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

Spreading of Latex Particles on a Substrate

We have investigated both experimentally and theoretically the spreading behavior of latex particles deposited on solid substrates. These particles, which are composed of cross-linked polymer chains, have an intrinsic elastic modulus. We show that the elasticity must be considered to account for the observed contact angle between the particle and the solid substrate, as measured through atomic force microscopy techniques. In particular, the work of adhesion computed within our model can be significantly larger than that from the classical Dupr\'{e} formula.Comment: 7 pages, 7 figures, to appear in Europhys. Let

Control of Gammaherpesvirus Latency by Latent Antigen-Specific Cd8+ T Cells

The contribution of the latent antigen-specific CD8+ T cell response to the control of gammaherpesvirus latency is currently obscure. Some latent antigens induce potent T cell responses, but little is known about their induction or the role they play during the establishment of latency. Here we used the murine gammaherpesvirus system to examine the expression of the latency-associated M2 gene during latency and the induction of the CD8+ T cell response to this protein. M2, in contrast to the M3 latency-associated antigen, was expressed at day 14 after infection but was undetectable during long-term latency. The induction of the M291–99/Kd CD8+ T cell response was B cell dependent, transient, and apparently induced by the rapid increase in latently infected cells around day 14 after intranasal infection. These kinetics were consistent with a role in controlling the initial “burst” of latently infected cells. In support of this hypothesis, adoptive transfer of an M2-specific CD8+ T cell line reduced the initial load of latently infected cells, although not the long-term load. These data represent the first description of a latent antigen-specific immune response in this model, and suggest that vaccination with latent antigens such as M2 may be capable of modulating latent gammaherpesvirus infection

Effect of Sitting Posture on Development of Scoliosis in Duchenne Muscular Dystrophy Cases

Background: Scoliosis is a frequent association in boys with Duchenne Muscular Dystrophy when the ability to walk is lost around nine to 12 years of age. This study assessed the contribution of physical factors including lumbar posture to scoliosis in non-ambulatory youth with DMD in Nepal. Methods: Linear regression was used to assess effects of time since loss of ambulation, muscle strength, functional severity and lumbar angle as a binary variable on coronal Cobb angle; again logistic regression was used to assess effects of muscle strength and cross-legged sitting on the presence of a lordotic lumbar posture in 22 non-ambulant boys and young men. Results: The boys and young men had a mean (SD) age of 15.1 (4.0) years, had been non-ambulant for 48.6 (33.8) months and used a median of 3.5 (range 2 to 7) postures a day. The mean Cobb angle was 15.1 (range 0 to 70) degrees. Optimal accuracy in predicting scoliosis was obtained with a lumbar angle of -6° as measured by skin markers, and both a lumbar angle ≤-6° (P=0.112) and better functional ability (P=0.102) were associated with less scoliosis. Use of cross-legged sitting postures during the day was associated with a lumbar angle ≤-6° (OR 0.061; 95% CI 0.005 - 0.672; P=0.022). Conclusions: Use of cross-legged sitting posture was associated with increase in lumbar lordosis. Higher angle of lumbar lordosis and better functional ability are associated with lesser degree of scoliosis

Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus

A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing repertoire diversity has been implicated in the age-associated decline in CD8 T cell immunity. In this study, using the well-characterized mouse influenza virus model, we show that although comparable numbers of CD8 T cells are elicited in the lung and lung airways of young and aged mice after de novo infection, a majority of aged mice exhibit profound shifts in epitope immunodominance and restricted diversity in the TCR repertoire of responding cells. A preferential decline in reactivity to viral epitopes with a low naive precursor frequency was observed, in some cases leading to “holes” in the T cell repertoire. These effects were also seen in young thymectomized mice, consistent with the role of the thymus in maintaining naive repertoire diversity. Furthermore, a decline in repertoire diversity generally correlated with impaired responses to heterosubtypic challenge. This study formally demonstrates in a mouse infection model that naturally occurring contraction of the naive T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes and decline in heterosubtypic immunity. These observations have important implications for the design of vaccine strategies for the elderly

Smelting conditions and smelting products: Experimental insights into the development of iron bloomery furnaces

The material record for bloomery furnaces in Iron Age and Roman Britain is fragmentary and, because of this paucity of evidence, the reconstruction of the ceramic structures used in iron production is difficult. Experiments have nevertheless been carried out to explore the working parameters and efficiency of iron smelting in bowl furnaces (small structures with little structure above ground level, interior measuring about 30 cm in height) (Craddock, 1995; Girbal, 2013) and shaft furnaces (height c.1m) (Smith, 2013; Crew, 2013; Doonan and Dungworth, 2013; Tylecote and Merkel, 1985; Tylecote and Wynne, 1958). These experiments aimed to clarify which furnace is more efficient for iron smelting and therefore what method was most likely used in Iron Age and Roman Britain. It is theorised that iron smelting furnaces developed from bowl structures to shaft structures over time, as smelters sought furnaces which could reach higher temperatures and create more reducing atmospheres (Dungworth 2013; Tylecote and Merkel, 1985; Tylecote and Wynne, 1958). These experiments suggest that the shaft furnace was used as it could meet these requirements. This study looks at the working conditions of a shaft furnace at an intermediary height - between that of a bowl furnace and of a shaft furnace - in order to understand its working parameters and to consequently better understand the progression from a bowl to a 1m high shaft structure

Mucosal Application of gp140 Encoding DNA Polyplexes to Different Tissues Results in Altered Immunological Outcomes in Mice

Increasing evidence suggests that mucosally targeted vaccines will enhance local humoral and cellular responses whilst still eliciting systemic immunity. We therefore investigated the capacity of nasal, sublingual or vaginal delivery of DNA-PEI polyplexes to prime immune responses prior to mucosal protein boost vaccination. Using a plasmid expressing the model antigen HIV CN54gp140 we show that each of these mucosal surfaces were permissive for DNA priming and production of antigen-specific antibody responses. The elicitation of systemic immune responses using nasally delivered polyplexed DNA followed by recombinant protein boost vaccination was equivalent to a systemic prime-boost regimen, but the mucosally applied modality had the advantage in that significant levels of antigen-specific IgA were detected in vaginal mucosal secretions. Moreover, mucosal vaccination elicited both local and systemic antigen-specific IgG(+) and IgA(+) antibody secreting cells. Finally, using an Influenza challenge model we found that a nasal or sublingual, but not vaginal, DNA prime/protein boost regimen protected against infectious challenge. These data demonstrate that mucosally applied plasmid DNA complexed to PEI followed by a mucosal protein boost generates sufficient antigen-specific humoral antibody production to protect from mucosal viral challenge

Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies