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The maintenance strategies of weapon systems have evolved from corrective maintenance post-failure to time-based preventive maintenance, driven by the growing adoption of diagnostic technologies and data utilization. Currently, there is a transition to Condition-Based Maintenance (CBM) and, where applicable, Condition-Based Maintenance Plus (CBM+). This study investigated the feasibility of applying CBM+ technology using sensor data from weapon systems and explored methods for implementing the related foundational elements. First, the feasibility of CBM+ technology was confirmed by integrating data collection devices into the engine components of selected weapon systems, enabling sensor data collection and monitoring. Second, empirical evidence was gathered on the foundational elements necessary for the broader adoption of CBM+ technology. Practical application methods were proposed based on this evidence, including criteria for implementing CBM+ technology in major operational weapon systems, estimation of sensor data capacity, network methods for data transmission and collection, and the standardization of sensor data. The study’s findings are expected to provide reference points for selecting target weapon systems for the development and application of CBM+ technology, as well as outline essential foundational elements, such as security, networking, and data standardization, critical for leveraging related technologies.

Abstract Background Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment. Results Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event. Conclusion Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy. Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691

The prefrontal cortex (PFC) is a key neural node mediating behavioral responses to stress and the actions of ketamine, a fast-acting antidepressant. The molecular mechanisms underlying these processes, however, are not fully understood. Our recent study revealed a pivotal role of hippocampal Ahnak as a regulator of cellular and behavioral adaptations to chronic stress. However, despite its significant expression in the PFC, the contribution of cortical Ahnak to behavioral responses to stress and antidepressants remains unknown. Here, using a mouse model for chronic social stress, we find that Ahnak expression in the PFC is significantly increased in stress-resilient mice and positively correlated with social interaction after stress exposure. Conditional deletion of Ahnak in the PFC or forebrain glutamatergic neurons facilitates stress susceptibility, suggesting that Ahnak is required for behavioral resilience. Further supporting this notion, Ahnak expression in the PFC is increased after the administration of ketamine or its metabolite (2R, 6R)-hydroxynorketamine (HNK). Moreover, Ahnak deletion in forebrain glutamatergic neurons blocks the restorative behavioral effects of ketamine or HNK in stress-susceptible mice. This forebrain excitatory neuron-specific Ahnak deletion reduces the frequency of mini excitatory postsynaptic currents in layer II/III pyramidal neurons, suggesting that Ahnak may induce its behavioral effects via modulation of glutamatergic transmission in the PFC. Altogether, these data suggest that Ahnak in glutamatergic PFC neurons may be critical for behavioral resilience and antidepressant actions of ketamine or HNK in chronic social stress-exposed mice.

Abstract Background Recent advances in circulating cell-free DNA (cfDNA) analysis from biofluids have opened new avenues for liquid biopsy (LB). However, current cfDNA LB assays are limited by the availability of existing information on established genotypes associated with tumor tissues. Certain cancers present with a limited list of established mutated cfDNA biomarkers, and thus, nonmutated cfDNA characteristics along with alternative biofluids are needed to broaden the available cfDNA targets for cancer detection. Saliva is an intriguing and accessible biofluid that has yet to be fully explored for its clinical utility for cancer detection. Methods In this report, we employed a low-coverage single stranded (ss) library NGS pipeline “Broad-Range cell-free DNA-Seq” (BRcfDNA-Seq) using saliva to comprehensively investigate the characteristics of salivary cfDNA (ScfDNA). The identification of cfDNA features has been made possible by applying novel cfDNA processing techniques that permit the incorporation of ultrashort, ss, and jagged DNA fragments. As a proof of concept using 10 gastric cancer (GC) and 10 noncancer samples, we examined whether ScfDNA characteristics, including fragmentomics, end motif profiles, microbial contribution, and human chromosomal mapping, could differentiate between these two groups. Results Individual and integrative analysis of these ScfDNA features demonstrated significant differences between the two cohorts, suggesting that disease state may affect the ScfDNA population by altering nuclear cleavage or the profile of contributory organism cfDNA to total ScfDNA. We report that principal component analysis integration of several aspects of salivary cell-free DNA fragmentomic profiles, genomic element profiles, end-motif sequence patterns, and distinct oral microbiome populations can differentiate the two populations with a p value of

Abstract Background Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD. Results: After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment. Conclusions Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1 .

