Unsupervised crosslingual adaptation of tokenisers for spoken language recognition

Phone tokenisers are used in spoken language recognition (SLR) to obtain elementary phonetic information. We present a study on the use of deep neural network tokenisers. Unsupervised crosslingual adaptation was performed to adapt the baseline tokeniser trained on English conversational telephone speech data to different languages. Two training and adaptation approaches, namely cross-entropy adaptation and state-level minimum Bayes risk adaptation, were tested in a bottleneck i-vector and a phonotactic SLR system. The SLR systems using the tokenisers adapted to different languages were combined using score fusion, giving 7-18% reduction in minimum detection cost function (minDCF) compared with the baseline configurations without adapted tokenisers. Analysis of results showed that the ensemble tokenisers gave diverse representation of phonemes, thus bringing complementary effects when SLR systems with different tokenisers were combined. SLR performance was also shown to be related to the quality of the adapted tokenisers

Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures.

Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan-cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis-defined CNA signatures are predictive of glycolytic phenotypes, including 18F-fluorodeoxy-glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer-linked metabolic enzymes. A pan-cancer and cross-species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer-driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution

Unsupervised crosslingual adaptation of tokenisers for spoken language recognition

Phone tokenisers are used in spoken language recognition (SLR) to obtain elementary phonetic information. We present a study on the use of deep neural network tokenisers. Unsupervised crosslingual adaptation was performed to adapt the baseline tokeniser trained on English conversational telephone speech data to different languages. Two training and adaptation approaches, namely cross-entropy adaptation and state-level minimum Bayes risk adaptation, were tested in a bottleneck i-vector and a phonotactic SLR system. The SLR systems using the tokenisers adapted to different languages were combined using score fusion, giving 7-18% reduction in minimum detection cost function (minDCF) compared with the baseline configurations without adapted tokenisers. Analysis of results showed that the ensemble tokenisers gave diverse representation of phonemes, thus bringing complementary effects when SLR systems with different tokenisers were combined. SLR performance was also shown to be related to the quality of the adapted tokenisers

Physiological Fluid Flow Moderates Fibroblast Responses to TGF-β1.

Fibroblasts are the major cellular component of connective tissue and experience mechanical perturbations due to matrix remodelling and interstitial fluid movement. Transforming growth factor β1 (TGF-β1) can promote differentiation of fibroblasts in vitro to a contractile myofibroblastic phenotype characterised by the presence of α-smooth muscle actin (α-SMA) rich stress fibres. To study the role of mechanical stimulation in this process, we examined the response of primary human fibroblasts to physiological levels of fluid movement and its influence on fibroblast differentiation and responses to TGF-β1. We report that in both oral and dermal fibroblasts, physiological levels of fluid flow induced widespread changes in gene expression compared to static cultures, including up-regulation of genes associated with TGFβ signalling and endocytosis. TGF-β1, activin A and markers of myofibroblast differentiation including α-SMA and collagen IA1 were also increased by flow but surprisingly the combination of flow and exogenous TGF-β1 resulted in reduced differentiation. Our findings suggest this may result from enhanced internalisation of caveolin and TGF-β receptor II. These findings suggest that a) low levels of fluid flow induce myofibroblast differentiation and b) fluid flow antagonises the fibroblast response to pro-differentiation signals such as TGF-β1. We propose that this may be a novel mechanism by which mechanical forces buffer responses to chemical signals in vivo, maintaining a context-specific fibroblast phenotype. This article is protected by copyright. All rights reserved

Diffuse panbronchiolitis: not just an Asian disease: Australian case series and review of the literature

Diffuse panbronchiolitis is a disease of obscure aetiology that is traditionally associated with Asian ethnicity. We propose that this disease also occurs in Caucasians and the incidence in this population is greater than currently recognised. We further propose that high resolution computed tomography (HRCT) and response to macrolide therapy should be relied upon to make this diagnosis without verification by lung biopsy. In most circumstances, obtaining a biopsy for histopathology is not practical, and the disease may then be mistaken for other more common airway diseases. Accuracy of diagnosis is important as untreated disease is associated with a poor prognosis, and effective treatment is available. We report four out of a series of cases as evidence that DPB is in fact more common in the Western population than is currently understood

