1,018 research outputs found
Automatic Generation of Test Cases based on Bug Reports: a Feasibility Study with Large Language Models
Software testing is a core discipline in software engineering where a large
array of research results has been produced, notably in the area of automatic
test generation. Because existing approaches produce test cases that either can
be qualified as simple (e.g. unit tests) or that require precise
specifications, most testing procedures still rely on test cases written by
humans to form test suites. Such test suites, however, are incomplete: they
only cover parts of the project or they are produced after the bug is fixed.
Yet, several research challenges, such as automatic program repair, and
practitioner processes, build on the assumption that available test suites are
sufficient. There is thus a need to break existing barriers in automatic test
case generation. While prior work largely focused on random unit testing
inputs, we propose to consider generating test cases that realistically
represent complex user execution scenarios, which reveal buggy behaviour. Such
scenarios are informally described in bug reports, which should therefore be
considered as natural inputs for specifying bug-triggering test cases. In this
work, we investigate the feasibility of performing this generation by
leveraging large language models (LLMs) and using bug reports as inputs. Our
experiments include the use of ChatGPT, as an online service, as well as
CodeGPT, a code-related pre-trained LLM that was fine-tuned for our task.
Overall, we experimentally show that bug reports associated to up to 50% of
Defects4J bugs can prompt ChatGPT to generate an executable test case. We show
that even new bug reports can indeed be used as input for generating executable
test cases. Finally, we report experimental results which confirm that
LLM-generated test cases are immediately useful in software engineering tasks
such as fault localization as well as patch validation in automated program
repair
Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin
Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1
Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms
Streptococcus pneumoniae (the 'pneumococcus') is a significant cause of morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteraemia, and meningitis, with an annual death burden of over one million. Discovered over a century ago, pneumococcal serotype 1 (S1) is a significant cause of these life-threatening diseases. Our understanding of the epidemiology and biology of pneumococcal S1 has significantly improved over the past two decades, informing the development of preventative and surveillance strategies. However, many questions remain unanswered. Here, we review the current state of knowledge of pneumococcal S1, with a special emphasis on clinical epidemiology, genomics, and disease mechanisms
Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease.
The CABLES1 cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell line (AtT20/D16v-F2). The four patients had macroadenomas. We provide evidence for a role of CABLES1 as a novel pituitary tumor-predisposing gene. Its function might link two of the main molecular mechanisms altered in corticotropinomas: the cyclin-dependent kinase/cyclin group of cell cycle regulators and the epidermal growth factor receptor signaling pathway. Further studies are needed to assess the prevalence of CABLES1 mutations among patients with other types of pituitary adenomas and to elucidate the pituitary-specific functions of this gene
New Mathematical approaches in Electrocardiography Imaging inverse problem
International audienceImprove ECGI inverse problem reconstruction Introduce new mathematical approches to the field of the ECGI inverse problem Compare the performance of the new mathematical approaches to the state-of-the-art methods, mainly the MFS method used in commercial devices. In silico validation of the new approches. Assessment of some simplification hypothesis: Torso inhomogeneity Propose some uncertainty quantification apronches to deal with measurements errors Context and objectives Optimal control approach Mathematical model In silico gold standard Results Torso Heterogeneity effect Conclusions Forward model If we know the heart potential we can compute the electrical potential Inverse problem If we know the electrical potential and the current density at the outer boundary of the torso and we look for the electrical potential at the heart surface Computational heart and torso anatomical models + electrodes position Computational torso meshes: 250 nodes mesh (blue). More accurate FE mesh with 6400 nodes (green) Remarks Introducing the torso heterogeneity is natural with FEM. also anisotropy could be introduced The error is more important in the left ventricle Main results and perspectives New mathematical approches for solving the inverse problem in electrocardiography imaging based on optimal control Over all the 20 cases used in this study the optimal control method performs better than the MFS both in terms of relative error and correlation coefficient: Acknowledgment: This work was partially supported by an ANR grant part of "Investissements d'Avenir" program with reference ANR-10-IAHU-04. It is also supported by the LIRIMA international lab thought the EPICARD tea
Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report
BACKGROUND: Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein. CASE PRESENTATION: A 36-year-old immunocompetent woman presented with acute primary cytomegalovirus infection in association with extensive thrombosis in the portal and splenic vein. In addition, a fresh thrombus was evident in the right hepatic vein. A thorough evaluation for a hypercoagulable state was negative. The clinical course, biological evolution, radiological and histological findings were consistent with cytomegalovirus hepatitis complicated by a partial acute Budd-Chiari syndrome and portal thrombosis. Therapeutic anticoagulation was associated with a slow clinical improvement and partial vascular recanalization. CONCLUSION: We described in details a new association between cytomegalovirus infection and acute venous thrombosis both in the portal vein and in the right hepatic vein, realizing a partial Budd-Chiari syndrome. One should be aware that this rare thrombotic event may be complicated by partial venous outflow block
Arthropod Distribution In A Tropical Rainforest: Tackling A Four Dimensional Puzzle
Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods.1012SolVin-Solvay SASTRIUnited Nations Environment ProgrammeSmithsonian Institution (Walcott Fund)European Science FoundationGlobal Canopy ProgrammeCzech Science foundation GACR grant [14-36098G]European Social FundCzech Ministry of Education [CZ.1.07/2.3.00/20.0064]U.S. National Science Fundation [DEB-0841885]Australian Research Council [FT100100040]Conselho Nacional de Desenvolvimento CientĂfico e TecnolĂłgico (CNPq)"Investissement d'Avenir'' grant [ANR-10-LABX-25-01]Norwegian Research CouncilGrant Agency of the Czech Republic [14-36098G
Review of the Amphibian Immune Response to Chytridiomycosis, and Future Directions
The fungal skin disease, chytridiomycosis (caused by Batrachochytrium dendrobatidis and B. salamandrivorans), has caused amphibian declines and extinctions globally since its emergence. Characterizing the host immune response to chytridiomycosis has been a focus of study with the aim of disease mitigation. However, many aspects of the innate and adaptive arms of this response are still poorly understood, likely due to the wide range of species' responses to infection. In this paper we provide an overview of expected immunological responses (with inference based on amphibian and mammalian immunology), together with a synthesis of current knowledge about these responses for the amphibian-chytridiomycosis system. We structure our review around four key immune stages: (1) the naĂŻve immunocompetent state, (2) immune defenses that are always present (constitutive defenses), (3) mechanisms for recognition of a pathogen threat and innate immune defenses, and (4) adaptive immune responses. We also evaluate the current hot topics of immunosuppression and immunopathology in chytridiomycosis, and discuss their respective roles in pathogenesis. Our synthesis reveals that susceptibility to chytridiomycosis is likely to be multifactorial. Susceptible amphibians appear to have ineffective constitutive and innate defenses, and a late-stage response characterized by immunopathology and Bd-induced suppression of lymphocyte responses. Overall, we identify substantial gaps in current knowledge, particularly concerning the entire innate immune response (mechanisms of initial pathogen detection and possible immunoevasion by Bd, degree of activation and efficacy of the innate immune response, the unexpected absence of innate leukocyte infiltration, and the cause and role of late-stage immunopathology in pathogenesis). There are also gaps concerning most of the adaptive immune system (the relative importance of B and T cell responses for pathogen clearance, the capacity and extent of immunological memory, and specific mechanisms of pathogen-induced immunosuppression). Improving our capacity for amphibian immunological research will require selection of an appropriate Bd-susceptible model species, the development of taxon-specific affinity reagents and cell lines for functional assays, and the application of a suite of conventional and emerging immunological methods. Despite current knowledge gaps, immunological research remains a promising avenue for amphibian conservation management
Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers
Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates.
Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS.
Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS.
Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management
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