Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

An automated tool for semantic accessing to formal software models

Many software engineers have found that it is difficult to understand, incorporate and use different formal models consistently in the process of software developments, especially for large and complex software systems. This is mainly due to the complex mathematical nature of the formal methods and the lack of tool support. It is highly desirable to have software models and their related software artefacts systematically connected and used collaboratively, rather than in isolation. The success of the Semantic Web, as the next generation of Web technology, can have profound impact on the environment for formal software development. It allows both the software engineers and machines to understand the content of formal models and supports more effective software design in terms of understanding, sharing and reusing in a distributed manner. To realise the full potential of the Semantic Web in formal software development, effectively creating proper semantic metadata for formal software models and their related software artefacts is crucial. This paper proposed a framework that allows users to interconnect the knowledge about formal software models and other related documents using the semantic technology. We first propose a methodology with tool support is proposed to automatically derive ontological metadata from formal software models and semantically describe them. We then develop a Semantic Web environment for representing and sharing formal Z/OZ models. A method with prototype tool is presented to enhance semantic query to software models and other artefacts. © 2014.

A Log Tool for Software Systems Analyses

The article presents a new type of logs merging tool for multiple blade telecommunication systems based on the development of a new approach. The introduction of the new logs merging tool (the Log Merger) can help engineers to build a processes behavior timeline with a flexible system of information structuring used to assess the changes in the analyzed system. This logs merging system based on the experts experience and their analytical skills generates a knowledge base which could be advantageous in further decision-making expert system development. This paper proposes and discusses the design and implementation of the Log Merger, its architecture, multi-board analysis of capability and application areas. The paper also presents possible ways of further tool improvement e.g. - to extend its functionality and cover additional system platforms. The possibility to add an analysis module for further expert system development is also considered.

The application of uncertainty evaluating software for the utilisation of machine tool systems for final inspection

As machine tools continue to become increasingly repeatable and accurate, high-precision manufacturers may be tempted to consider how they might utilise machine tools as measurement systems. In this paper, we have explored this paradigm by attempting to repurpose state-of-the-art coordinate measuring machine Uncertainty Evaluating Software (UES) for a machine tool application. We performed live measurements on all the systems in question. Our findings have highlighted some gaps with UES when applied to machine tools, and we have attempted to identify the sources of variation which have led to discrepancies. Implications of this research include requirements to evolve the algorithms within the UES if it is to be adapted for on-machine measurement, improve the robustness of the input parameters, and most importantly, clarify expectations.

An integrated framework for ensuring the quality of software design

Software development is an extremely complex process, during which human errors are introduced and result in faulty software systems. It is highly desirable and important that these errors can be prevented and detected as early as possible. Software architecture design is a high-level system description, which embodies many system features and properties that are eventually implemented in the final operational system. Therefore, methods for modeling and analyzing software architecture descriptions can help prevent and reveal human errors and thus improve software quality. Furthermore, if an analyzed software architecture description can be used to derive a partial software implementation, especially when the derivation can be automated, significant benefits can be gained with regard to both the system quality and productivity. This dissertation proposes a framework for an integrated analysis on both of the design and implementation. To ensure the desirable properties of the architecture model, we apply formal verification by using the model checking technique. To ensure the desirable properties of the implementation, we develop a methodology and the associated tool to translate an architecture specification into an implementation written in the combination of Arch-Java/Java/AspectJ programming languages. The translation is semi-automatic so that many manual programming errors can be prevented. Furthermore, the translation inserting monitoring code into the implementation such that runtime verification can be performed, this provides additional assurance for the quality of the implementation. Moreover, validations for the translations from architecture model to program are provided. Finally, several case studies are experimented and presented.

A software tool that generates symbolic model verifier (SMV) input language from a predicate transition net

The purpose of this research was to apply model checking by using a symbolic model checker on Predicate Transition Nets (PrT Nets). A PrT Net is a formal model of information flow which allows system properties to be modeled and analyzed. The aim of this thesis was to use the modeling and analysis power of PrT nets to provide a mechanism for the system model to be verified. Symbolic Model Verifier (SMV) was the model checker chosen in this thesis, and in order to verify the PrT net model of a system, it was translated to SMV input language. A software tool was implemented which translates the PrT Net into SMV language, hence enabling the process of model checking. The system includes two parts: the PrT net editor where the representation of a system can be edited, and the translator which converts the PrT net into an SMV program.

