Language Model Combination and Adaptation Using Weighted Finite State Transducers

In speech recognition systems language model (LMs) are often constructed by training and combining multiple n-gram models. They can be either used to represent different genres or tasks found in diverse text sources, or capture stochastic properties of different linguistic symbol sequences, for example, syllables and words. Unsupervised LM adaption may also be used to further improve robustness to varying styles or tasks. When using these techniques, extensive software changes are often required. In this paper an alternative and more general approach based on weighted finite state transducers (WFSTs) is investigated for LM combination and adaptation. As it is entirely based on well-defined WFST operations, minimum change to decoding tools is needed. A wide range of LM combination configurations can be flexibly supported. An efficient on-the-fly WFST decoding algorithm is also proposed. Significant error rate gains of 7.3% relative were obtained on a state-of-the-art broadcast audio recognition task using a history dependently adapted multi-level LM modelling both syllable and word sequence

Speaker diarisation and longitudinal linking in multi-genre broadcast data

This paper presents a multi-stage speaker diarisation system with longitudinal linking developed on BBC multi-genre data for the 2015 Multi-Genre Broadcast (MGB) challenge. The basic speaker diarisation system draws on techniques from the Cambridge March 2005 system with a new deep neural network (DNN)-based speech/non speech segmenter. A newly developed linking stage is next added to the basic diarisation output aiming at the identification of speakers across multiple episodes of the same series. The longitudinal constraint imposes an incremental processing of the episodes, where speaker labels for each episode can be obtained using only material from the episode in question, and those broadcast earlier in time. The nature of the data as well as the longitudinal linking constraint position this diarisation task as a new open-research topic, and a particularly challenging one. Different linking clustering metrics are compared and the lowest within-episode and cross-episode DER scores are achieved on the MGB challenge evaluation set.This work is in part supported by EPSRC Programme Grant EP/I031022/1 (Natural Speech Technology). C. Zhang is also supported by a Cambridge International Scholarship from the Cambridge Commonwealth, European & International Trust.This is the author accepted manuscript. The final version is available from IEEE via http://dx.doi.org/10.1109/ASRU.2015.740485

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

Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance

Despite improved outcomes in multiple myeloma (MM), a cure remains elusive. However, even before the current therapeutic era, 5% of patients survived >10 years and we propose that immune factors contribute to this longer survival. We identified patient

Relating Dynamic Brain States to Dynamic Machine States: Human and Machine Solutions to the Speech Recognition Problem

There is widespread interest in the relationship between the neurobiological systems supporting human cognition and emerging computational systems capable of emulating these capacities. Human speech comprehension, poorly understood as a neurobiological process, is an important case in point. Automatic Speech Recognition (ASR) systems with near-human levels of performance are now available, which provide a computationally explicit solution for the recognition of words in continuous speech. This research aims to bridge the gap between speech recognition processes in humans and machines, using novel multivariate techniques to compare incremental ‘machine states’, generated as the ASR analysis progresses over time, to the incremen- tal ‘brain states’, measured using combined electro- and magneto-encephalography (EMEG), generated as the same inputs are heard by human listeners. This direct comparison of dynamic human and machine internal states, as they respond to the same incrementally delivered sensory input, revealed a significant correspondence between neural response patterns in human superior temporal cortex and the structural properties of ASR-derived phonetic models. Spatially coherent patches in human temporal cortex responded selectively to individual phonetic features defined on the basis of machine-extracted regularities in the speech to lexicon mapping process. These results demonstrate the feasibility of relating human and ASR solutions to the problem of speech recognition, and suggest the potential for further studies relating complex neural computations in human speech comprehension to the rapidly evolving ASR systems that address the same problem domain.This research was supported financially by an Advanced Investigator grant to WMW from the European Research Council (AdG 230570 NEUROLEX), by MRC Cognition and Brain Sciences Unit (CBSU) funding to WMW (U.1055.04.002.00001.01), and by a European Research Council Advanced Investigator grant under the European Community’s Horizon 2020 Research and Innovation Programme (2014-2020 ERC Grant agreement no 669820) to Lorraine K. Tyler. LS was partly supported by the NIHR Biomedical Research Centre and Biomedical Unit in Dementia based at Cambridge University Hospital NHS Foundation Trust

De-Industrialisation, Entrepreneurial Industries and Welfare

We develop a two-sector general equilibrium model with monopolistic competition featuring nonhomothetic production and a variable demand elasticity for the manufactured goods. An increase in the relative price of manufacturing varieties can lead to a decline in total industrial output in our framework, i.e., to de-industrialisation. The two key mechanisms behind this surprising result are that the founding of firms requires skilled labour as a fixed input requirement, and that the price increase can raise the profit margin in the manufacturing industry and thereby induce firm entry. When the manufacturing sector mainly adjusts at the extensive margin, we refer to this industry as being entrepreneurial. Due to the fixed input requirement entry reduces the effective endowment of skilled labour available for production. This reduces industrial output owing to a novel generalized version of the Rybczynski effect. De-industrialisation occurs if that effect is sufficiently large in comparison with the standard output price effect for a given number of firms. Furthermore we prove the counterintuitive result that de-industrialisation implies a fall in the output per firm and under plausible conditions a rise in welfare. Our results shed new light on the current debates about possible causes of premature de-industrialisation and its welfare effects

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles