefalia/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neocórtex/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Anoftalmia/embriologia , Anoftalmia/genética , Anoftalmia/metabolismo , Apoptose/genética , Sistemas CRISPR-Cas , Proteínas de Ciclo Celular/genética , Células Cultivadas , Cílios/genética , Cílios/patologia , Ciliopatias/embriologia , Ciliopatias/metabolismo , Ciliopatias/patologia , Nanismo/embriologia , Nanismo/genética , Nanismo/metabolismo , Células Ependimogliais/citologia , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Fibroblastos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microcefalia/embriologia , Microcefalia/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Mutação de Sentido Incorreto , Neocórtex/embriologia , Proteínas do Tecido Nervoso/genética , Neurogênese/genética , Neuroglia/citologia , Neuroglia/metabolismo , Neurônios/metabolismo , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration. METHODS: To compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol. RESULTS: A total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P < 0.001 and 10.43 ± 1.20 cm H2O vs. 14.0 ± 3.0 cm H2O, P < 0.001, respectively). In the COPD group, the PEEP level titrated by EIT was lower than that titrated by the ARDSnet protocol (6.93 ± 1.69 cm H2O vs. 10.43 ± 1.20 cm H2O, P < 0.001), as was the global inhomogeneity (GI) index (0.397 ± 0.040 vs. 0.446 ± 0.052, P = 0.001), plateau airway pressure (16.50 ± 4.35 cm H2O vs. 20.93 ± 5.37 cm H2O, P = 0.001), dead space ventilation ratio (48.29 ± 6.78% vs. 55.14 ± 8.85%, P < 0.001), ventilation ratio (1.63 ± 0.33 vs. 1.87 ± 0.33, P < 0.001), and mechanical power (13.92 ± 2.18 J/min vs. 15.87 ± 2.53 J/min, P < 0.001). The cardiac index was higher when PEEP was treated by EIT than when it was titrated by the ARDSnet protocol (3.41 ± 0.50 L/min/m2 vs. 3.02 ± 0.43 L/min/m2, P < 0.001), as was oxygen delivery (466.40 ± 71.08 mL/min/m2 vs. 411.10 ± 69.71 mL/min/m2, P = 0.001). CONCLUSION: Titrated PEEP levels were lower in patients with ARDS with COPD than in ARDS patients without COPD. In ARDS patient comorbid with COPD, application of PEEP titrated by EIT was lower than those titrated by the ARDSnet protocol, which contributed to improvements in the ventilation ratio, mechanical energy, cardiac index, and oxygen delivery with less of an adverse impact on hemodynamics.
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Doença Pulmonar Obstrutiva Crônica , Síndrome do Desconforto Respiratório , Humanos , Impedância Elétrica , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/terapia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Tomografia Computadorizada por Raios X , OxigênioRESUMO
We demonstrate analytically and verify numerically that recently discovered, and experimentally realized, partially coherent dark and antidark beams are structurally stable on propagation in a statistically homogeneous, isotropic random medium, such as the turbulent atmosphere. The dark/antidark beams defy diffraction in free space, and they manifest themselves as dark/bright notches/bumps against an incoherent background. The structure of a bump/notch remains invariant on propagation of the beam through the random medium, while the peak amplitude of the bump/notch decays with the propagation distance in the medium at a rate dependent on the strength of the medium turbulence. We also evaluate numerically the scintillation index of such beams and show that it is significantly lower than that of generic, low-coherence Gaussian Schell-model beams. The combination of structural stability and low scintillations makes partially coherent dark/antidark beams very promising candidates for information transfer and optical communications through atmospheric turbulence.
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[This corrects the article DOI: 10.1371/journal.pgen.1007463.].
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In order to understand the incipient movement of muddy clay under different salinity conditions, three series of flume tests were performed on incipient movement of muddy clay, including tests on incipient movement of salt-free clay mud under salt water conditions (salt water-salt-free clay mud), incipient movement of salt clay mud under salt water conditions (salt water-salt clay mud), and incipient movement of salt clay mud under freshwater conditions (freshwater-salt clay mud), using a circulating flume, in which the salinity of the water body or cohesive sediment varies from 0 to 40%. Based on the particle image velocimetry system and digital image gray processing technology, the gray curves of water near the clay mud bed surface with the velocity were plotted to quantitatively differentiate the incipient velocity of the sediment for each test. The experimental results showed that the higher the salinity of the water body or cohesive sediments is, the more difficult it is to start moving. There is a logarithmic relationship between the incipient velocity of cohesive sediments and the salinity of the water or cohesive sediments. The incipient velocity increases sharply at a salinity of 0â¼10% and slowly at a salinity of 10â¼40%. At the same salinity, the incipient velocity of salt clay mud under freshwater conditions is the largest, followed by that of salt clay mud under salt water conditions, while that of salt-free clay mud under salt water conditions is the smallest. In addition, the flow turbulence characteristics were analyzed under the critical conditions of the onset of muddy clay. Ultimately, an empirical formula to calculate the critical incipient velocity of muddy clay is proposed by introducing the salinity. In this study, salinity is included as a reference variable, which expands the research scope of sediment initiation and provides a reference for the study of estuary dynamics.
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Água Doce , Salinidade , Argila , ÁguaRESUMO
Screening for and identifying patients with Parkinson's disease (PD) at an early stage and forming accurate diagnosis of PD during the course of the progression of the disease are of essential importance but still remain challenging for the clinical diagnosis and treatment of PD. One of the common clinical manifestations of PD is speech impairment, or voice impairment. Thanks to the recent advances in the field of acoustic analysis, a large number of acoustic parameters have been proposed for evaluating speech impairment quantitatively. Early identification and accurate diagnosis of PD was henceforth made possible through the application of speech acoustic analysis. Herein, we summarized the latest research findings on the application of acoustic analysis in PD diagnosis. We reported some acoustic parameters commonly used in the evaluation of voice impairment in PD patients. Then, we presented the diagnostic value of acoustic analysis in developing accurate diagnosis, early screening and differential diagnosis. Furthermore, we discussed the drawbacks and prospects of current studies, intending to enhance understanding of acoustic analysis of PD patients and its potential diagnostic values.