Filling the gaps of development logs and bug issue data

It has been suggested that the data from bug repositories is not always in sync or complete compared to the logs detailing the actions of developers on source code. In this paper, we trace two sources of information relative to software bugs: the change logs of the actions of developers and the issues reported as bugs. The aim is to identify and quantify the discrepancies between the two sources in recording and storing the developer logs relative to bugs. Focussing on the databases produced by two mining software repository tools, CVSAnalY and Bicho, we use part of the SZZ algorithm to identify bugs and to compare how the"defects-fixing changes" are recorded in the two databases. We use a working example to show how to do so. The results indicate that there is a significant amount of information, not in sync when tracing bugs in the two databases. We, therefore, propose an automatic approach to re-align the two databases, so that the collected information is mirrored and in sync.Dr. Felipe Orteg

Estrogen Receptor (ER) Alpha Regulatory Mechanisms and Therapeutic Strategies in ER+ Breast Cancer

Breast cancer is among the most frequently diagnosed cancers in the U.S. and is one of the leading causes of cancer-related mortalities, second to lung cancer. Estrogen receptor alpha-positive (ER+) breast cancer accounts for 2/3 of diagnosed cases. Patients diagnosed with this subtype of breast cancer typically undergo endocrine therapy that aims to mitigate the growth-promoting effects of estrogen/ER. While therapies are effective, 1/3 of patients will experience recurrence. To begin addressing this drug-resistant patient population, we investigated potential drug targets involved in response to treatment. Coregulators have been implicated in the regulation of ER transcriptional activity and subsequently affecting the success of treatment with endocrine therapies. Using the mutant biotin ligase labeling system TurboID, we profiled the ER interactome in response to estrogen to identify novel regulators of ER activity. By identifying novel targets, we aim to identify new therapeutically targetable vulnerabilities. Upon cancer recurrence with endocrine therapies, patients are often switched to an alternative endocrine therapy combined with another targeted therapeutic such as a phosphatidylinositol 3,4,5-trisphosphate (PI3K) inhibitor. To further address the potential mechanisms of resistance to targeted therapies such as PI3K inhibitors, we have generated resistance models under various genetic mutations (PIK3CA and PTEN) in the setting of fulvestrant resistance to ascertain kinases that could potentiate tumor survival. Phosphoproteomic analysis of PTEN deficient tumors resistant to PI3K inhibition identified ATM as a top kinase for further validation as to its role in the development of PI3K resistance. For clinical relevance we are also investigating PIK3CA mutants to determine if results observed from phosphoproteomic analyses in a PTEN-deficient model could be extended to models with other forms of PI3K pathway activation and resistance to other subtypes of PI3K inhibitors. Preliminary work has identified that PI3KCA mutant cell lines resistant to both fulvestrant and GDC-0941 show increased sensitivity to ATM inhibition. These findings promote further investigation as to ATM inhibition’s effects on PTEN deficient lines

Contribución al conocimiento de la vegetación de las montañas marroquíes

Different types of plant communities, till now undetected in Morocco, are here described using the phytosociological method. The following new subassociations and associations are proposed: Anthyllido polycephalae-Stachydetum fontqueri subass. quercetosum rotundifoliae is a machia from the Northern Rif Mountains; Genisto anglicae-Ericetum ciliaris subsass. pinguiculetosum lusitanicae is a heathland from the Bou Hassim range in the Western Rif; Cephalario maroccanae-Inuletum maletii is a megaphorbic community from the Middle Atlas; Bellis caerulescendis-Heracletum sphondyllii is a megaphorbic community from the High Atlas; Arenario armerinae-Sideritetum matris-fillae is a high mountain grassland from the Tichchoukt range in the Middle Atlas. New data are given for the syntaxa already described but with the distribution, variability and ecology not well known. This is the case of the following associations: Polysticho setiferi-Prunetum lusitanicae, a riverine woodland from the W Rif Mountains; Primulo acaulis-Betuletum celtibericae, a birch woodland from the C Rif and Astragaletum numidico-maroccani a high mediterranean mountain plant community from the Western Rif. As a conclusion, the vegetation of the peculiar habitats that occur in reduced areas is only partially known.Se describe con la metodología fitosociológica diferentes tipos de comunidades vegetales, no detectadas hasta el presente en Marruecos. Se proponen las siguientes nuevas asociaciones y subasociaciones: Anthyllido polycephalae-Stachydetum fontqueri subass. quercetosum rotundifoliae corresponde a una maquia de las montañas septentrionales del Rif; Genisto anglicae-Ericetum ciliaris subsass. pinguiculetosum lusitanicae es un brezal del macizo de Bou Hassim en el Rif occidental; Cephalario maroccanae- Inuletum maletii es una formación de megaforbios del Atlas Medio; Bellis caerulescendis-Heracletum sphondyllii es una formación de megaforbios del Gran Atlas; Arenario armerinae-Sideritetum matris-filiae es un pastizal de alta montaña mediterránea del macizo de Tichchoukt en el Atlas Medio. Se aportan nuevos datos para otros sintáxones ya descritos pero con la distribución, variabilidad y ecología poco conocidas. Este es el caso de las asociaciones siguientes: Polysticho setiferi-Prunetum lusitanicae, bosquecillo ripario de las montañas del Rif occidental y central; Primulo acaulis-Betuletum celtibericae, corresponde a un bosque de abedules del Rif central, y Astragaletum numidico-maroccani es una comunidad de caméfitos de alta montaña mediterránea conocida hasta el presente del Rif occidental. Como conclusión se puede aseverar que la vegetación de los hábitats que ocupan áreas reducidas en las montañas marroquíes es conocida de forma parcial

