16 research outputs found

    Metric and Tool Support for Instant Feedback of Source Code Readability

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    In the software maintenance phase, comprehending the legacy source code is inevitable, which consumes most of the time of the phase. The better the code is readable, the easier it is for code readers to comprehend the system based on the source code. This paper proposes an enhanced source code readability metric to quantitatively measure the extent of code readability. In addition, we developed a tool support named Instant R. Gauge to update the code on the fly based on the readability feedback of the current code. The tool also provides the history of the readability change so that developers recognize the more readable code and gradually change their coding habit without any annoying advice. The suggested readability metric achieves 75.74% of explanatory power, and our experiment showed that readability of most of the methods authored in our tool is higher than that of the methods without our approach

    Gut Microbial Metabolites Induce Changes in Circadian Oscillation of Clock Gene Expression in the Mouse Embryonic Fibroblasts

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    Circadian rhythm is an endogenous oscillation of about 24-h period in many physiological processes and behaviors. This daily oscillation is maintained by the molecular clock machinery with transcriptional-translational feedback loops mediated by clock genes including Period2 (Per2) and Bmal1. Recently, it was revealed that gut microbiome exerts a significant impact on the circadian physiology and behavior of its host; however, the mechanism through which it regulates the molecular clock has remained elusive. 3-(4-hydroxyphenyl)propionic acid (4-OH-PPA) and 3-phenylpropionic acid (PPA) are major metabolites exclusively produced by Clostridium sporogenes and may function as unique chemical messengers communicating with its host. In the present study, we examined if two C. sporogenes-derived metabolites can modulate the oscillation of mammalian molecular clock. Interestingly, 4-OH-PPA and PPA increased the amplitude of both PER2 and Bmal1 oscillation in a dosedependent manner following their administration immediately after the nadir or the peak of their rhythm. The phase of PER2 oscillation responded differently depending on the mode of administration of the metabolites. In addition, using an organotypic slice culture ex vivo, treatment with 4-OH-PPA increased the amplitude and lengthened the period of PER2 oscillation in the suprachiasmatic nucleus and other tissues. In summary, two C. sporogenes-derived metabolites are involved in the regulation of circadian oscillation of Per2 and Bmal1 clock genes in the host's peripheral and central clock machineries.1

    A Prognostic Method of Assessing Solder Joint Reliability Based on Digital Signal Characterization

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    Electronics are subjected to thermal, mechanical or chemical stress conditions during their operations. These stress conditions accumulate damages to the electronic system, adversely affecting its components and interconnects including solder joints. Solder joint degradation can cause system malfunctioning, which eventually results in catastrophic failures. In order to prevent system failures, it is required to manage the system health continuously by monitoring damages such as solder joint degradation. Regardless of stress conditions, solder joints often start to degrade from their surface where high speed signals in an electric circuit are concentrated due to the phenomenon referred to as the skin effect. Thus, high speed signals such as digital signals can serve as a sensitive means of detecting solder joint degradation at early stages. This paper presents a diagnosing method of assessing solder joint reliability based on digital signal characterization. Accelerated life tests are conducted to generate solder joint failure. The test setup consists of a circuit board with solder joints, a digital signal transceiver, an environmental test chamber and a stress application fixture. Constant mechanical shear stress is applied to the solder joints of a circuit board at an elevated temperature. A digital signal transceiver generates high speed signals travelling through the solder joints, and continuously monitors the signal characteristics which indicate signal integrity. The test results confirm that the signal characteristics show statistically significant variations between intact and cracked state of the solder joint, and the parameter variations indicate the deterioration of the signal integrity. These results suggest that digital communication signals can be used as a non-destructive diagnostic tool of physical degradation. It can be improved as a tool which provides early warning of impending system failures without installing additional fault sensing instrumen- s. This diagnostic approach may serve as a proactive prognostic module that allows for real-time health management of electronic products and systems

    Encoding and verification of a computer- interpretable guideline: a case study of pressure-ulcer management

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    Abstract This study examined ways to improve the accuracy of translating clinical practice guidelines (CPGs) into a computer-interpretable guideline (CIG) for pressure-ulcer management using the Shareable Active Guideline Environment (SAGE) guideline model, and aimed to verify the accuracy of the obtained CIG. The study was conducted using the following procedures: selecting CPGs, extracting rules from the selected CPGs, developing a CIG using the SAGE guideline model, and verifying the obtained CIG with test cases using an execution engine. The CIG for pressure-ulcer management was developed based on 38 rules and three algorithms at the semiformal representation level using MS Excel and MS Visio. The CIG was encoded by two Activity Graphs consisting of 115 instances representing algorithms and rules as knowledge elements in the SAGE guideline model. Two errors were found and corrected. Results of the study demonstrated that a CIG representing knowledge on pressure-ulcer management can be effectively developed using commonly available programs and the SAGE guideline model, and that the obtained CIG can be verified with a locally developed execution engine. The CIG developed in the study could contribute to health information management once it is implemented successfully in a clinical decision support system

    Transcriptomic Analysis of Polyhexamethyleneguanidine-Induced Lung Injury in Mice after a Long-Term Recovery