Abstract Objective This review was conducted to assess the effectiveness of xylitol against Porphyromonas gingivalis anaerobic species, a key microbe contributing to periodontal disease pathogenesis. Material and Methods Relevant studies published on seven online databases (Cochrane, Ovid, Pubmed, Pubmed Central, Scopus, Google Scholar, and Web of Science) were included in accordance with the PRISMA guidelines. Inclusion criteria allowed all study designs involving xylitol and P. gingivalis, literature published since the year 2000, and all xylitol delivery forms. Results The initial search yielded 186 papers. After the removal of duplicates, five reviewers screened every article for eligibility and seven articles were selected for data extraction. Four out of seven included studies assessed the dose‐dependent effect of xylitol on P. gingivalis growth, two studies assessed the effect of xylitol on P. gingivalis‐induced cytokine expression, and one study assessed both domains. Conclusions From the in vitro studies included in this systematic review, there is some evidence of xylitol's inhibitory effect on P. gingivalis. However, more evidence derived from in vivo studies is required to confirm its effectiveness warranting their routine use.

Abstract Background Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12–17 year], nine children [6–11 year], and seven infants/early child [1–5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DLCO), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores. Results All 20 former ASCEND-Peds patients completed at least 2 years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (p

An experimental study is performed to determine the head mechanics of American football helmets equipped with novel fiber energy absorbing material (FEAM). FEAM-based padding materials have substrates of textile fabrics and foam made with nylon fibers using electro-static flocking process. Both linear and angular accelerations of the sport helmets are determined under impact loads using a custom-built linear impactor and instrumented head. The effectiveness of padding materials and vinyl nitrile (VN) foam for impact loads on six different head positions that simulate two helmeted sport athletes in real-time helmet-to-helmet strike/impact is investigated. A high-speed camera is used to record and track neck flexion angles and compare them with pad effectiveness to better understand the head kinematics of struck players at three different impact speeds (6 m/s, 8 m/s, and 10 m/s). At impact speed of 6 m/s and 8 m/s, the FEAM-based padding material of 60 denier fibers showed superior resistance for angular acceleration. Although novel pads of VN foam flocked with 60 denier fibers outperformed with lowest linear acceleration for most of the head positions at low impact speed of 6 m/s, VN foam with no fibers demonstrated excellent performance for linear acceleration at other two speeds.

Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.

This paper proposes a high voltage step-up DC/DC converter by combining a coupled inductor and a voltage multiplier rectifier. The input side of the proposed converter operates in an interleaved manner with two coupled inductors connected in parallel, and the output side is composed of a voltage multiplier rectifier where two voltage doubler rectifiers are merged in series. By changing the turns ratio of the coupled inductor of the proposed converter, the voltage gain can be increased, and additional voltage gain can be obtained by combining it with a voltage multiplier rectifier. Due to the passive lossless clamping performance of the proposed method, it is possible to recycle the leakage inductance energy of the coupled inductor and voltage stress reduction can be achieved along with zero current turn–ON and turn–OFF of switches and diodes. Finally, this paper evaluates the effectiveness and practicality of the proposed method by operating a prototype circuit with an input voltage of 20V, an output voltage of 400V, and an output power of 320W. The maximum efficiency of the proposed converter is 97.2% and the efficiency at maximum power is 94.1%.

