Tuberculosis - Reaping benefits from COVID-19 in Portugal

CommentNo additional funding sources are to be declared

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

Left-right breast asymmetry and risk of screen-detected and interval cancers in a large population-based screening population

OBJECTIVES: To assess the associations between automated volumetric estimates of mammographic asymmetry and breast cancers detected at the same ("contemporaneous") screen, at subsequent screens, or in between (interval cancers). METHODS: Automated measurements from mammographic images (N = 79,731) were used to estimate absolute asymmetry in breast volume (BV) and dense volume (DV) in a large ethnically diverse population of attendees of a UK breast screening programme. Logistic regression models were fitted to assess asymmetry associations with the odds of a breast cancer detected at contemporaneous screen (767 cases), adjusted for relevant confounders.Nested case-control investigations were designed to examine associations between asymmetry and the odds of: (a) interval cancer (numbers of cases/age-matched controls: 153/646) and (b) subsequent screen-detected cancer (345/1438), via conditional logistic regression. RESULTS: DV, but not BV, asymmetry was positively associated with the odds of contemporaneous breast cancer (P-for-linear-trend (Pt) = 0.018). This association was stronger for first (prevalent) screens (Pt = 0.012). Both DV and BV asymmetry were positively associated with the odds of an interval cancer diagnosis (Pt = 0.060 and 0.030, respectively). Neither BV nor DV asymmetry were associated with the odds of having a subsequent screen-detected cancer. CONCLUSIONS: Increased DV asymmetry was associated with the risk of a breast cancer diagnosis at a contemporaneous screen or as an interval cancer. BV asymmetry was positively associated with the risk of an interval cancer diagnosis. ADVANCES IN KNOWLEDGE: The findings suggest that DV and BV asymmetry may provide additional signals for detecting contemporaneous cancers and assessing the likelihood of interval cancers in population-based screening programmes

Are mammography image acquisition factors, compression pressure and paddle tilt, associated with breast cancer detection in screening?

Objectives: To assess the associations between objectively measured mammographic compression pressure and paddle tilt and breast cancer (BC) detected at the same (“contemporaneous”) screen, subsequent screens, or in-between screens (interval cancers). Methods: Automated pressure and paddle tilt estimates were derived for 80,495 mammographic examina-tions in a UK population-based screening programme. Adjusted logistic regression models were fitted to estimate the associations of compression parameters with BC detected at contemporaneous screen (777 cases). Nested case-control designs were used to estimate associations of pressure and tilt with: (a) interval cancer (148 cases/625 age-matched controls) and (b) subsequent screen-detected cancer (344/1436), via condi-tional logistic regression. Results: Compression pressure was negatively associated with odds of BC at contemporaneous screen (odds ratio (OR) for top versus bottom third of the pressure distribution: 0.74; 95% CI 0.60, 0.92; P-for-linear-trend (Pt) = 0.007). There was weak evidence that moderate pressure at screening was associated with lower odds of interval cancer (OR for middle versus bottom third: 0.63; 95% CI 0.38, 1.05; p = 0.079), but no association was found between pressure and the odds of BC at subsequent screen. There was no evidence that paddle tilt was associated with the odds of contemporaneous, subsequent screen or interval cancer detection. Conclusions: Findings are consistent with compression pressure, but not paddle tilt, affecting the performance of mammographic screening by interfering with its ability to detect cancers. Advances in knowledge: Inadequate or excessive compression pressure at screening may contribute to a reduced ability to detect cancers, resulting in a greater number of interval cancer cases

Fermentation kinetics including product and substrate inhibitions plus biomass death: a mathematical analysis

Fermentation is generally modelled by kinetic equations giving the time evolutions for biomass, substrate, and product concentrations. Although these equations can be solved analytically in simple cases if substrate/product inhibition and biomass death are included, they are typically solved numerically. We propose an analytical treatment of the kinetic equations --including cell death and an arbitrary number of inhibitions-- in which constant yield needs not be assumed. Equations are solved in phase space, i.e. the biomass concentration is written explicitly as a function of the substrate concentration.Comment: 4 pages, 4 figure

Student and staff perceptions and experiences of the introduction of Objective Structured Practical Examinations: A pilot study

Background. The Objective Structured Practical Examination (OSPE) is widely recognised as one of the more objective methods of assessing practical skills in healthcare programmes, including undergraduate physiotherapy curricula.Objectives. To obtain feedback from both students and staff who were involved in the introduction of an OSPE in 2011, in order to refine and standardise the format throughout the curriculum.Methods. A qualitative research design was used. Data were gathered through a questionnaire with semi-structured open-ended items and focus group discussion. Participants were all third-year undergraduate physiotherapy students (N=47) and all staff members (N=10) in the 2011 academic year who were exposed to the OSPE format or were involved in the first OSPE.Results. The main concerns raised by both students and staff were: (i) pressure due to time constraints and how this might affect student performance; and (ii) the question of objectivity during the assessment. However, their initial concerns changed as they experienced the OSPE in a more positive manner owing to the structure and objectivity of the process of implementing the OSPE.Conclusion. While both students and staff reported positive experiences, the challenges that emerged provided valuable insight in terms of refining the OSPE format in this undergraduate physiotherapy department

Comparison of Newtonian and Special-Relativistic Trajectories with the General-Relativistic Trajectory for a Low-Speed Weak-Gravity System

We show, contrary to expectation, that the trajectory predicted by general-relativistic mechanics for a low-speed weak-gravity system is not always well-approximated by the trajectories predicted by special-relativistic and Newtonian mechanics for the same parameters and initial conditions. If the system is dissipative, the breakdown of agreement occurs for chaotic trajectories only. If the system is non-dissipative, the breakdown of agreement occurs for chaotic trajectories and non-chaotic trajectories. The agreement breaks down slowly for non-chaotic trajectories but rapidly for chaotic trajectories. When the predictions are different, general-relativistic mechanics must therefore be used, instead of special-relativistic mechanics (Newtonian mechanics), to correctly study the dynamics of a weak-gravity system (a low-speed weak-gravity system)

Multi-Centered Black Hole Flows

We describe the systematical construction of the first order formalism for multi-centered black holes with flat three dimensional base-space, within the so-called $T^{3}$ model of N=2, D=4 ungauged Maxwell-Einstein supergravity. The three possible flow classes (BPS, composite non-BPS and almost-BPS) are analyzed in detail, and various solutions, such as single-centered (static or under-rotating) and all known multi-centered black holes, are recovered in this unified framework. We also consider the possibility of obtaining new solutions. The almost-BPS class is proved to split into two general sub-classes, corresponding to a positive or negative value of the duality-invariant polynomial for the total charge; the well known almost BPS system is shown to be a particular solution of the second sub-class.Comment: 17 pages,no figure