In this study, we propose a method for applying a temporal relation identification model to functional requirements. We discuss the limited availability of data in the requirements engineering domain ...compared to other fields when used for supervised learning, and therefore employ a corpus from the news domain for training. The experimental results demonstrate that the types of temporal relations present in functional requirements are limited, indicating that focusing on learning with a narrowed set of labels is effective. Additionally, We incorporate Dependency Path (DP) into the temporal relation identification model and report, through comparative experiments, that leveraging DP is effective, but minor modifications to DP do not lead to significant improvements in accuracy. By demonstrating specific application methods of temporal relation identification in requirements engineering, we anticipate contributing to the analysis of functional requirements in software development.
In software development, ambiguities in requirements described in natural language (NL) prevent the application of formal approaches, posing a difficulty that has heretofore been avoided in two main ...ways: discovery based on formal specifications generated from NL requirements, and the creation of non-ambiguous NL requirements. In the former, NL is more expressive and does not rely on the user's expertise, but instead makes the automatic generation of formal specifications difficult. The latter facilitates the automatic generation of formal specifications and has the advantage of reduced syntactic complexity, but in exchange for reduced expressiveness of NL. In this paper, we take an approach that allows users to describe highly expressive NL requirements and reduces syntactic complexity to support the automatic generation of formal specifications from NL requirements. We also propose an information extraction method using syntactic patterns of low syntactic complexity. Applying our method to practical requirement sentences reveals that it is effective in reducing the complexity of information extraction rules. We expect that our method can support the automatic generation of formal specifications from NL requirements without compromising the expressive power of the language.
Model checking with a time aspect is often used in verification on hardware and embedded systems. Timed automata are often used for such models. UPPAAL is a world-wide famous model checking tool for ...timed automata; however, UPPAAL is a Computational Tree Logic (CTL)-based model checking tool and cannot use Linear Temporal Logic (LTL) properties. Bounded model checking uses LTL (Linear Time Logic) for a checking formula. Bounded model checking specifies a boundary k and obtains counterexamples by searching from the initial state of a system to states reachable by k-steps. There are several studies on bounded model checking. Sorea has proposed a concrete algorithm for a timed automaton. There are, however, no clear details on how to implement bounded model checking tools for timed automata, and study the performance. Another problem is that the timed automaton covered by the method does not support general variables except for clock variables. The objective of this study is to implement a bounded model checking tool using LTL for timed automata. We also improve Sorea's method so that it can handle extended timed automata that handle general variables. This paper also presents some LTL examples from texts on requirement specifications for embedded systems and the results of applying the tool to them.
The chemical control agent 3-(3-indolyl)butanoic acid, previously reported as a control agent for the bacterial wilt pathogen
Ralstonia solanacearum, was shown to suppress the growth of green algae ...during hydroponic culture of tomato. The algicidal activity of the compound was effective at 10
μg/ml, completely preventing generation of green algae under non-shaded greenhouse conditions. The algicidal effect was mainly due to suppression of the growth of motile unicellular algal cells tentatively identified as
Chlamydomonas spp., which are commonly occurring in the hydroponic solution and vigorously multiply to form an algal mat on the sponge supports. The compound has potential as a non-phytotoxic algicide for hydroponically cultured crop plants.
Abstract
Accumulation of tau protein is a key pathology of age-related neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Those diseases are collectively ...termed tauopathies. Tau pathology is associated with axonal degeneration because tau binds to microtubules (MTs), a component of axon and regulates their stability. The acetylation state of MTs contributes to stability and histone deacetylase 6 (HDAC6) is a major regulator of MT acetylation status, suggesting that pharmacological HDAC6 inhibition could improve axonal function and may slow the progression of tauopathy. Here we characterize
N
-(1R,2R)-2-{3-5-(difluoromethyl)-1,3,4-oxadiazol-2-yl-5-oxo-5H,6H,7H-pyrrolo3,4-bpyridin-6-yl}cyclohexyl-2,2,3,3,3-pentafluoropropanamide (T-518), a novel, potent, highly selective HDAC6 inhibitor with clinically favorable pharmacodynamics. T-518 shows potent inhibitory activity against HDAC6 and superior selectivity over other HDACs compared with the known HDAC6 inhibitors in the enzyme and cellular assays. T-518 showed brain penetration in an oral dose and blocked HDAC6-dependent tubulin deacetylation at Lys40 in mouse hippocampus. A 2-week treatment restored impaired axonal transport and novel object recognition in the P301S tau Tg mouse, tauopathy model, while a 3-month treatment also decreased RIPA-insoluble tau accumulation. Pharmaceutical inhibition of HDAC6 is a potential therapeutic strategy for tauopathy, and T-518 is a particularly promising drug candidate.