There has been a movement to share and spread online lectures through OCW and MOOC systems. This movement would have been spread widely and adopted widely if those courses could be easily exchangeable with other platforms or services. If this function is available, learning activities, resources, learning outcomes can be accessed between different platforms and services. With this function, the credit exchange between different platforms or services will be easier. It also facilitates course sharing and circulation. Because the LMS is the basic platform for online classes, providing sharable and reusable learning activities, resources, and learning outcomes across the different LMSs is very demanding for online education. Analyzing LMS use in Korean universities, Moodle, Canvas, and domestic LMSs are founded to be the significant three kinds that are widely used in Korea. In this paper, a method of integrating Moodle, Canvas, and domestic LMS services is proposed. A central Moodle server is installed as the main LMS server, and the method to connect or complement with a central Moodle server is proposed for each different kind of LMS. LMS users can easily access a different kind of LMS as a form of imported course, tightly connected service, or log in as SSO. This proposition can be applied to various service fields such as KMOOC, KOCW, credit exchange, lecture exchange between universities, regional unification of online educational centers as a practical problem-solver.

Before Covid-19, the class model was divided into online, offline, and blended learning. Due to Covid-19, we have the only online class environment. We need a new online class model under the new circumstances. In the new model, all technology and educational methods need to be well-adapted, organized and harmonized to compensate for the absence of offline learning sessions. In this paper, we propose a new online class model. Because of the absence of offline sessions, the model emphasizes the integration of synchronous and asynchronous activities seamlessly and effectively. The model also emphasizes the instructor's role as a content prosumer because the instructor in the new model is either reusing other's and the one's own contents or supplying those contents for others. This model uses open-source solutions or free services like Moodle, OBS, Tubestory, and Snap Camera for both budget-saving and stability purposes. It actively uses Moodle's monitoring capability and adopts various learning technologies. It consists of three activity sessions: a pre-Zoom session, a Zoom session, and a post-Zoom session. Each session is composed of modules that describe the process and action for the class. The process, methods, and techniques for each module are explained in this paper. The official students survey for class evaluation held by Kongju national university showed that the new class model's application obtained a higher score than the same class of the previous year that is performed by conventional teaching.

The electro-fracture studies on jute/epoxy composites are conducted for monitoring damage under mode-I interlaminar fracture loading condition. A well-connected electrical network is built inside the composites by electro-flocking microcarbon fibers between the laminates and dispersing carbon nanotubes in the matrix. The effect of carbon fiber length and density on the electro-fracture behavior is studied. The change in electrical resistance is measured using a novel four-probe method through the thickness direction of cantilever beam test specimen. Results show that the maximum increase of fracture initiation toughness is 75% by the composite with carbon fibers length of 350 μm and fiber density of 2000 fibers/mm2 compare to composites with no carbon fibers. For all composite types, the increase in resistance is not noticeable before crack initiation. The cycles of fracture energy build up and release during the crack propagation are accurately detected onsite by the composite with carbon fiber length of 350 μm and fiber density of 2000 fibers/mm2.

Summary: The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013–2018), Phase 2 of the program (ERCC2, 2019–2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2’s current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

S100A10 (p11) is an emerging player in the neurobiology of depression and antidepressant actions. p11 was initially thought to be a modulator of serotonin receptor (5-HTR) trafficking and serotonergic transmission, though newly identified binding partners of p11 and neurobiological studies of these proteins have shed light on multifunctional roles for p11 in the regulation of glutamatergic transmission, calcium signaling and nuclear events related to chromatin remodeling, histone modification, and gene transcription. This review article focuses on direct binding partners of p11 in the brain including 5-HTRs, mGluR5, annexin A2, Ahnak, Smarca3, and Supt6h, as well as their roles in neuronal function, particularly in the context of depressive-like behavior as well as behavioral effects of antidepressant drug treatments in mice. In addition, we discuss neurobiological insights from recently uncovered p11 pathways in multiple types of neurons and non-neuronal cells and cast major remaining questions for future studies.

