44 research outputs found
An investigation into frequency resolution estimation model for impact signal analysis by using Hilbert spectrum and condition classification for marine diesel engine
In this paper, frequency resolution determination method is investigated according to Hilbert spectrum performance for impact signal analysis. A new constructed performance estimation model for the best frequency resolution is put forward in this research for the impact signal pattern recognition. Different parameters in the time-frequency distribution by using Hilbert spectrum are considered in this estimation model for the best frequency resolution determination. To verify the effectiveness of this estimation model, numerical simulation is used for Hilbert spectrum construction analysis. At the same time, different marine diesel engine working condition signals analysis are also used to illustrate the methodology developed in this research and verify the effectiveness. It can be concluded that this method can contribute the development for impact signal analysis by using Hilbert spectrum
LAMP-2C inhibits MHC class II presentation of cytoplasmic antigens by disrupting chaperone-mediated autophagy
Cells use multiple autophagy pathways to sequester macromolecules, senescent organelles, and pathogens. Several conserved isoforms of the lysosome-associated membrane protein-2 (LAMP-2) regulate these pathways influencing immune recognition and responses. LAMP-2A is required for chaperone-mediated autophagy (CMA), which promotes Ag capture and MHC class II (MHCII) presentation in B cells and signaling in T cells. LAMP-2B regulates lysosome maturation to impact macroautophagy and phagocytosis. Yet, far less is known about LAMP-2C function. Whereas LAMP2A and LAMP2B mRNA were broadly detected in human tissues, LAMP2C expression was more limited. Transcripts for the three LAMP2 isoforms increased with B cell activation, although specific gene induction varied depending on TLR versus BCR engagement. To examine LAMP-2C function in human B cells and specifically its role in Ag presentation, we used ectopic gene expression. Increased LAMP-2C expression in B cells did not alter MHCII expression or invariant chain processing, but did perturb cytoplasmic Ag presentation via CMA. MHCII presentation of epitopes from exogenous and membrane Ags was not affected by LAMP-2C expression in B cells. Similarly, changes in B cell LAMP-2C expression did not impact macroautophagy. The gene expression of other LAMP2 isoforms and proteasome and lysosomal proteases activities were unperturbed by LAMP-2C ectopic expression. LAMP-2C levels modulated the steady-state expression of several cytoplasmic proteins that are targeted for degradation by CMA and diminished peptide translocation via this pathway. Thus, LAMP-2C serves as a natural inhibitor of CMA that can selectively skew MHCII presentation of cytoplasmic Ags
Genomic characterization of pediatric Bâlymphoblastic lymphoma and Bâlymphoblastic leukemia using formalinâfixed tissues
BackgroundRecurrent genomic changes in Bâlymphoblastic leukemia (BâALL) identified by genomeâwide singleânucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, Bâlymphoblastic lymphoma (BâLBL), is limited by the low incidence and lack of fresh tissue for genomic testing.ProcedureWe used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalinâfixed paraffinâembedded pediatric BâLBL (n = 23) and BâALL (n = 55).ResultsSimilar to BâALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26%) BâLBL cases. Eleven of 23 (48%) BâLBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of BâALL. IKZF1 and PAX5 deletions were observed in 13 and 17% of BâLBL, respectively, which was similar to the reported frequency in BâALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22%) BâLBL cases, compared with only 1% in BâALL samples. None of the BâLBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25% of BâALL.ConclusionsOur study demonstrates that the copy number profile of BâLBL is distinct from BâALL, suggesting possible differences in pathogenesis between these closely related diseases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137353/1/pbc26363.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137353/2/pbc26363_am.pd
Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice
© 2019 American Society for Investigative Pathology Single-nucleotide polymorphisms and rare mutations in factor H (FH; official name, CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FH R/R ) share features with human atypical hemolytic uremic syndrome. Herein, we report that FH R/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FH R/R mice. Optical coherence tomography imaging of FH R/R mice showed retinal degeneration, edema, and detachment. Histologic analysis of FH R/R mice revealed retinal thinning, vessel occlusion, as well as degeneration of photoreceptors and retinal pigment epithelium. Immunofluorescence showed albumin leakage from blood vessels into the neural retina, and electron microscopy demonstrated vascular endothelial cell irregularity with narrowing of retinal and choroidal vessels. Knockout of C6, a component of the membrane attack complex, prevented the aforementioned retinal phenotype in FH R/R mice, consistent with membrane attack complexâmediated pathogenesis. Pharmacologic blockade of C5 also rescued retinas of FH R/R mice. This FH R/R mouse strain represents a model for retinal vascular occlusive disorders and ischemic retinopathy. The results suggest complement dysregulation can contribute to retinal vascular occlusion and that an anti-C5 antibody might be helpful for C5-mediated thrombotic retinal diseases
The function of lamp-2 isoforms in MHC class II-restricted cytoplasmic antigen presentation and lysosome biogenesis
This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department ([email protected])
Numerical Study of Damage to Rock Surrounding an Underground Coal Roadway Excavation
In coal mines, underground roadways are required to transport coal and personnel. Such tunnels can become unstable and hazardous. This study simulates deformation and damage in the rock surrounding a shallow coal seam roadway using particle flow code. A numerical model of particle flow in the surrounding rock was constructed based on field survey and drilling data. Microcharacteristic indices, including stress, displacement, and microcrack fields, were used to study deformation and damage characteristics and mechanisms in the surrounding rocks. The results show that the stress within the rock changed gradually from a vertical stress to a circumferential stress pattern. Stress release led to self-stabilizing diamond-shaped and X-shaped tensile stress distribution patterns after the excavation of the roadway. Cracking increased and eventually formed cut-through cracks as the concentrated stress transferred to greater depths at the sides, forming shear and triangular-shaped failure regions. Overall, the roof and floor were relatively stable, whereas the sidewalls gradually failed. These results provide a reference for the control of rock surrounding roadways in coal mines