We present a simple and fast geometric method for modeling data by a union of affine subspaces. The method begins by forming a collection of local best-fit affine subspaces, i.e., subspaces approximating the data in local neighborhoods. The correct sizes of the local neighborhoods are determined automatically by the Jones' β 2 numbers (we prove under certain geometric conditions that our method finds the optimal local neighborhoods). The collection of subspaces is further processed by a greedy selection procedure or a spectral method to generate the final model. We discuss applications to tracking-based motion segmentation and clustering of faces under different illuminating conditions. We give extensive experimental evidence demonstrating the state of the art accuracy and speed of the suggested algorithms on these problems and also on synthetic hybrid linear data as well as the MNIST handwritten digits data; and we demonstrate This work was supported by NSF grants DMS-06-12608, DMS-08-11203, DMS-09-15064 and DMS-09-56072. Thanks to the action editor and the reviewers for the careful reading and comments; Peter Jones, Mauro Maggioni and Amit Singer for discussions that motivated our exploration for a multiscale SVD-based HLM algorithm; Ehsan Elhamifar and René Vidal for answering various questions regarding the SSC code and providing us an initial version before the code was available to the public; Allen Yang for clarifying the estimation of the number of clusters in GPCA; and the IMA for a stimulating multi-manifold modeling workshop.Corresponding Author: Gilad Lerman, how to use our algorithms for fast determination of the number of affine subspaces. Supp. webpage:

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Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through secreting exosomes. The limited numbers of NPCs in adult brain and the decline of NPC pool in many neurological disorders restrain the further use of exosomes in treating these diseases. The direct conversion of somatic cells into induced NPCs (iNPCs) provides abundant NPC-like cells to study the therapeutic effects of NPCs-originated exosomes (EXOs). Our recent study demonstrated that iNPCs-derived exosomes (iEXOs) exhibit distinct potential in facilitating the proliferation of NPCs, compared to EXOs, indicating the importance to investigate the effects of EXOs and iEXOs on the differentiation of NPCs, which remains unknown. Here, our results suggest that EXOs, but not iEXOs, promoted neuronal differentiation and neither of them had effect on glial generation. Microarray analysis revealed different miRNA signatures in EXOs and iEXOs, in which miR-21a was highly enriched in EXOs. Perturbation of function assay demonstrated the key roles of miR-21a in the generation of neurons and mediating the neurogenic potential of exosomes. Our data suggest that EXOs and iEXOs may achieve their therapeutic effects in promoting neurogenesis through transferring key miRNAs, which sheds light on the development of highly efficient cell-free therapeutic strategies for treating neurological diseases. Electronic supplementary material The online version of this article (10.1186/s12964-019-0418-3) contains supplementary material, which is available to authorized users.

Time-resolved imaging is crucial for the accurate diagnosis of liver lesions. Current contrast enhanced liver magnetic resonance imaging acquires a few phases in sequential breath-holds. The image quality is susceptible to bolus timing errors, which could result in missing the critical arterial phase. This impairs the detection of malignant tumors that are supplied primarily by the hepatic artery. In addition, the temporal resolution may be too low to reliably separate the arterial phase from the portal venous phase. In this study, a method called temporal resolution acceleration with constrained evolution reconstruction was developed with three-dimensional volume coverage and high-temporal frame rate. Data is acquired using a stack of spirals sampling trajectory combined with a golden ratio view order using an eight-channel coil array. Temporal frames are reconstructed from vastly undersampled data sets using a nonlinear inverse algorithm assuming that the temporal changes are small at short time intervals. Numerical and phantom experimental validation is presented. Preliminary in vivo results demonstrated high spatial resolution dynamic three-dimensional images of the whole liver with high frame rates, from which numerous subarterial phases could be easily identified retrospectively.

Microglial activation is a key pathogenic process at the onset of Alzheimer’s disease (AD). Identifying regulators of microglial activation bears great potential in elucidating causes and mechanisms of AD and determining candidates for early intervention. Previous studies demonstrate abnormal elevation of glutaminase C (GAC) in HIV-infected or immune-activated microglia. However, whether GAC elevation causes microglial activation remains unknown. In this study, we found heightened expression levels of GAC in early AD mouse brain tissues compared with those in control littermates. Investigations on an in vitro neuroinflammation model revealed that GAC is increased in primary mouse microglia following pro-inflammatory stimulation. To model GAC elevation we overexpressed GAC by plasmid transfection and observed that GAC-overexpression shift the microglial phenotype to a pro-inflammatory state. Treatment with BPTES, a glutaminase inhibitor, reversed LPS-induced microglial activation and inflammation. Furthermore, we discovered that GAC overexpression in mouse microglia increased exosome release and changed exosome content, which includes specific packaging of pro-inflammatory miRNAs that activate microglia. Together, our results demonstrate a causal effect of GAC elevation on microglial activation and exosome release, both of which promote the establishment of a pro-inflammatory microenvironment. Therefore, GAC may have important relevance to the pathogenesis of AD.

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We aimed to summarize reliable medical evidence by the meta-analysis of all published clinical trials that investigated the safety, tolerability, and immunogenicity of vaccine candidates against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The PubMed, Cochrane Library, EMBASE, and medRxiv databases were used to select the studies. 7094 articles were identified initially and 43 were retrieved for more detailed evaluation. 5 randomized, double-blind, placebo-controlled trials were selected. A total of 1604 subjects with either vaccines or placebo infections were included in the meta-analysis within the scope of these articles. According to the results, there is an increase in total adverse events for subjects with either low (95% CI: 1.90-4.29) or high (CI: 2.65-5.63) dose vaccination. The adverse effects of COVID-19 vaccine are mainly local ones including pain, itching, and redness, and no significant difference was identified in the systemic reactions. All adverse effects were transient and resolved within a few days. Moreover, the neutralizing and IgG antibody levels post different dose vaccinations were all significantly increased at day 14/21 (P = 0.0004 and P = 0.0003, respectively) and day 28/35 (P < 0.00001) in vaccine groups compared to placebo controls. Besides, the levels of neutralizing and IgG antibodies were also elevated significantly at from day 14 to 35, versus day 0 (All P < 0.001). In conclusion, our analysis suggests that the current COVID-19 vaccine candidates are safe, tolerated, and immunogenic, which provides important information for further development, evaluation, and clinical application of COVID-19 vaccine.