Many extracellular signals stimulate phosphatidylinositol-3-kinase, which in turn activates the Rac1 GTPase, the protein kinase Akt and the Akt Thr 308 upstream kinase PDK1. Active Rac1 stimulates a ...number of events, including substrate phosphorylation by a subgroup of the PAK family of kinases. The combined effects of Rac1, PDK1 and Akt are crucial for cell migration, growth, survival, metabolism and tumorigenesis. Here we show that Rac1 stimulates a second, kinase-independent function of PAK1. The PAK1 kinase domain serves as a scaffold to facilitate Akt stimulation by PDK1 and to aid recruitment of Akt to the membrane. PAK differentially activates subpopulations of Akt. These findings reveal scaffolding functions of PAK that regulate the efficiency, localization and specificity of the PDK1-Akt pathway.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI‐RADS) has become widespread worldwide, the problem of inter‐observer variability remains. To maintain ...uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI‐RADS3 or lower or BI‐RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep‐learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI‐RADS3 or lower and BI‐RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.
ROC curve by possible thresholds of the confidence score for the detection in each image of BI‐RADS 4A or higher.
Gaucher disease (GD), the most common lysosomal storage disorders, is caused by GBA gene mutations resulting in glycosphingolipids accumulations in various tissues, such as the brain. While ...suppressing glycosphingolipid accumulation is the central strategy for treating peripheral symptoms of GD, there is no effective treatment for the central nervous system symptoms. As glycosphingolipid biosynthesis starts from ceramide glycosylation by glucosylceramide synthase (GCS), inhibiting GCS in the brain is a promising strategy for neurological GD. Herein, we discovered T‐036, a potent and brain‐penetrant GCS inhibitor with a unique chemical structure and binding property. T‐036 does not harbor an aliphatic amine moiety and has a noncompetitive inhibition mode to the substrates, unlike other known inhibitors. T‐036 exhibited sufficient exposure and a significant reduction of glucosylsphingolipids in the plasma and brain of the GD mouse model. Therefore, T‐036 could be a promising lead molecule for treating central nervous system symptoms of GD.
Suppression of glycosphingolipids accumulations by inhibition of glucosylceramide synthase (GCS) is considered a promising therapeutic approach for Gaucher disease. However, there is no effective treatment for the central nervous system symptoms today. Here, we report discovery of a novel GCS inhibitor T‐036, which is potent, orally effective, and brain‐penetrant. T‐036 does not harbor an aliphatic amine moiety and has a non‐competitive, inhibitory binding mode to the substrates unlike other known inhibitors. T‐036 exhibited significant reduction of glycosphingolipids in the disease mouse model. Therefore, T‐036 could be a promising lead molecule for treating central nervous system symptoms of GD.
Abstract
The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer developed evidence-based clinical practice guidelines for the care of psychologically ...distressed bereaved families who have lost members to physical illness including cancer. The guideline development group formulated two clinical questions. A systematic literature review was conducted. The level of evidence and the strength of the recommendations were graded and recommendation statements validated using the modified Delphi method. The recommendations were as follows: non-pharmacological interventions were indicated for serious psychological distress (depression and grief); antidepressants were indicated for depression; however, psychotropic medications including antidepressants were not recommended for ‘complicated’ grief. These guidelines will facilitate the provision of appropriate care to distressed bereaved family members and highlight areas where further research is needed.
The first clinical practice guidelines to optimize care for psychologically distressed bereaved families who have lost a member to physical illness were devised using the formal guideline development method.
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