Summary: Plasma cell-free DNA is being widely explored as a biomarker for clinical screening. Currently, methods are optimized for the extraction and detection of double-stranded mononucleosomal cell-free DNA of ∼160bp in length. We introduce uscfDNA-seq, a single-stranded cell-free DNA next-generation sequencing pipeline, which bypasses previous limitations to reveal a population of ultrashort single-stranded cell-free DNA in human plasma. This species has a modal size of 50nt and is distinctly separate from mononucleosomal cell-free DNA. Treatment with single-stranded and double-stranded specific nucleases suggests that ultrashort cell-free DNA is primarily single-stranded. It is distributed evenly across chromosomes and has a similar distribution profile over functional elements as the genome, albeit with an enrichment over promoters, exons, and introns, which may be suggestive of a terminal state of genome degradation. The examination of this cfDNA species could reveal new features of cell death pathways or it can be used for cell-free DNA biomarker discovery.

Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly established. Here, we show behavioral outcomes of chronic social defeat stress (CSDS) are mediated by differential neuronal activity and gene expression in hippocampal PV neurons in mice. Using in vivo electrophysiology and chemogenetics, we find increased PV neuronal activity in the ventral dentate gyrus is required and sufficient for behavioral susceptibility to CSDS. PV neuron-selective translational profiling indicates mitochondrial oxidative phosphorylation is the most significantly altered pathway in stress-susceptible versus resilient mice. Among differentially expressed genes associated with stress-susceptibility and resilience, we find Ahnak, an endogenous regulator of L-type calcium channels which are implicated in the regulation of mitochondrial function and gene expression. Notably, Ahnak deletion in PV neurons impedes behavioral susceptibility to CSDS. Altogether, these findings indicate behavioral effects of chronic stress can be controlled by selective modulation of PV neuronal activity or a regulator of L-type calcium signaling in PV neurons.

In this paper, a new type of interleaved high step-up converter including a coupled inductor is proposed. The proposed converter has an interleaved configuration on the input side to reduce the ripple of the input current and increase the power level. Moreover, a stacked structure on the output side provides a high input/output (I/O) voltage gain. In addition, the proposed converter can avoid an extreme duty cycle, causing larger conduction losses, by combining a coupled inductor and a lossless clamp circuit with an interleaved method. These increase the efficiency by making the semiconductor device a low voltage stress and allowing the use of components with low voltage ratings. Also, the energy stored in the leakage inductor in the coupled inductor can be recycled to the output side, the MOSFETs can be partially ZCS turned ON, and the diode reverse recovery problem can be alleviated. Finally, a laboratory prototype circuit with an input voltage of 24V, an output voltage of 400V and an output of 500W was implemented to demonstrate the performance of the proposed converter.

In this paper, a high-efficiency DC/DC converter with low voltage stress is designed for green power applications. The proposed non-isolated high step-up DC/DC converter combines the advantages of switched capacitors, coupling inductors, and voltage multiplier techniques. Adding the cells of the switched capacitor not only increases the voltage gain but reduces the voltage stress of the semiconductor devices. High voltage gain can be achieved by adding a coupled inductor method to adjust the turns ratio. When these are combined with a voltage multiplier circuit, the leakage energy of the coupled inductor is recirculated to the output terminal with lossless passive clamping performance. The leakage inductance of the coupled inductor controls the current dropping rate of the output diode turn OFF so that the reverse-recovery problem is mitigated. The proposed converter integrates these three techniques to achieve high voltage gain without operating at maximum duty cycle. In addition, switching loss reduction is realized through zero current switching turn ON soft switching performance with low voltage stress of semiconductor devices. Finally, this paper verifies the performance of the proposed converter for theoretical analysis by using a 35~45V input, 380V output, and 1kW power prototype circuit.

