The 2016 KIT IWSLT Speech-to-Text Systems for English and German

This paper describes our German and English Speech-to-Text (STT) systems for the 2016 IWSLT evaluation campaign. The campaign focuses on the transcription of unsegmented TED talks. Our setup includes systems using both the Janus and Kaldi frameworks. We combined the outputs using both ROVER [1] and confusion network combination (CNC) [2] to archieve a good overall performance. The individual subsystems are built by using different speaker-adaptive feature combination (e.g., lMEL with i-vector or bottleneck speaker vector), acoustic models (GMM or DNN) and speaker adaption (MLLR or fMLLR). Decoding is performed in two stages, where the GMM and DNN systems are adapted on the combination of the first stage outputs using MLLR, and fMLLR. The combination setup produces a final hypothesis that has a significantly lower WER than any of the individual subsystems. For the English TED task, our best combination system has a WER of 7.8% on the development set while our other combinations gained 21.8% and 28.7% WERs for the English and German MSLT tasks

Corneal Limbal Microenvironment Can Induce Transdifferentiation of Hair Follicle Stem Cells into Corneal Epithelial-like Cells

The aim of this study was to investigate the transdifferentiation potential of murine vibrissa hair follicle (HF) stem cells into corneal epithelial-like cells through modulation by corneal- or limbus-specific microenvironmental factors. Adult epithelial stem cells were isolated from the HF bulge region by mechanical dissection or fluorescence-activated cell sorting using antibodies to α6 integrin, enriched by clonal expansion, and subcultivated on various extracellular matrices (type IV collagen, laminin-1, laminin-5, fibronectin) and in different conditioned media derived from central and peripheral corneal fibroblasts, limbal stromal fibroblasts, and 3T3 fibroblasts. Cellular phenotype and differentiation were evaluated by light and electron microscopy, real-time reverse transcription-polymerase chain reaction, immunocytochemistry, and Western blotting, using antibodies against putative stem cell markers (K15, α6 integrin) and differentiation markers characteristic for corneal epithelium (K12, Pax6) or epidermis (K10). Using laminin-5, a major component of the corneo-limbal basement membrane zone, and conditioned medium from limbal stromal fibroblasts, clonally enriched HF stem and progenitor cells adhered rapidly and formed regularly arranged stratified cell sheets. Conditioned medium derived from limbal fibroblasts markedly upregulated expression of cornea-specific K12 and Pax6 on the mRNA and protein level, whereas expression of the epidermal keratinocyte marker K10 was strongly downregulated. These findings suggest that adult HF epithelial stem cells are capable of differentiating into corneal epithelial-like cells in vitro when exposed to a limbus-specific microenvironment. Therefore, the HF may be an easily accessible alternative therapeutic source of autologous adult stem cells for replacement of the corneal epithelium and restoration of visual function in patients with ocular surface disorders

Common genetic determinants of intraocular pressure and primary open-angle Glaucoma

10.1371/journal.pgen.1002611PLoS Genetics85

Schlötzer-Schrehardt U. Impaired cytoprotective mechanisms in eyes with pseudoexfoliation syndrome/glaucoma. Invest Ophthalmol Vis Sci 2007

