Large-vocabulary speaker-independent continuous speech recognition with semi-continuous hidden Markov models

A semi-continuous hidden Markov model based on the muluple vector quantization codebooks is used here for large.vocabulary speaker-independent continuous speech recognition in the techn,ques employed here. the semi-continuous output probab~hty densHy function for each codebook is represented by a comhinat,on of the corre,~ponding discrete output probablhttes of the hidden Markov model end the continuous Gauss,an den. stay functions of each individual codebook. Parameters of vec. tor qusnttzation codebook and hidden Markov model are mutuully optimized to achJeve an optimal model'codebook comb,nation under a untried probab,hshc framework Another advantages of thts approach is the enhanced robustness of the semi. continuous output probability by the combination of multiple codewords and multtple codebooks For a 1000.word speakermdependen

Compressed Data Structures for Dynamic Sequences

We consider the problem of storing a dynamic string $S$ over an alphabet $\Sigma=\{\,1,\ldots,\sigma\,\}$ in compressed form. Our representation supports insertions and deletions of symbols and answers three fundamental queries: $\mathrm{access}(i,S)$ returns the $i$-th symbol in $S$, $\mathrm{rank}_a(i,S)$ counts how many times a symbol $a$ occurs among the first $i$ positions in $S$, and $\mathrm{select}_a(i,S)$ finds the position where a symbol $a$ occurs for the $i$-th time. We present the first fully-dynamic data structure for arbitrarily large alphabets that achieves optimal query times for all three operations and supports updates with worst-case time guarantees. Ours is also the first fully-dynamic data structure that needs only $nH_k+o(n\log\sigma)$ bits, where $H_k$ is the $k$-th order entropy and $n$ is the string length. Moreover our representation supports extraction of a substring $S[i..i+\ell]$ in optimal $O(\log n/\log\log n + \ell/\log_{\sigma}n)$ time

The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun

© 2020 The Author(s). Background: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells. Methods: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species. Results: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC). Conclusions: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action

Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review

Background: Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. Methods/design: The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, Econ Lit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. Discussion: The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this

Intraspecies diversity of SARS-like coronaviruses in Rhinolophus sinicus and its implications for the origin of SARS coronaviruses in humans

The Chinese rufous horseshoe bat (Rhinolophus sinicus) has been suggested to carry the direct ancestor of severe acute respiratory syndrome (SARS) coronavirus (SCoV), and the diversity of SARS-like CoVs (SLCoV) within this Rhinolophus species is therefore worth investigating. Here, we demonstrate the remarkable diversity of SLCoVs in R. sinicus and identify a strain with the same pattern of phylogenetic incongruence (i.e. an indication of recombination) as reported previously in another SLCoV strain. Moreover, this strain possesses a distinctive 579 nt deletion in the nsp3 region that was also found in a human SCoV from the late-phase epidemic. Phylogenetic analysis of the Orf1 region suggested that the human SCoVs are phylogenetically closer to SLCoVs in R. sinicus than to SLCoVs in other Rhinolophus species. These findings reveal a closer evolutionary linkage between SCoV in humans and SLCoVs in R. sinicus, defining the scope of surveillance to search for the direct ancestor of human SCoVs. © 2010 SGM.published_or_final_versio

Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities

E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities

Sceptical Employees as CSR Ambassadors in Times of Financial Uncertainty

This chapter offers new insights into the understanding of internal (employee) perceptions of organizational corporate social responsibility (CSR) policies and strategies. This study explores the significance of employees’ involvement and scepticism upon CSR initiatives and focuses on the effects it may have upon word of mouth (WOM) and the development of employee–organisation relationships. Desk research introduces the research questions. Data for the research questions were gathered through a self-completion questionnaire distributed in a hardcopy form to the sample. An individual’s level of scepticism and involvement appears to affect the development of a positive effect on employees’ WOM. Involvement with the domain of the investment may be a central factor affecting relationship building within the organization, and upon generation of positive WOM. The chapter offers a conceptual framework to public relations (PR) and corporate communications practitioners, which may enrich their views and understanding of the use and value of CSR for communication strategies and practices. For-profit organisations are major institutions in today’s society. CSR is proffered as presenting advantages for (at macro level) society and (micro level) the organization and its employees. Concepts, such as involvement and scepticism, which have not been rigorously examined in PR and corporate communication literature, are addressed. By examining employee perceptions, managers and academic researchers gain insights into the acceptance, appreciation and effectiveness of CSR policies and activities upon the employee stakeholder group. This will affect current and future CSR communication strategies. The knowledge acquired from this chapter may be transferable outside the for-profit sector