Development and validation of an attitudinal-profiling tool for patients with asthma

Peer reviewed

STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail Adults with Limited Life Expectancy): Consensus Validation

Background: To validate STOPPFrail, a list of explicit criteria for potentially inappropriate medications (PIMs) in frailer older adults with limited life expectancy. A Delphi consensus survey of an expert panel (n = 17) comprising specialists in geriatric medicine, clinical pharmacology, palliative care, psychiatry of old age, clinical pharmacy and general practice.
Methods: STOPPFrail criteria was initially created by the authors based on clinical
experience and appraisal of the available literature. Criteria were organised according to physiological system. Each criterion was accompanied by an explanation. Panellists ranked their agreement with each criterion on a 5-point Likert scale and invited to provide written feedback. Criteria with a median Likert response of 4/5 (agree/strongly agree) and a 25th centile of ≥4 were included in the final criteria.
Results: Three Delphi rounds were required. All panellists completed all rounds. Thirty criteria were proposed for inclusion; 26 were accepted. No new criteria were added. The first two criteria suggest deprescribing medications with no indication or where compliance is poor. The remaining 24 criteria include lipid-lowering therapies, alpha-blockers for hypertension, anti-platelets, neuroleptics, proton pump inhibitors, H-2 receptor antagonists, anti-spasmodics, theophylline, leukotriene antagonists, calcium supplements, bone anti-resorptive therapy, selective oestrogen receptor modulators, non-steroidal antiinflammatories, corticosteroids, 5-alpha reductase inhibitors, alpha-1 selective blockers, muscarinic antagonists, oral diabetic agents, ACE-inhibitors, angiotensin receptor blockers, systemic oestrogens, multivitamins, nutritional supplements and prophylactic antibiotics. Anticoagulants and anti-depressants were excluded. Despite incorporation of panellists’ suggestions, memantine and acetyl-cholinesterase inhibitors remained inconclusive.
Conclusion: STOPPFrail comprises 26 criteria, which have been judged by broad consensus, to be potentially inappropriate in frailer older patients with limited life expectancy. STOPPFrail may assist in deprescribing medications in these patients.

DORIS Software. New Tool to Process Sound Velocity Profiles

Hydrographic and geosciences surveys, using acoustic devices, need to use accurate water sound velocity profiles. Because the acoustic path depends on the sound velocity profile (SVP), the use of the most accurate SVP is one of the keys to conducting effective surveys (with multibeams, for instance). To date, the existing software available does not answer to both the needs of efficiency and simplicity (sometimes not so easy to operate, sometimes not so accurate). DORIS provides a handy freeware to post-process SVP for the hydrographic communities.

XML-Intensive software development

168 p.

Psychometric properties of the Iranian version of the premature ejaculation diagnostic tool

Introduction Premature ejaculation (PE) is one of the most prevalent male sexual problems. The Premature Ejaculation Diagnostic Tool (PEDT) is a suitable patient-reported outcome measure for the assessment of PE. Aim To examine the psychometric proporties of a translated and culturally adapted version of the PEDT in a sample of Iranian men suffering from PE. Methods Two independent samples were compared, one including patients with PE based on the DSM-IV-TR criteria (n = 269) and the other including healthy men without PE (n = 289). A backward–forward translation procedure was used to translate the PEDT into Persian. Both samples were asked to fill in the PEDT twice—at baseline and 4 weeks later. Main Outcome Measures Internal consistency, test–retest reliability, convergent validity, factor structure, measurement invariance across sexual health status (i.e., between men with and without PE). Results Mean ages of men without and with PE were 34.9 and 35.3 years, respectively. Cronbach's alpha coefficient for the total PEDT score was 0.89. All items and the total score were remarkably consistent between the two measurement points. All five PEDT items correlated at r = 0.40 or greater with their own scale, indicating good convergent validity. There was a high and significant correlation (r = −0.82, P  < 0.001) between the PEDT score and IELT. Healthy men reported lower scores (fewer complaints) on the PEDT compared with the PE group. A single-factor model was found to be best-fitting in the exploratory factor analysis; this was confirmed by confirmatory factor analysis. The PEDT was invariant across sexual health status and perceived similarly by men with and without PE. Conclusion The results provide evidence for good reliability and validity of the Iranian version of the PEDT. The questionnaire therefore represents a suitable tool for screening PE in Iranian men.

Moral reasoning in sport: validation of the Portuguese version of the RSBH value-judgement inventory in adolescents

The purpose of this study was to examine the validity and reliability of the Portuguese version of the Rudd Stoll Beller Hahm Value-judgement Inventory (RSBHVI) in a sample of adolescents. The RSBHVI, which measures moral and social reasoning, was translated using a back translation method. A sample of 238 10th to 12th grade high school students (age mean value 16.93 years, s = 1.34) completed the Portuguese versions of RSBH, and the Task and Ego-orientation Questionnaire. Partial support for the original structure of the moral reasoning scale, but not the social reasoning scale, was found. Females, and non-athletes and individual sport athletes scored significantly higher than males and team sport athletes in moral reasoning, respectively. Moral reasoning was negatively correlated with ego-orientation (r = −30; p <. 001) and uncorrelated with task-orientation (r = .10, p > .05). Participants who were low-ego scored higher in moral reasoning than those who were high-ego. It is suggested that decreasing levels of ego-orientation may be necessary to improve athletes’ moral reasoning.

Validación del software educativo Poliestudio 1.0: informe de investigación

PoliEstudio 1.0 is a computational tool, with free license, created to work with polynomial expressions in one variable and it was created by a team in which the authors of this article are part of. This article documents the qualitative validation performed to this software which main objective was to bring to the Costa Rican Educational System a validated educational software that can solve, partially, the problems that nowadays exists in the mathematic education of secondary students, particularly in the topics related to polynomial expressions in one variable and specifically to those students who are in eighth grade.