Modelling the variable broad-band optical/UV/X-ray spectrum of PG1211+143: Implications for the ionized outflow

We present the results from a detailed analysis of the 2007 Swift monitoring campaign of the quasar PG1211+143. We constructed broad-band, optical/UV/X-ray spectral energy distributions over three X-ray flux intervals. We fitted them with a model which accounts for the disc and the X-ray coronal emission and the warm absorber (well established in this source). The three flux spectra are well fitted by the model we considered. The disc inner temperature remains constant at ~2 eV, while X-rays are variable both in spectral slope and normalization. The absorber covers almost 90% of the central source. It is outflowing with a velocity less than 2.3*10^4 km/s (3sigma upper limit), and has a column density of ~10^23.2. Its ionization parameter varies by a factor of 1.6, and it is in photo-ionizing equilibrium with the ionizing flux. It is located at a distance of less than 0.35 pc from the central source and its relative thickness, DR/R is less than 0.1. The absorber' s ionization parameter variations can explain the larger than average amplitude of the X-ray variations. The absence of optical/UV variations (consistent with the high black hole mass estimate) argues against the presence of inward propagating disc fluctuations and strong X-ray illumination of the disc (in agreement with the low ratio of X-ray over the bolometric luminosity of ~20-35). We estimate an upper limit for the mass outflow of ~5 solar masses per year (~2.3 times the Eddington mass accretion rate). If the outflow rate is indeed that high, then it must be a short-lived episode in the quasar's life time. Finally, we estimate an upper limit for the kinetic power of the outflow of ~1.4*10^43 ergs/s. This outflow cannot deploy significant mechanical energy to the surrounding ISM of the quasar's host galaxy, but is sufficient to heat the ISM to 10^7 K and to produce a fast decline to the star formation rate of the galaxy.Comment: Accepted for publication by A&

Deciphering the signaling mechanisms of the plant cell wall degradation machinery in Aspergillus oryzae

published_or_final_versio

Integrated Text Mining and Chemoinformatics Analysis Associates Diet to Health Benefit at Molecular Level

published_or_final_versio

COMAN: a web server for comprehensive metatranscriptomics analysis

published_or_final_versio

Developing a Molecular Roadmap of Drug-Food Interactions

Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.published_or_final_versio

MESSI: metabolic engineering target selection and best strain identification tool

Metabolic engineering and synthetic biology are synergistically related fields for manipulating target pathways and designing microorganisms that can act as chemical factories. Saccharomyces cerevisiae’s ideal bioprocessing traits make yeast a very attractive chemical factory for production of fuels, pharmaceuticals, nutraceuticals as well as a wide range of chemicals. However, future attempts of engineering S. cerevisiae’s metabolism using synthetic biology need to move towards more integrative models that incorporate the high connectivity of metabolic pathways and regulatory processes and the interactions in genetic elements across those pathways and processes. To contribute in this direction, we have developed Metabolic Engineering target Selection and best Strain Identification tool (MESSI), a web server for predicting efficient chassis and regulatory components for yeast bio-based production. The server provides an integrative platform for users to analyse ready-to-use public high-throughput metabolomic data, which are transformed to metabolic pathway activities for identifying the most efficient S. cerevisiae strain for the production of a compound of interest. As input MESSI accepts metabolite KEGG IDs or pathway names. MESSI outputs a ranked list of S. cerevisiae strains based on aggregation algorithms. Furthermore, through a genome-wide association study of the metabolic pathway activities with the strains’ natural variation, MESSI prioritizes genes and small variants as potential regulatory points and promising metabolic engineering targets. Users can choose various parameters in the whole process such as (i) weight and expectation of each metabolic pathway activity in the final ranking of the strains, (ii) Weighted AddScore Fuse or Weighted Borda Fuse aggregation algorithm, (iii) type of variants to be included, (iv) variant sets in different biological levels. Database URL: http://sbb.hku.hk/MESSI

Ethical and practical challenges in implementing informed consent in HIV/AIDS clinical trials in developing or resource-limited countries

Background/rationale: Ethical issues regarding HIV/AIDS human research in the developing world remain under continuous evaluation; a critical area of concern includes informed consent. This paper reviews several of the most important ethical and practical aspects of informed consent in HIV research in developing countries. Enhancement of overall understanding of such key issues might promote higher ethical standards of future research.Objectives: The major objective was to address informed consent in human research in non-Western societies, and specifically in HIV clinical trials of affected adults. Secondary end-points included the consent complexities in HIV research involving vulnerable patient populations in resource-limited nations, such as children, adolescents and women.Methods: A systematic review of the published literature using MEDLINE and EMBASE from 1998 until December 2008 was performed, using the search terms ‘HIV/AIDS’, ‘informed consent’, ‘clinical trials’, ‘developing world’.Results: Ethical complexities such as participants’ diminished autonomy, coercion or monetary inducement, language difficulties, illiteracy or lack of true understanding of the entire study, cultural barriers mainly due to communitarianism and social diversities were identified in the 44 studies reviewed. Informed consent of vulnerable patient populations must be tailored to their sex and developmental age, while counselling is fundamental. Children and adolescents’ assent must be ensured. Local language is to be used, while trusted community leaders and local cultural representatives may convey information.Discussion: Despite the heterogeneity of studies, similarities were  identified. Providing adequate and comprehensive information and assessing the true understanding of the research represent fundamental prerequisites. Potential solutions to the critical areas of concern include peer counselling and meetings with local community leaders or local cultural representatives. Conclusions: International investigators of HIV human research should bear in mind these ethical issues and their potential solutions, when trying to ensure ethical research conduct, based on a truly informed and culturally relevant consent

Revisiting UV/optical continuum time lags in AGN

In this paper, we present an updated version of our model (KYNXiltr) which considers thermal reverberation of a standard Novikov-Thorne accretion disc illuminated by an X-ray point-like source. Previously, the model considered only two cases of black hole spins, and assumed a colour correction factor $f_{\rm col} = 2.4$. Now, we extend the model to any spin value and colour correction. In addition, we consider two scenarios of powering the X-ray corona, either via accretion, or external to the accretion disc. We use KYNXiltr to fit the observed time lags obtained from intense monitoring of four local Seyfert galaxies (NGC 5548, NGC 4395, Mrk 817, and Fairall 9). We consider various combinations of black hole spin, colour correction, corona height, and fraction of accretion power transferred to the corona. The model fits well the overall time-lags spectrum in these sources (for a large parameter space). For NGC 4593 only, we detect a significant excess of delays in the U-band. The contribution of the diffuse BLR emission in the time-lags spectrum of this source is significant. It is possible to reduce the large best-fitting parameter space by combining the results with additional information, such as the observed Eddington ratio and average X-ray luminosity. We also provide an update to the analytic expression provided by Kammoun et al., for an X-ray source that is not powered by the accretion process, which can be used for any value of colour correction, and for two values of the black hole spin (0 and 0.998).Comment: Accepted for publication in MNRA