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    Polyhexamethyleneguanidine phosphate (PHMG-P) is one of the causative agents of humidifier disinfectant-induced lung injury. Direct exposure of the lungs to PHMG-P causes interstitial pneumonia with fibrosis. Epidemiological studies showed that patients with humidifier disinfectant-associated lung injuries have suffered from restrictive lung function five years after the onset of the lung injuries. We investigated whether lung damage was sustained after repeated exposure to PHMG-P followed by a long-term recovery and evaluated the adverse effects of PHMG-P on mice lungs. Mice were intranasally instilled with 0.3 mg/kg PHMG-P six times at two weeks intervals, followed by a recovery period of 292 days. Histopathological examination of the lungs showed the infiltration of inflammatory cells, the accumulation of extracellular matrix in the lung parenchyma, proteinaceous substances in the alveoli and bronchiolar–alveolar hyperplasia. From RNA-seq, the gene expression levels associated with the inflammatory response, leukocyte chemotaxis and fibrosis were significantly upregulated, whereas genes associated with epithelial/endothelial cells development, angiogenesis and smooth muscle contraction were markedly decreased. These results imply that persistent inflammation and fibrotic changes caused by repeated exposure to PHMG-P led to the downregulation of muscle and vascular development and lung dysfunction. Most importantly, this pathological structural remodeling induced by PHMG-P was not reversed even after long-term recovery

    microRNA-25 as a novel modulator of circadian Period2 gene oscillation

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    Circadian rhythm: microRNAs keep the clock in order A newly identified microRNA plays a key role in fine-tuning the genetic interactions governing the circadian rhythms in mammals, according to researchers in South Korea. Numerous studies have suggested that the Period genes, which negatively regulate the CLOCK and BMAL1 genes to produce a 24-hour feedback loop, may be further modified by microRNAs after they are transcribed. Kyungjin Kim at Daegu Gyeongbuk Institute of Science and Technology, South Korea, and co-workers confirmed that a novel microRNA, miR-25-3p, reduces the expression of a Period gene, Per2, in mice. When miR-25-3p is over-expressed, it dampens and shortens the oscillations of Per2 levels. Interestingly, the researchers showed that natural miR-25-3p expression levels varied across different parts of the brain, supporting the theory that different tissues of the body maintain their own unique circadian cycles

    Mechanical Durability of Flexible Printed Circuit Boards Containing Thin Coverlays Fabricated with Poly(Amide-Imide-Urethane)/Epoxy Interpenetrating Networks

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    Because electronics are becoming flexible, the demand for techniques to manufacture thin flexible printed circuit boards (FPCBs) has increased. Conventional FPCBs are fabricated by attaching a coverlay film (41 μm) onto copper patterns/polyimide (PI) film to produce the structure of coverlay/Cu patterns/PI film. Given that the conventional coverlay consists of two layers of polyimide film and adhesive, its thickness must be reduced to generate thinner FPCBs. In this study, we fabricated 25-μm-thick poly(amide-imide-urethane)/epoxy interpenetrating networks (IPNs) to replace the thick conventional coverlay. Poly(amide-imide-urethane) (PAIU) was synthesized by reacting isocyanate-capped polyurethane with trimellitic anhydride and then mixed with epoxy resin to produce PAIU/epoxy IPNs after curing. Thanks to the soft segments of polyurethane, the elongation of PAIU/epoxy IPNs increased with increasing PAIU content and reached over 200%. After confirming the excellent thermal stability and chemical resistance of the PAIU/epoxy IPNs, we fabricated FPCBs by equipping them as coverlays. The mechanical durability of the FPCBs was evaluated through an MIT folding test, and the FPCB fabricated with PAIU/ep-2 was stable up to 164 folding cycles because of the balanced mechanical properties

    Pharmacological Rescue with SR8278, a Circadian Nuclear Receptor REV-ERB alpha Antagonist as a Therapy for Mood Disorders in Parkinson's Disease

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    Parkinson's disease is a neurodegenerative disease characterized by progressive dopaminergic neuronal loss. Motor deficits experienced by patients with Parkinson's disease are well documented, but non-motor symptoms, including mood disorders associated with circadian disturbances, are also frequent features. One common phenomenon is "sundowning syndrome," which is characterized by the occurrence of neuropsychiatric symptoms at a specific time (dusk), causing severe quality of life challenges. This study aimed to elucidate the underlying mechanisms of sundowning syndrome in Parkinson's disease and their molecular links with the circadian clock. We demonstrated that 6-hydroxydopamine (6-OHDA)-lesioned mice, as Parkinson's disease mouse model, exhibit increased depression- and anxiety-like behaviors only at dawn (the equivalent of dusk in human). Administration of REV-ERB alpha antagonist, SR8278, exerted antidepressant and anxiolytic effects in a circadian time-dependent manner in 6-OHDA-lesioned mice and restored the circadian rhythm of mood-related behaviors. 6-OHDA-lesion altered DAergic-specific Rev-erb alpha and Nurr1 transcription, and atypical binding activities of REV-ERB alpha and NURR1, which are upstream nuclear receptors for the discrete tyrosine hydroxylase promoter region. SR8278 treatment restored the binding activities of REV-ERB alpha and NURR1 to the tyrosine hydroxylase promoter and the induction of enrichment of the R/N motif, recognized by REV-ERB alpha and NURR1, as revealed by ATAC-sequencing; therefore, tyrosine hydroxylase expression was elevated in the ventral tegmental area of 6-OHDA-injected mice, especially at dawn. These results indicate that REV-ERB alpha is a potential therapeutic target, and its antagonist, SR8278, is a potential drug for mood disorders related to circadian disturbances, namely sundowning syndrome, in Parkinson's disease
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