474 research outputs found

    Bilinear probabilistic principal component analysis

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    Probabilistic principal component analysis (PPCA) is a popular linear latent variable model for performing dimension reduction on 1-D data in a probabilistic manner. However, when used on 2-D data such as images, PPCA suffers from the curse of dimensionality due to the subsequently large number of model parameters. To overcome this problem, we propose in this paper a novel probabilistic model on 2-D data called bilinear PPCA (BPPCA). This allows the establishment of a closer tie between BPPCA and its nonprobabilistic counterpart. Moreover, two efficient parameter estimation algorithms for fitting BPPCA are also developed. Experiments on a number of 2-D synthetic and real-world data sets show that BPPCA is more accurate than existing probabilistic and nonprobabilistic dimension reduction methods.published_or_final_versio

    Genetic Code Mutations: The Breaking of a Three Billion Year Invariance

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    The genetic code has been unchanging for some three billion years in its canonical ensemble of encoded amino acids, as indicated by the universal adoption of this ensemble by all known organisms. Code mutations beginning with the encoding of 4-fluoro-Trp by Bacillus subtilis, initially replacing and eventually displacing Trp from the ensemble, first revealed the intrinsic mutability of the code. This has since been confirmed by a spectrum of other experimental code alterations in both prokaryotes and eukaryotes. To shed light on the experimental conversion of a rigidly invariant code to a mutating code, the present study examined code mutations determining the propagation of Bacillus subtilis on Trp and 4-, 5- and 6-fluoro-tryptophans. The results obtained with the mutants with respect to cross-inhibitions between the different indole amino acids, and the growth effects of individual nutrient withdrawals rendering essential their biosynthetic pathways, suggested that oligogenic barriers comprising sensitive proteins which malfunction with amino acid analogues provide effective mechanisms for preserving the invariance of the code through immemorial time, and mutations of these barriers open up the code to continuous change

    Seroprevalence of antibody to pandemic influenza A (H1N1) 2009 among healthcare workers after the first wave in Hong Kong

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    During the first wave of an influenza pandemic prior to the availability of an effective vaccine, healthcare workers (HCWs) may be at particular risk of infection with the novel influenza strain. We conducted a cross-sectional study of the prevalence of antibody to pandemic influenza A (H1N1) 2009 (pH1N1) among HCWs in Hong Kong in February-March 2010 following the first pandemic wave. Sera collected from HCWs were tested for antibody to pH1N1 influenza virus by viral neutralisation (VN). We assessed factors associated with higher antibody titres, and we compared antibody titres in HCWs with those in a separate community study. In total we enrolled 703 HCWs. Among 599 HCWs who did not report receipt of pH1N1 vaccine, 12% had antibody titre ≥1:40 by VN. There were no significant differences in the age-specific proportions of unvaccinated HCWs with antibody titre ≥1:40 compared with the general community following the first wave of pH1N1. Under good adherence to infection control guidelines, potential occupational exposures in the hospital setting did not appear to be associated with any substantial excess risk of pH1N1 infection in HCWs. Most HCWs had low antibody titres following the first pandemic wave. © 2011 The Healthcare Infection Society.postprin

    Education research in Australia: where is it conducted?

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    Research assessment exercises aim to identify research quantity and quality and provide insights into research capacity building strategies for the future. Yet with limited knowledge of the ecology of Australian educational research, there is little chance of understanding what research audits might contribute towards a capacity building agenda for such a complex field. This paper draws on secondary data analysis of research outputs submitted by 13 Australian higher education institutions to the Excellence in Research for Australia (ERA) 2010 and 2012 national research assessment exercises, to show where Australian educational research is conducted. Findings offer a profile of education researchers by location in academic organisational units within universities. By analyzing data not accessible through reported ERA data we were also able to present information about appointment profiles, specifically levels and type of appointment within universities, as well as data on institutional and geographic region, and patterns associated with type of outputs (books, book chapters, journal articles, conference papers and other outputs) and field of research. Analysis of the data reveals definitive shifts in the nature of the published outputs and in employment profiles of researchers and their location across university and regional groupings. Research audits are administrative processes that reshape institutional and disciplinary governance structures, policies, individual outputs, work practices and careers, but they are not the sum total of the field per se

    Time-resolved spectroscopy studies of the photodeprotection reactions of p-hydroxyphenacyl ester phototrigger compounds

