Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.

Retinal degeneration often results in the loss of light-sensing photoreceptors, which leads to permanent vision loss. Generating transplantable retinal photoreceptors using human somatic cell-derived induced pluripotent stem cells (iPSCs) holds promise to treat a variety of retinal degenerative diseases by replacing the damaged or dysfunctional native photoreceptors with healthy and functional ones. Establishment of effective methods to produce retinal cells including photoreceptors in chemically defined conditions using current Good Manufacturing Practice (cGMP)-manufactured human iPSC lines is critical for advancing cell replacement therapy to the clinic. In this study, we used a human iPSC line (NCL-1) derived under cGMP-compliant conditions from CD34+ cord blood cells. The cells were differentiated into retinal cells using a small molecule-based retinal induction protocol. We show that retinal cells including photoreceptors, retinal pigmented epithelial cells and optic cup-like retinal organoids can be generated from the NCL-1 iPSC line. Additionally, we show that following subretinal transplantation into immunodeficient host mouse eyes, retinal cells successfully integrated into the photoreceptor layer and developed into mature photoreceptors. This study provides strong evidence that transplantable photoreceptors can be generated from a cGMP-manufactured human iPSC line for clinical applications. Stem Cells Translational Medicine 2018;7:210-219

Distributed formation tracking using local coordinate systems

This paper studies the formation tracking problem for multi-agent systems, for which a distributed estimator–controller scheme is designed relying only on the agents’ local coordinate systems such that the centroid of the controlled formation tracks a given trajectory. By introducing a gradient descent term into the estimator, the explicit knowledge of the bound of the agents’ speed is not necessary in contrast to existing works, and each agent is able to compute the centroid of the whole formation in finite time. Then, based on the centroid estimation, a distributed control algorithm is proposed to render the formation tracking and stabilization errors to converge to zero, respectively. Finally, numerical simulations are carried to validate our proposed framework for solving the formation tracking problem

Constraints on Lema\^{\i}tre-Tolman-Bondi models from Observational Hubble Parameter data

We use the observational Hubble parameter data (OHD), both the latest observational dataset (Stern et al. 2010, referred to as SJVKS) and the simulated datasets, to constrain Lema\^{\i}tre-Tolman-Bondi (LTB) void models. The necessity of the consistency check on OHD itself in the LTB cosmology is stressed. Three voids are chosen as test models and are constrained using the Union2 dataset of SN Ia as well as OHD. Despite their different parametrization, the results from our test models show some indicating similarities, e.g., the best-fit voids obtained from OHD are all considerably broader than those from SN Ia. Due to the small size of the SJVKS dataset, the constraints are not conclusive. The constraining power of the future OHD observations are therefore investigated, through a Figure of Merit (FoM) analysis based on the Monte Carlo simulated data. We found that, in the case that the future OHD become more consistent with SN Ia, the results from the test models are almost unanimous: 1) as many as 32 OHD data points at the SJVKS-like uncertainty level are needed to give a higher FoM than the Union2 dataset of SN Ia; 2) precise observation helps reduce this required number; 3) increasing the survey depth does not always increase the FoM. On the other hand, if the future OHD and the Union2 dataset keep favor different voids, in a similar manner as they do at present, the 1{\sigma} confidence regions obtained from the two probes should finally separate. We test this conjecture and found that, the minimum observational requirement (the size of the dataset, the uncertainty level and the survey depth) for this inconsistency to emerge depends strongly on the void model.Comment: 14 pages, 14 figures, 5 tables, accepted for publication in Ap

Epstein-Barr Virus BART9 miRNA Modulates LMP1 Levels and Affects Growth Rate of Nasal NK T Cell Lymphomas

