The intrinsic stiffness of human trabecular meshwork cells increases with senescence.

Dysfunction of the human trabecular meshwork (HTM) plays a central role in the age-associated disease glaucoma, a leading cause of irreversible blindness. The etiology remains poorly understood but cellular senescence, increased stiffness of the tissue, and the expression of Wnt antagonists such as secreted frizzled related protein-1 (SFRP1) have been implicated. However, it is not known if senescence is causally linked to either stiffness or SFRP1 expression. In this study, we utilized in vitro HTM senescence to determine the effect on cellular stiffening and SFRP1 expression. Stiffness of cultured cells was measured using atomic force microscopy and the morphology of the cytoskeleton was determined using immunofluorescent analysis. SFRP1 expression was measured using qPCR and immunofluorescent analysis. Senescent cell stiffness increased 1.88±0.14 or 2.57±0.14 fold in the presence or absence of serum, respectively. This was accompanied by increased vimentin expression, stress fiber formation, and SFRP1 expression. In aggregate, these data demonstrate that senescence may be a causal factor in HTM stiffening and elevated SFRP1 expression, and contribute towards disease progression. These findings provide insight into the etiology of glaucoma and, more broadly, suggest a causal link between senescence and altered tissue biomechanics in aging-associated diseases

Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

Background/objectivesThe common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.MethodsFor immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.ResultsHomozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.ConclusionsIn sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression

Model-corrected microwave imaging through periodic wall structures

A model-based imaging framework is applied to correct the target distortion seen in microwave imaging through a periodic wall structure. In addition to propagation delays caused by the wall, it is shown that the structural periodicity induces high-order space harmonics leading to other ghost artifacts in the through-wall image. To overcome these distortions, the periodic layer Greens function is incorporated into the forward model. A linear back-projection solution and a nonlinear minimization solution are applied to solve the inverse problem. The model-based back-projection image corrects the distortion and has higher resolution compared with free space due to the inclusion of multipath propagation through the periodic wall, but considerable sidelobe clutter is present. The nonlinear solution not only corrects target distortion without clutter but also reduces the solution to a sparse form. © Copyright 2012 Paul C. Chang et al

A conformally invariant sphere theorem in four dimensions

In this paper we provide a sharp characterization of the smooth four-dimensional sphere. The assumptions of the theorem are conformally invariant, and can be reduced to an L^2 inequality of the Weyl tensor and positivity of the Yamabe invariant.Comment: 39 pages, 0 figure

A Projection-Based K-space Transformer Network for Undersampled Radial MRI Reconstruction with Limited Training Subjects

The recent development of deep learning combined with compressed sensing enables fast reconstruction of undersampled MR images and has achieved state-of-the-art performance for Cartesian k-space trajectories. However, non-Cartesian trajectories such as the radial trajectory need to be transformed onto a Cartesian grid in each iteration of the network training, slowing down the training process and posing inconvenience and delay during training. Multiple iterations of nonuniform Fourier transform in the networks offset the deep learning advantage of fast inference. Current approaches typically either work on image-to-image networks or grid the non-Cartesian trajectories before the network training to avoid the repeated gridding process. However, the image-to-image networks cannot ensure the k-space data consistency in the reconstructed images and the pre-processing of non-Cartesian k-space leads to gridding errors which cannot be compensated by the network training. Inspired by the Transformer network to handle long-range dependencies in sequence transduction tasks, we propose to rearrange the radial spokes to sequential data based on the chronological order of acquisition and use the Transformer to predict unacquired radial spokes from acquired ones. We propose novel data augmentation methods to generate a large amount of training data from a limited number of subjects. The network can be generated to different anatomical structures. Experimental results show superior performance of the proposed framework compared to state-of-the-art deep neural networks.Comment: Accepted at MICCAI 202

Overcoming data scarcity of Twitter: using tweets as bootstrap with application to autism-related topic content analysis

Notwithstanding recent work which has demonstrated the potential of using Twitter messages for content-specific data mining and analysis, the depth of such analysis is inherently limited by the scarcity of data imposed by the 140 character tweet limit. In this paper we describe a novel approach for targeted knowledge exploration which uses tweet content analysis as a preliminary step. This step is used to bootstrap more sophisticated data collection from directly related but much richer content sources. In particular we demonstrate that valuable information can be collected by following URLs included in tweets. We automatically extract content from the corresponding web pages and treating each web page as a document linked to the original tweet show how a temporal topic model based on a hierarchical Dirichlet process can be used to track the evolution of a complex topic structure of a Twitter community. Using autism-related tweets we demonstrate that our method is capable of capturing a much more meaningful picture of information exchange than user-chosen hashtags.Comment: IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining, 201

FGF signaling regulates Wnt ligand expression to control vulval cell lineage polarity in C. elegans

The interpretation of extracellular cues leading to the polarization of intracellular components and asymmetric cell divisions is a fundamental part of metazoan organogenesis. The Caenorhabditis elegans vulva, with its invariant cell lineage and interaction of multiple cell signaling pathways, provides an excellent model for the study of cell polarity within an organized epithelial tissue. Here, we show that the fibroblast growth factor (FGF) pathway acts in concert with the Frizzled homolog LIN-17 to influence the localization of SYS-1, a component of the Wnt/β-catenin asymmetry pathway, indirectly through the regulation of cwn-1. The source of the FGF ligand is the primary vulval precursor cell (VPC) P6.p, which controls the orientation of the neighboring secondary VPC P7.p by signaling through the sex myoblasts (SMs), activating the FGF pathway. The Wnt CWN-1 is expressed in the posterior body wall muscle of the worm as well as in the SMs, making it the only Wnt expressed on the posterior and anterior sides of P7.p at the time of the polarity decision. Both sources of cwn-1 act instructively to influence P7.p polarity in the direction of the highest Wnt signal. Using single molecule fluorescence in situ hybridization, we show that the FGF pathway regulates the expression of cwn-1 in the SMs. These results demonstrate an interaction between FGF and Wnt in C. elegans development and vulval cell lineage polarity, and highlight the promiscuous nature of Wnts and the importance of Wnt gradient directionality within C. elegans