Mature software systems comprise a vast number of heterogeneous system capabilities which are usually requested by different groups of stakeholders and which evolve over time. Software features ...describe and bundle low level capabilities logically on an abstract level and thus provide a structured and comprehensive overview of the entire capabilities of a software system. Software features are often not explicitly managed. Quite the contrary, feature-relevant information is often spread across several software engineering artifacts (e.g., user manual, issue tracking systems). It requires huge manual effort to identify and extract feature-relevant information from these artifacts in order to make feature knowledge explicit. In this paper we present a two-step-approach to extract feature-relevant information from a user manual: First we semi-automatically extract a domain terminology from a natural language user manual based on linguistic patterns. Then, we apply natural language processing techniques based on the extracted domain terminology and structural sentence information. Our approach is able to extract atomic feature-relevant information with an F
1
-score of at least 92.00%. We describe the implementation of the approach as well as evaluations based on example sections of a user manual taken from industry.
The Common Component Architecture (CCA) provides a means for software developers to
manage the complexity of large-scale scientific simulations and to move toward a
plug-and-play environment for ...high-performance coputing. In the scientific
computing context, component models also promote collaboration using independently
developed software, thereby allowing particular individals or groups to focus on the
aspects of greatest interest to them. The CCA supports parallel and distributed
coputing as well as local high-performance connections between components in a
language-independent manner. The design places minimal requirements on components
and thus facilitates the integration of existing code into the CCA environment. The
CCA model imposes minimal ovehead to minimize the impact on application performance.
The focus on high performance distinguishes the CCA from most other component
models. The CCA is being applied within an increasing range of disciplines,
including cobustion research, global climate simulation, and computtional chemistry.
Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during ...inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r = 0.785 P < 0.001; chronic inflammation after anti-TNF: r = 0.558 P < 0.001), IL-8 (Sepsis: r = 0.714 P<0.004; healthy controls after exercise r = 0.786 P < 0.028; chronic inflammation before anti-TNF: r = 0.429 P < 0.041) and IL-10 (healthy controls before exercise: r = 0.791 P < 0.028) than with kidney injury or function. Correlation to kidney injury or function was found only in septic patients (for creatinine: r = 0.906 P < 0.001; for eGFR: r = -0.686 P = 0.005) and in patients with rheumatic disease after anti-TNF therapy (for creatinine: r = 0.466 P < 0.025). In stimulation assays with IL-6 and lipopolysaccharide plasma-NGAL was increased. Co-stimulation of lipopolysaccharide with plasma-NGAL decreased cellular injury (P < 0.05) and in trend IL-10 levels (P = 0.057). Septic mice demonstrated a significantly improved survival rate after NGAL treatment (P < 0.01). Plasma-NGAL seams to be strongly involved in inflammation. For clinical relevance, it might not only be useful for AKI detection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential.
NOTCH signaling is deregulated in the majority of T-cell acute lymphoblastic leukemias (T-ALL) as a result of activating mutations in NOTCH1. Gamma secretase inhibitors (GSI) block proteolytic ...activation of NOTCH receptors and may provide a targeted therapy for T-ALL. We have investigated the mechanisms of GSI sensitivity across a panel of T-ALL cell lines, yielding an approach for patient stratification based on pathway activity and also providing a rational combination strategy for enhanced response to GSI. Whereas the NOTCH1 mutation status does not serve as a predictor of GSI sensitivity, a gene expression signature of NOTCH pathway activity does correlate with response, and may be useful in the selection of patients more likely to respond to GSI. Furthermore, inhibition of the NOTCH pathway activity signature correlates with the induction of the cyclin-dependent kinase inhibitors CDKN2D (p19(INK4d)) and CDKN1B (p27(Kip1)), leading to derepression of RB and subsequent exit from the cell cycle. Consistent with this evidence of cell cycle exit, short-term exposure of GSI resulted in sustained molecular and phenotypic effects after withdrawal of the compound. Combination treatment with GSI and a small molecule inhibitor of CDK4 produced synergistic growth inhibition, providing evidence that GSI engagement of the CDK4/RB pathway is an important mechanism of GSI action and supports further investigation of this combination for improved efficacy in treating T-ALL.
X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the ...OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. 'LIAVA', 'LVAVA') with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the 'LIAVA' haplotype derived from an ancestral less deleterious 'LIAVS' haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.
Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 ...independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.
The nuclear dependence of the inclusive inelastic electron scattering cross section (the EMC effect) has been measured for the first time in 10B and 11B. Previous measurements of the EMC effect in A ...≤ 12 nuclei showed an unexpected nuclear dependence; 10B and 11B were measured to explore the EMC effect in this region in more detail. Results are presented for 9Be, 10B, 11B, and 12C at an incident beam energy of 10.6 GeV. The EMC effect in the boron isotopes was found to be similar to that for 9Be and 12C, yielding almost no nuclear dependence in the EMC effect in the range A = 4-12. This represents important, new data supporting the hypothesis that the the EMC effect depends primarily on the local nuclear density due to the cluster structure of these nuclei.
According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected ...by tuberculosis, the emergence of Mycobacterium tuberculosis drug‐resistance is complicating tuberculosis control in many high‐burden countries. During the past 5 years, the global number of patients identified with multidrug‐resistant tuberculosis (MDR‐TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR‐TB. The management of MDR‐TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug‐resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor‐made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR‐TB. The challenge now is to bring these adances to those patients that need them most.
Content List ‐ Read more articles from the symposium: “The 10th International Conference on the Pathogenesis of Mycobacterial Infections”.
Comparing oncological outcomes and toxicity after primary treatment of localized prostate cancer using HDR- or LDR-mono-brachytherapy (BT), or conventionally (CF) or moderately hypofractionated (HF) ...external beam radiotherapy.
Retrospectively, patients with low- (LR) or favorable intermediate-risk (IR) prostate cancer treated between 03/2000 and 09/2022 in two centers were included. Treatment was performed using either CF with total doses between 74 and 78 Gy, HF with 2.4-2.6 Gy per fraction in 30 fractions, or LDR- or HDR-BT. Biochemical control (BC) according to the Phoenix criteria, and late gastrointestinal (GI), and genitourinary (GU) toxicity according to RTOG/EORTC criteria were assessed.
We identified 1293 patients, 697 with LR and 596 with IR prostate cancer. Of these, 470, 182, 480, and 161 were treated with CF, HF, LDR-BT, and HDR-BT, respectively. For BC, we did not find a significant difference between treatments in LR and IR (p = 0.31 and 0.72). The 5‑year BC for LR was between 93 and 95% for all treatment types. For IR, BC was between 88% in the CF and 94% in the HF group. For CF and HF, maximum GI and GU toxicity grade ≥ 2 was between 22 and 27%. For LDR-BT, we observed 67% grade ≥ 2 GU toxicity. Maximum GI grade ≥ 2 toxicity was 9%. For HDR-BT, we observed 1% GI grade ≥ 2 toxicity and 19% GU grade ≥ 2 toxicity.
All types of therapy were effective and well received. HDR-BT caused the least late toxicities, especially GI.
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