Alcohol consumption is associated with an increased risk of several cancers, including oral/oropharyngeal squamous cell carcinoma (OSCC). Alcohol also enhances the progression and aggressiveness of existing cancers; however, its underlying molecular mechanism remains elusive. Especially, the local carcinogenic effects of alcohol on OSCC in closest contact with ingestion of alcohol are poorly understood. We demonstrated that chronic ethanol exposure to OSCC increased cancer stem cell (CSC) populations and their stemness features, including self-renewal capacity, expression of stem cell markers, ALDH activity, and migration ability. The ethanol exposure also led to a significant increase in aerobic glycolysis. Moreover, increased aerobic glycolytic activity was required to support the stemness phenotype of ethanol-exposed OSCC, suggesting a molecular coupling between cancer stemness and metabolic reprogramming. We further demonstrated that chronic ethanol exposure activated NFAT (nuclear factor of activated T cells) signaling in OSCC. Functional studies revealed that pharmacological and genetic inhibition of NFAT suppressed CSC phenotype and aerobic glycolysis in ethanol-exposed OSCC. Collectively, chronic ethanol exposure promotes cancer stemness and aerobic glycolysis via activation of NFAT signaling. Our study provides a novel insight into the roles of cancer stemness and metabolic reprogramming in the molecular mechanism of alcohol-mediated carcinogenesis.

Alcohol (ethanol, EtOH) consumption during pregnancy can result in fetal alcohol spectrum disorders (FASDs), which are characterized by prenatal and postnatal growth restriction and craniofacial dysmorphology. Recently, cell-derived extracellular vesicles, including exosomes and microvesicles containing several species of RNAs (exRNAs), have emerged as a mechanism of cell-to-cell communication. However, EtOH's effects on the biogenesis and function of non-coding exRNAs during fetal development have not been explored. Therefore, we studied the effects of maternal EtOH exposure on the composition of exosomal RNAs in the amniotic fluid (AF) using rat fetal alcohol exposure (FAE) model. Through RNA-Seq analysis we identified and verified AF exosomal miRNAs with differential expression levels specifically associated with maternal EtOH exposure. Uptake of purified FAE AF exosomes by rBMSCs resulted in significant alteration of molecular markers associated with osteogenic differentiation of rBMSCs. We also determined putative functional roles for AF exosomal miRNAs (miR-199a-3p, miR-214-3p and let-7g) that are dysregulated by FAE in osteogenic differentiation of rBMSCs. Our results demonstrate that FAE alters AF exosomal miRNAs and that exosomal transfer of dysregulated miRNAs has significant molecular effects on stem cell regulation and differentiation. Our results further suggest the usefulness of assessing molecular alterations in AF exRNAs to study the mechanisms of FAE teratogenesis that should be further investigated by using an in vivo model.

ObjectiveTo evaluate the association between balance function and asymmetry of knee extension strength in an elderly Korean population.MethodsThe strength of the knee extensors in each leg was measured in 306 community-dwelling elderly subjects (age, 76.70±4.85 years) and 25 young healthy subjects (age, 34.23±8.93 years). Based on the difference in strength of both legs, the elderly subjects were divided into symmetric (n=128) and asymmetric (n=178) strength groups using an asymmetry cutoff 20%. We determined the postural control ability of the subjects using InBody posturography, Berg Balance Scale (BBS), Timed Up and Go test (TUG) and Short Physical Performance Battery (SPPB). The sway index (SI) of the subjects in four positions was assessed using posturography.ResultsThe group with asymmetric strength presented a significantly higher SI than the group with symmetric strength, in the normal position with eyes open and eyes open on pillows. In the normal position with the eyes closed and in postures with the eyes closed on pillows, the statistical analysis revealed no significant differences between the two groups. The three tests for physical performance (BBS, TUG, and SPPB) show no statistically significant difference between the two groups.ConclusionThe asymmetric strength group showed a significantly lower balance than the group with symmetric strength based on several posturographic parameters. Ambulatory elderly individuals with asymmetry in knee extension strength, showed deficits in balance control even in normal clinical tests.

