Automatic transcription of multi-genre media archives

This paper describes some recent results of our collaborative work on developing a speech recognition system for the automatic transcription or media archives from the British Broadcasting Corporation (BBC). The material includes a wide diversity of shows with their associated metadata. The latter are highly diverse in terms of completeness, reliability and accuracy. First, we investigate how to improve lightly supervised acoustic training, when timestamp information is inaccurate and when speech deviates significantly from the transcription, and how to perform evaluations when no reference transcripts are available. An automatic timestamp correction method as well as a word and segment level combination approaches between the lightly supervised transcripts and the original programme scripts are presented which yield improved metadata. Experimental results show that systems trained using the improved metadata consistently outperform those trained with only the original lightly supervised decoding hypotheses. Secondly, we show that the recognition task may benefit from systems trained on a combination of in-domain and out-of-domain data. Working with tandem HMMs, we describe Multi-level Adaptive Networks, a novel technique for incorporating information from out-of domain posterior features using deep neural network. We show that it provides a substantial reduction in WER over other systems including a PLP-based baseline, in-domain tandem features, and the best out-of-domain tandem features.This research was supported by EPSRC Programme Grant EP/I031022/1 (Natural Speech Technology).This paper was presented at the First Workshop on Speech, Language and Audio in Multimedia, August 22-23, 2013; Marseille. It was published in CEUR Workshop Proceedings at http://ceur-ws.org/Vol-1012/

Multiple myeloma causes clonal T-cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade

© 2016 Macmillan Publishers Limited. Tumour-induced dysfunction of cytotoxic T cells in patients with multiple myeloma (MM) may contribute to immune escape and be responsible for the lack of therapeutic efficacy of immune checkpoint blockade. We therefore investigated dysfunctional clonal T cells in MM and demonstrated immunosenescence but not exhaustion as a predominant feature. T-cell clones were detected in 75% of MM patients and their prognostic significance was revalidated in a new post-immunomodulatory drug cohort. The cells exhibited a senescent secretory effector phenotype: KLRG-1+/CD57+/CD160+/CD28-. Normal-for-age telomere lengths indicate that senescence is telomere independent and potentially reversible. p38-mitogen-activated protein kinase, p16 and p21 signalling pathways known to induce senescence were not elevated. Telomerase activity was found to be elevated and this may explain how normal telomere lengths are maintained in senescent cells. T-cell receptor signalling checkpoints were normal but elevated SMAD levels associated with T-cell inactivation were detected and may provide a potential target for the reversal of clonal T-cell dysfunction in MM. Low programmed death 1 and cytotoxic T-lymphocyte-associated antigen 4 expression detected on T-cell clones infers that these cells are not exhausted but suggests that there would be a suboptimal response to immune checkpoint blockade in MM. Our data suggest that other immunostimulatory strategies are required in MM

Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer

<p>Abstract</p> <p>Background</p> <p>The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer.</p> <p>Methods</p> <p>Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed.</p> <p>Results</p> <p>The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates.</p> <p>Conclusions</p> <p>This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response.</p