PURPOSE. Evidence suggests that chronically increased stress conditions in the anterior eye segment constitute major mechanisms involved in the pathobiology of pseudoexfoliation (PEX) syndrome. The expression of stress-related genes in eyes from patients with and without PEX syndrome/glaucoma was investigated to determine whether PEX syndrome is associated with an altered cellular stress response. METHODS. cDNA array hybridization, quantitative real-time PCR, Western blot analysis, and immunohistochemistry were applied to analyze the mRNA and protein expression of stressrelated genes in anterior segment tissues of PEX eyes, with and without glaucoma, and to compare them with normal and glaucomatous control eyes. RESULTS. Hybridization of cDNA arrays identified a set of stressrelated candidate genes for differential expression in PEX syndrome/glaucoma, of which 10 were confirmed by real-time PCR in ciliary processes and iris tissue. The expression of MAPKp38, heat shock proteins (HSP40, HSP60), and superoxide dismutase (SOD2) was increased up to threefold in PEX specimens. In contrast, a large set of cytoprotective gene products, including antioxidant defense enzymes (glutathione S-transferases mGST1 and GSTT1), ubiquitin-conjugating enzymes (UBE2A, UBE2B), the DNA repair protein MLH1, and the stress-inducible transcription factor GADD153, were found to be consistently downregulated up to threefold in PEX specimens on both the mRNA and protein levels. CONCLUSIONS. The present findings provide evidence of alterations in cytoprotective mechanisms including antioxidant defense, proteasome function, endoplasmic reticulum-related stress response, and DNA repair in anterior segment tissues of PEX eyes. The resultant enhanced sensitivity and vulnerability to cellular stress conditions may therefore be one contributing factor in the pathobiology of PEX syndrome. (Invest Ophthalmol Vis Sci. 2007;48:5558 -5566) DOI:10.1167/iovs.07-0750 P seudoexfoliation (PEX) syndrome is a generalized disorder of the extracellular matrix and currently represents the most commonly identified specific cause of open-angle glaucoma. 1 The pathologic process is characterized by the chronic, stable accumulation of abnormal fibrillar aggregates in the anterior segment and various extraocular tissues. 2 Recent molecular biological evidence suggests that PEX syndrome is an elastic microfibrillopathy associated with an excessive production of elastic microfibril components, such as fibrillin-1 and latent transforming growth factor-binding proteins, enzymatic cross-linking processes, increased levels of transforming growth factor (TGF)-␤1, and a proteolytic imbalance between matrix metalloproteinases and their inhibitors. 3,4 A recent proteomic approach confirmed the presence of elastic fiber components within PEX deposits and provided evidence of further constituents, such as fibulin-2, syndecan-3, versican, metalloproteases of the ADAM family, and complement factor C1q. There is increasing evidence that cellular stress conditions, such as anterior chamber ischemia/hypoxia and oxidative stress, may constitute major mechanisms involved in the pathobiology of PEX syndrome, and several studies suggest impaired antioxidative protection mechanisms in patients with PEX. 6 -8 Increased endothelin-1 and homocysteine levels in the aqueous humor of PEX eyes may further contribute to ischemic alterations and oxidative stress. 11 In addition, the activity of superoxide dismutase was significantly decreased, and products of protein oxidation were significantly increased in serum samples of patients with PEX compared with control patients. 12 All mammalian cells possess an innate strategy for preventing stress-induced injury or cell death and for recovering from acute or chronic stress conditions by activating a host of cytoprotective mechanisms. Even in the presence of existing stress conditions in the anterior segment, previous studies showed a significant downregulation of protective genes, such as clusterin, a small heat shock protein-like chaperone, in anterior segment tissues of PEX eyes, indicating impaired cellular protection mechanisms

Identification, Isolation, and Characterization of Melanocyte Precursor Cells in the Human Limbal Stroma

Given their vital role in the homeostasis of the limbal stem cell niche, limbal melanocytes have emerged as promising candidates for tissue engineering applications. This study aimed to isolate and characterize a population of melanocyte precursors in the limbal stroma, compared with melanocytes originating from the limbal epithelium, using magnetic-activated cell sorting (MACS) with positive (CD117/c-Kit microbeads) or negative (CD326/EpCAM or anti-fibroblast microbeads) selection approaches. Both approaches enabled fast and easy isolation and cultivation of pure limbal epithelial and stromal melanocyte populations, which differed in phenotype and gene expression, but exhibited similar functional properties regarding proliferative potential, pigmentation, and support of clonal growth of limbal epithelial stem/progenitor cells (LEPCs). In both melanocyte populations, limbus-specific matrix (laminin 511-E8) and soluble factors (LEPC-derived conditioned medium) stimulated melanocyte adhesion, dendrite formation, melanogenesis, and expression of genes involved in UV protection and immune regulation. The findings provided not only a novel protocol for the enrichment of pure melanocyte populations from limbal tissue applying easy-to-use MACS technology, but also identified a population of stromal melanocyte precursors, which may serve as a reservoir for the replacement of damaged epithelial melanocytes and an alternative resource for tissue engineering applications

Identification, Isolation, and Characterization of Melanocyte Precursor Cells in the Human Limbal Stroma

Given their vital role in the homeostasis of the limbal stem cell niche, limbal melanocytes have emerged as promising candidates for tissue engineering applications. This study aimed to isolate and characterize a population of melanocyte precursors in the limbal stroma, compared with melanocytes originating from the limbal epithelium, using magnetic-activated cell sorting (MACS) with positive (CD117/c-Kit microbeads) or negative (CD326/EpCAM or anti-fibroblast microbeads) selection approaches. Both approaches enabled fast and easy isolation and cultivation of pure limbal epithelial and stromal melanocyte populations, which differed in phenotype and gene expression, but exhibited similar functional properties regarding proliferative potential, pigmentation, and support of clonal growth of limbal epithelial stem/progenitor cells (LEPCs). In both melanocyte populations, limbus-specific matrix (laminin 511-E8) and soluble factors (LEPC-derived conditioned medium) stimulated melanocyte adhesion, dendrite formation, melanogenesis, and expression of genes involved in UV protection and immune regulation. The findings provided not only a novel protocol for the enrichment of pure melanocyte populations from limbal tissue applying easy-to-use MACS technology, but also identified a population of stromal melanocyte precursors, which may serve as a reservoir for the replacement of damaged epithelial melanocytes and an alternative resource for tissue engineering applications