ArrayIDer: automated structural re-annotation pipeline for DNA microarrays

<p>Abstract</p> <p>Background</p> <p>Systems biology modeling from microarray data requires the most contemporary structural and functional array annotation. However, microarray annotations, especially for non-commercial, non-traditional biomedical model organisms, are often dated. In addition, most microarray analysis tools do not readily accept EST clone names, which are abundantly represented on arrays. Manual re-annotation of microarrays is impracticable and so we developed a computational re-annotation tool (<it>ArrayIDer</it>) to retrieve the most recent accession mapping files from public databases based on EST clone names or accessions and rapidly generate database accessions for entire microarrays.</p> <p>Results</p> <p>We utilized the Fred Hutchinson Cancer Research Centre 13K chicken cDNA array – a widely-used non-commercial chicken microarray – to demonstrate the principle that <it>ArrayIDer </it>could markedly improve annotation. We structurally re-annotated 55% of the entire array. Moreover, we decreased non-chicken functional annotations by 2 fold. One beneficial consequence of our re-annotation was to identify 290 pseudogenes, of which 66 were previously incorrectly annotated.</p> <p>Conclusion</p> <p><it>ArrayIDer </it>allows rapid automated structural re-annotation of entire arrays and provides multiple accession types for use in subsequent functional analysis. This information is especially valuable for systems biology modeling in the non-traditional biomedical model organisms.</p

Senile Systemic Amyloidosis: Clinical Features at Presentation and Outcome

Background Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac‐isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors. Methods and Results All patients with biopsy‐proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N‐terminal pro‐B‐type natriuretic peptide (NT pro‐BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro‐BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro‐BNP <1420 pmol/L. Conclusions Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro‐BNP level can aid in distinguishing ATTRwt from AL amyloidosis

Controlling the Optical Properties of a Conjugated Co-polymer through Variation of Backbone Isomerism and the Introduction of Carbon Nanotubes

The need to control the formation of weakly emitting species in polymers such as aggregates and excimers, which are normally detrimental to device performance, is illustrated for the example of the polymer poly(m-phenylenevinylene-co-2,5-dioctyloxy-p-phenylenevinylene), using the model compound, 2,5-dioctyloxy-p-distyrylbenzene as a comparison. Two different methods, namely a Homer-Emmons polycondensation in dimethylformamide (DMF) and a Wittig polycondensation in dry toluene, have been used during synthesis resulting in a polymer with a predominantly trans-vinylene backbone and a polymer with a predominantly cis-vinylene backbone, respectively. Photoluminescence and absorption spectroscopy indicate that the polymer forms aggregate species in solution with spectra that are distinctly red-shifted from those associated with the intra-chain exciton. Concentration dependent optical studies were used to probe the evolution of aggregation in solution for both polymers. The results indicate that inter-chain coupling in the predominantly cis-polymer is prominent at lower concentrations than in the case of the trans-counterpart. These results are supported by pico-second pump and probe transient absorption measurements where, in dilute solutions, the polymer in a cis-configuration exhibits highly complex excited state dynamics, whereas the polymer in a trans-configuration behaves similarly to the model compound. It is proposed therefore that the degree of backbone isomerism has a profound impact on the morphology of the polymeric solid and control over it is a route towards optimising the performance of the material in thin film form. Another method to inhibit inter-chain effects using multi walled carbon nanotubes (MWNT) as nano-spacers in the polymer solutions is proposed. By comparison to spectroscopic analysis, aggregation effects are shown to be reduced by the introduction of nanotubes. Electron microscopy and computer simulation suggest a well-defined interaction between the polymer backbone and the lattice of the nanotube

Extended RDF: Computability and Complexity Issues

ERDF stable model semantics is a recently proposed semantics for ERDF ontologies and a faithful extension of RDFS semantics on RDF graphs. In this paper, we elaborate on the computability and complexity issues of the ERDF stable model semantics. Based on the undecidability result of ERDF stable model semantics, decidability under this semantics cannot be achieved, unless ERDF ontologies of restricted syntax are considered. Therefore, we propose a slightly modified semantics for ERDF ontologies, called ERDF #n- stable model semantics. We show that entailment under this semantics is, in general, decidable and also extends RDFS entailment. Equivalence statements between the two semantics are provided. Additionally, we provide algorithms that compute the ERDF #n-stable models of syntax-restricted and general ERDF ontologies. Further, we provide complexity results for the ERDF #nstable model semantics on syntax-restricted and general ERDF ontologies. Finally, we provide complexity results for the ERDF stable model semantics on syntax-restricted ERDF ontologies

Improving the use of research evidence in guideline development: introduction

In 2005 the World Health Organisation (WHO) asked its Advisory Committee on Health Research (ACHR) for advice on ways in which WHO can improve the use of research evidence in the development of recommendations, including guidelines and policies. The ACHR established the Subcommittee on the Use of Research Evidence (SURE) to collect background documentation and consult widely among WHO staff, international experts and end users of WHO recommendations to inform its advice to WHO. We have prepared a series of reviews of methods that are used in the development of guidelines as part of this background documentation. We describe here the background and methods of these reviews, which are being published in Health Research Policy and Systems together with this introduction

Prevalence of multimorbidity and its association with outcomes in older emergency general surgical patients : an observational study

Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.Peer reviewedPublisher PD

The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Pressure dependent electronic properties of MgO polymorphs: A first-principles study of Compton profiles and autocorrelation functions

The first-principles periodic linear combination of atomic orbitals method within the framework of density functional theory implemented in the CRYSTAL06 code has been applied to explore effect of pressure on the Compton profiles and autocorrelation functions of MgO. Calculations are performed for the B1, B2, B3, B4, B8_1 and h-MgO polymorphs of MgO to compute lattice constants and bulk moduli. The isothermal enthalpy calculations predict that B4 to B8_1, h-MgO to B8_1, B3 to B2, B4 to B2 and h-MgO to B2 transitions take place at 2, 9, 37, 42 and 64 GPa respectively. The high pressure transitions B8_1 to B2 and B1 to B2 are found to occur at 340 and 410 GPa respectively. The pressure dependent changes are observed largely in the valence electrons Compton profiles whereas core profiles are almost independent of the pressure in all MgO polymorphs. Increase in pressure results in broadening of the valence Compton profiles. The principal maxima in the second derivative of Compton profiles shifts towards high momentum side in all structures. Reorganization of momentum density in the B1 to B2 structural phase transition is seen in the first and second derivatives before and after the transition pressure. Features of the autocorrelation functions shift towards lower r side with increment in pressure.Comment: 19 pages, 8 figures, accepted for publication in Journal of Materials Scienc

Challenges in Developing Evidence-Based Recommendations Using the GRADE Approach: The Case of Mental, Neurological, and Substance Use Disorders

Corrado Barbui and colleagues describe their use and adaptation of the GRADE approach in developing the guidelines for the WHO mental health Gap Action Programme (mhGAP)