Targeting therapeutic vulnerabilities associated with EWS fusion proteins in Ewing sarcoma

Ewing sarcoma (ES) is a are and aggressive bone tumour affecting children and young adults and that requires better therapeutic options to improve patient outcomes. ES is characterised by chromosomal rearrangements producing a fusion gene, the most predominant occurring between EWSR1 and FLI1 (85%). Recent evidence shows that the chimeric oncoprotein EWS-FLI recruits chromatin remodellers that epigenetically rewire transcription to establish its oncogenic programme. Additionally, transcriptional dysregulation is known to induce replication stress (RS) and genomic instability. To mitigate potential genotoxic damage, ES cells are particularly dependent on the replication stress response (RSR). Based on these EWS-FLI1-specific molecular effects, this thesis investigates two separate therapeutic strategies: (i) inhibition of the epigenetic modifier KDM1A, and (ii) exploiting the dependency on the RSR. Catalytic inhibition of histone demethylase KDM1A is demonstrated to be insufficient as a therapeutic strategy for ES, although roles beyond its demethylase function remain a possibility. To identify therapeutic combinations targeting the dependency on the RSR, clinically available drugs inhibiting the ATR-CHK1-WEE1 axis were tested in 3D spheroids of ES cell lines. Each drug candidate was combined at clinically relevant doses with SN-38, the active metabolite of topoisomerase I inhibitor irinotecan, currently used to treat relapsed ES. Combinations revealed cytotoxicity and decreased growth in ES spheroids following WEE1 and ATR inhibition, both concurrent with SN-38. Based on the strength of responses, further investigations prioritised the effects of the WEE1 inhibitor AZD1775 combined with SN-38 in additional ES cell lines and a model ectopically expressing EWS-FLI1. DNA damage, apoptosis, and cell cycle analysis uncovered two responses in ES cell lines, one characterised by cell death, the other resembling growth arrest. These may be dependent on the cell lines' mutational background and could act as a predictive biomarker. Taken together these findings identify a promising novel therapeutic strategy for ES

Survey of quantitative antimicrobial consumption per production stage in farrow-to-finish pig farms in Spain

Objectives: To characterise antimicrobial use (AMU) per production stage in terms of drugs, routes of application, indications, duration and exposed animals in farrow-to-finish pig farms in Spain. Design: Survey using a questionnaire on AMU during the six months prior to the interview, administered in face-to-face interviews completed from April to October 2010. Participants: 108 potentially eligible farms covering all the country were selected using a multistage sampling methodology; of these, 33 were excluded because they did not fulfil the participation criteria and 49 were surveyed. Results: The rank of the most used antimicrobials per farm and production stage and administration route started with polymyxins (colistin) by feed during the growing and the preweaning phases, followed by β-lactams by feed during the growing and the preweaning phases and by injection during the preweaning phase. Conclusions: The study demonstrates that the growing stage (from weaning to the start of finishing) has the highest AMU according to different quantitative indicators (number of records, number of antimicrobials used, percentage of farms reporting use, relative number of exposed animals per farm and duration of exposure); feed is the administration route that produces the highest antimicrobial exposure based on the higher number of exposed animals and the longer duration of treatment; and there are large differences in AMU among individual pig farms

Transient tunneling effects of resonance doublets in triple barrier systems

Transient tunneling effects in triple barrier systems are investigated by considering a time-dependent solution to the Schr\"{o}dinger equation with a cutoff wave initial condition. We derive a two-level formula for incidence energies $E$ near the first resonance doublet of the system. Based on that expression we find that the probability density along the internal region of the potential, is governed by three oscillation frequencies: one of them refers to the well known Bohr frequency, given in terms of the first and second resonance energies of the doublet, and the two others, represent a coupling with the incidence energy $E$. This allows to manipulate the above frequencies to control the tunneling transient behavior of the probability density in the short-time regim