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    Ultrafast time-resolved spectroscopy and time-resolved resonance Raman spectroscopy experimental results in the picoseocond timescales are reported for selected p-hydroxyphenacyl (pHP) ester phototrigger compounds. The results better elucidate the photodeprotection and rearrangement reactions of these important phototriggers and an overall mechanism is proposed for these reactions based on the time-resolved spectroscopy data presented here. This work indicates that site-specific, concerted solvation of the hydroxy proton and phosphate-leaving anion group through their respective intermolecular H-bonding with solvent water molecules promotes the photodeprotection reaction.published_or_final_versio

    Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

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    Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

    Relationship between galactomannan structure and physicochemical properties of films produced thereof

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    In this work five sources of galactomannans, Adenanthera pavonina, Cyamopsis tetragonolobus, Caesalpinia pulcherrima, Ceratonia siliqua and Sophora japonica, presenting mannose/galactose ratios of 1.3, 1.7, 2.9, 3.4 and 5.6, respectively, were used to produce galactomannan-based films. These films were characterized in terms of: water vapour, oxygen and carbon dioxide permeabilities (WVP, O 2 P and CO 2 P); moisture content, water solubility, contact angle, elongation-at-break (EB), tensile strength (TS) and glass transition temperature (T g ). Results showed that films properties vary according to the galactomannan source (different galactose distribution) and their mannose/galactose ratio. Water affinity of mannan and galactose chains and the intermolecular interactions of mannose backbone should also be considered being factors that affect films properties. This work has shown that knowing mannose/galactose ratio of galactomannans is possible to foresee galactomannan-based edible films properties.The authors thank the fellowship (SFRH/BPD/ 72753/2010) from the Fundação para a Ciência e Tecnologia (FCT, Portugal). The authors also thank the FCT Strategic Project of UID/BIO/ 04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-010124-FEDER-027462) and the project BBioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-000028 Co-funded by the Programa OperacionalRegionaldoNorte(ON.2–ONovoNorte),QREN,FEDER. Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico – FUNCAP, CE Brazil (CI1-0080-00055.01.00/13)

    Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong

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    We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.postprin

    Is respiratory viral infection really an important trigger of asthma exacerbations in children?

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    We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. One hundred and fourteen children aged 6–14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment. They would attend the study clinic if peak expiratory flow rate decreased to below 80% of their baselines, if they met a predefined symptom score, or if parents subjectively felt them developing a cold. Virological diagnosis using virus culture, antigen detection, and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers. Physician diagnosed outcome of each episode was documented. Three hundred and five episodes of respiratory illnesses were captured in the cohort. Nasal specimens were available in 166 episodes, 92 of which were diagnosed as asthma exacerbations, and 74 non-asthma related episodes. Respiratory viruses were detected in 61 of 166 episodes (36.7%). There was no significant difference in virus detection rate between asthma exacerbations (32 out of 97 episodes, 34.8%) and non-asthma respiratory illnesses (29 out of 79 episodes, 39.2%). Although newly discovered respiratory viruses were identified in these episodes, rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. We conclude that not all viral infections in children with asthma lead to an asthma exacerbation and the attributing effect of different triggers of asthma exacerbations in children vary across different time periods and across different localities

    Modelling the Proportion of Influenza Infections within Households during Pandemic and Non-Pandemic Years

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    Background: The key epidemiological difference between pandemic and seasonal influenza is that the population is largely susceptible during a pandemic, whereas, during non-pandemic seasons a level of immunity exists. The population-level efficacy of household-based mitigation strategies depends on the proportion of infections that occur within households. In general, mitigation measures such as isolation and quarantine are more effective at the population level if the proportion of household transmission is low. Methods/Results: We calculated the proportion of infections within households during pandemic years compared with non-pandemic years using a deterministic model of household transmission in which all combinations of household size and individual infection states were enumerated explicitly. We found that the proportion of infections that occur within households was only partially influenced by the hazard h of infection within household relative to the hazard of infection outside the household, especially for small basic reproductive numbers. During pandemics, the number of within-household infections was lower than one might expect for a given h because many of the susceptible individuals were infected from the community and the number of susceptible individuals within household was thus depleted rapidly. In addition, we found that for the value of h at which 30% of infections occur within households during non-pandemic years, a similar 31% of infections occur within households during pandemic years. Interpretation: We suggest that a trade off between the community force of infection and the number of susceptible individuals in a household explains an apparent invariance in the proportion of infections that occur in households in our model. During a pandemic, although there are more susceptible individuals in a household, the community force of infection is very high. However, during non-pandemic years, the force of infection is much lower but there are fewer susceptible individuals within the household. © 2011 Kwok et al.published_or_final_versio
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