A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)

Background: In order to facilitate implementation of precision medicine in clinical management of cancer, there is a need to harmonise and standardise the reporting and interpretation of clinically relevant genomics data. / Methods: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to propose a classification system for molecular aberrations based on the evidence available supporting their value as clinical targets. A group of experts from several institutions was assembled to review available evidence, reach a consensus on grading criteria and present a classification system. This was then reviewed, amended and finally approved by the ESMO TR and PM WG and the ESMO leadership. / Results: This first version of the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT) defines six levels of clinical evidence for molecular targets according to the implications for patient management: tier I, targets ready for implementation in routine clinical decisions; tier II, investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed; tier III, clinical benefit previously demonstrated in other tumour types or for similar molecular targets; tier IV, preclinical evidence of actionability; tier V, evidence supporting co-targeting approaches; and tier X, lack of evidence for actionability. / Conclusions: The ESCAT defines clinical evidence-based criteria to prioritise genomic alterations as markers to select patients for targeted therapies. This classification system aims to offer a common language for all the relevant stakeholders in cancer medicine and drug development

Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodeling

The renin angiotensin system (RAS) is integral to cardiovascular physiology, however, dysregulation of this system largely contributes to the pathophysiology of cardiovascular disease (CVD). It is well established that angiotensin II (Ang II), the main effector of the RAS, engages the angiotensin type 1 receptor and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodeling of the heart and vasculature, ultimately leading to the development and progression of various CVDs including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centered on the actions of angiotensin converting enzyme 2 (ACE2) and the resultant production of angiotensin-(1-7) (Ang-(1-7) from Ang II, antagonizes the actions of Ang II via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9), has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. This review will discuss the role of the counter-regulatory RAS peptides, Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodeling of the heart and vasculature

Information security awareness at the knowledge-based institution: its antecedents and measures

Information security awareness (ISA) is referred to as a state of consciousness where user ideally committed to the rules, recognize the potentiality, understand the importance of responsibilities and act accordingly. Despite the number of case occurred in information security breaches, especially at knowledge-based institution result from the reluctance of user's failure to comply with security guidelines, such effective measure should take place to anticipate the negative effect. Therefore, more attention is required to understand the roles of individual, institutional and environmental antecedent for optimization in raising the information security awareness. This paper elucidated the roles of its antecedent and measure in influencing ISA of user using survey method that contributes for better understanding by analyzing user perception. From the result, this study identified several important factor impacts to the awareness and its relationship to other factor such as religious indicator can influence peer performance but also social pressure. Thus higher education can focus the policy for encouraging them to have proper response from student and staff in avoiding security incident

Deleted in Liver Cancer 2 (DLC2) Was Dispensable for Development and Its Deficiency Did Not Aggravate Hepatocarcinogenesis

DLC2 (deleted in liver cancer 2), a Rho GTPase-activating protein, was previously shown to be underexpressed in human hepatocellular carcinoma and has tumor suppressor functions in cell culture models. We generated DLC2-deficient mice to investigate the tumor suppressor role of DLC2 in hepatocarcinogenesis and the function of DLC2 in vivo. In this study, we found that, unlike homologous DLC1, which is essential for embryonic development, DLC2 was dispensable for embryonic development and DLC2-deficient mice could survive to adulthood. We also did not observe a higher incidence of liver tumor formation or diethylnitrosamine (DEN)-induced hepatocarcinogenesis in DLC2-deficient mice. However, we observed that DLC2-deficient mice were smaller and had less adipose tissue than the wild type mice. These phenotypes were not due to reduction of cell size or defect in adipogenesis, as observed in the 190B RhoGAP-deficient mouse model. Together, these results suggest that deficiency in DLC2 alone does not enhance hepatocarcinogenesis