Nasal NK/T cell lymphomas (NKTCL) are a subset of aggressive Epstein-Barr virus (EBV)-associated non-Hodgkin's lymphomas. The role of EBV in pathogenesis of NKTCL is not clear. Intriguingly, EBV encodes more than 40 microRNAs (miRNA) that are differentially expressed and largely conserved in lymphocryptoviruses. While miRNAs play a critical role in the pathogenesis of cancer, especially lymphomas, the expression and function of EBV transcribed miRNAs in NKTCL are not known. To examine the role of EBV miRNAs in NKTCL, we used microarray profiling and qRT-PCR to identify and validate expression of viral miRNAs in SNK6 and SNT16 cells, which are two independently derived NKTCL cell lines that maintain the type II EBV latency program. All EBV BART miRNAs except BHRF-derived miRNAs were expressed and some of these miRNAs are expressed at higher levels than in nasopharyngeal carcinomas. Modulating the expression of BART9 with antisense RNAs consistently reduced SNK6 and SNT16 proliferation, while antisense RNAs to BARTs-7 and -17-5p affected proliferation only in SNK6 cells. Furthermore, the EBV LMP-1 oncoprotein and transcript levels were repressed when an inhibitor of BART9 miRNA was transfected into SNK6 cells, and overexpression of BART9 miRNA increased LMP-1 protein and mRNA expression. Our data indicate that BART9 is involved in NKTCL proliferation, and one of its mechanisms of action appears to be regulating LMP-1 levels. Our findings may have direct application for improving NKTCL diagnosis and for developing possible novel treatment approaches for this tumor, for which current chemotherapeutic drugs have limited effectiveness

The function of FGF signaling in the lens placode

AbstractPrevious studies suggested that FGF signaling is important for lens formation. However, the times at which FGFs act to promote lens formation, the FGFs that are involved, the cells that secrete them and the mechanisms by which FGF signaling may promote lens formation are not known. We found that transcripts encoding several FGF ligands and the four classical FGF receptors are detectable in the lens-forming ectoderm at the time of lens induction. Conditional deletion of Fgfr1 and Fgfr2 from this tissue resulted in the formation of small lens rudiments that soon degenerated. Lens placodes lacking Fgfr1 and 2 were thinner than in wild-type embryos. Deletion of Fgfr2 increased cell death from the initiation of placode formation and concurrent deletion of Fgfr1 enhanced this phenotype. Fgfr1/2 conditional knockout placode cells expressed lower levels of proteins known to be regulated by FGF receptor signaling, but proteins known to be important for lens formation were present at normal levels in the remaining placode cells, including the transcription factors Pax6, Sox2 and FoxE3 and the lens-preferred protein αA-crystallin. Previous studies identified a genetic interaction between BMP and FGF signaling in lens formation and conditional deletion of Bmpr1a caused increased cell death in the lens placode, resulting in the formation of smaller lenses. In the present study, conditional deletion of both Bmpr1a and Fgfr2 increased cell death beyond that seen in Fgfr2CKO placodes and prevented lens formation. These results suggest that the primary role of autocrine or paracrine FGF signaling is to provide essential survival signals to lens placode cells. Because apoptosis was already increased at the onset of placode formation in Fgfr1/2 conditional knockout placode cells, FGF signaling was functionally absent during the period of lens induction by the optic vesicle. Since the expression of proteins required for lens formation was not altered in the knockout placode cells, we can conclude that FGF signaling from the optic vesicle is not required for lens induction

Designing an object-based preproduction tool for multiscreen TV viewing

Multiscreen TV viewing refers to a spectrum of media productions that can be watched using TV and companion screens such as smartphones and tablets. In the last several years, companies are creating companion applications to enrich the TV viewing experience

Predicting visual context for unsupervised event segmentation in continuous photo-streams

Segmenting video content into events provides semantic structures for indexing, retrieval, and summarization. Since motion cues are not available in continuous photo-streams, and annotations in lifelogging are scarce and costly, the frames are usually clustered into events by comparing the visual features between them in an unsupervised way. However, such methodologies are ineffective to deal with heterogeneous events, e.g. taking a walk, and temporary changes in the sight direction, e.g. at a meeting. To address these limitations, we propose Contextual Event Segmentation (CES), a novel segmentation paradigm that uses an LSTM-based generative network to model the photo-stream sequences, predict their visual context, and track their evolution. CES decides whether a frame is an event boundary by comparing the visual context generated from the frames in the past, to the visual context predicted from the future. We implemented CES on a new and massive lifelogging dataset consisting of more than 1.5 million images spanning over 1,723 days. Experiments on the popular EDUB-Seg dataset show that our model outperforms the state-of-the-art by over 16% in f-measure. Furthermore, CES' performance is only 3 points below that of human annotators.Comment: Accepted for publication at the 2018 ACM Multimedia Conference (MM '18