An improved high step-down DC-DC converter for charging the batteries in an electric vehicle application is proposed in this paper. It adopts the topology of the conventional full-bridge converter, which has a coupled inductor current-doubler rectifier as the secondary side of the transformer. In addition, four power switches are driven using a phase-shifting technique. The proposed converter can achieve a high step-down voltage with low-voltage stress on the rectifier diodes. In addition, the coupled inductor current-doubler rectifier of the secondary side can reduce the ripple current and losses of the secondary side to achieve high efficiency. Furthermore, the proposed converter can overcome the drawbacks of the conventional full-bridge converter, such as switching loss caused by high switching frequency, duty-cycle loss, voltage stress, and numerous components, and can increase the efficiency with the soft-switching technique. A 600 W laboratory prototype of the proposed converter was manufactured. The results of the experiments performed with the prototype proved the effectiveness and validated the use of the proposed converter for better charging of electric vehicles.

Purpose Splicing factors play important roles in tumorigenesis. Serine/arginine-rich splicing factors 2 (SRSF2) and SRSF4 proteins, the members of SR family proteins, are dysregulated in various cancers. However, their protein expression levels and diagnostic values are unclear in colorectal cancer. Methods We quantified the protein levels of SRSF2, SRSF4, and previously known colon cancer markers (heterogeneous nuclear ribonucleoprotein A1 [HNRNPA1] and carcinoembryonic antigen [CEA]) in tumor compared with adjacent normal-looking areas (non-tumor) of the colon in Korean patients with colon cancer using immunoblot analysis. Results The protein levels of HNRNPA1 and CEA were remarkably increased in tumor compared to non-tumor tissue and up-regulated in all of the tumor samples. However, the protein levels of SRSF2 and SRSF4 in tumor tissue were reduced in contrast with those of non-tumor tissue. Conclusion None of the SRSF proteins were significantly different between the low (≤II) and high (>II) stages.

Memristor crossbar arrays were fabricated based on a Ti/HfO2/Ti stack that exhibited electroforming-free behavior and low device variability in a 10 x 10 array size. The binary states of high-resistance-state and low-resistance-state in the bipolar memristor device were used for the synaptic weight representation of a binarized neural network. The electroforming-free memristor was confirmed as being suitable as a binary synaptic device because of its higher device yield, lower variability, and less severe malfunction (for example, hard break-down) than the electroformed memristors based on a Ti/HfO2/Pt structure. The feasibly working binarized neural network adopting the electroforming-free binary memristors was demonstrated through simulation.

This study investigated the convergence of content and language integrated learning, translanguaging, and global citizenship education in an EFL tertiary English class. Conceptualized within translanguaging as an assemblage for meaning-making, machine translation was incorporated into the course in a way that EFL bilinguals could fully avail themselves of their linguistic repertoire for the learning of global citizenship and language. The analyses of thirty-three students' response essays and survey results demonstrate the success of MT as both a scaffold for bridging language-content gaps and a tool for language acquisition. Design features, perceived as important, were a careful introduction and training on MT use and teacher feedback on MT-assisted writing. Survey results emphasize the crucial role of the students' L1 in meaning-making. The study offers a practical guide for educators interested in using MT in L2 writing instruction and encourages further research on the theoretical and pedagogical applications of translanguaging in diverse EFL contexts.

Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 μg/mL significantly suppressed NO production at 100 μg/mL, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interferon-β at 200 μg/mL, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here, we show that altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact on neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors decreases neurogenesis in the dentate gyrus, while its overexpression increases neurogenesis. miR-17-92 affects neurogenesis by regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects induced by corticosterone in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors through regulation of neurogenesis and anxiety- and depression-like behaviors.

Epigenetic changes, such as alteration of DNA methylation patterns, have been proposed as a molecular mechanism underlying the effect of alcohol on the maintenance of adult stem cells. We have performed genome-wide gene expression microarray and DNA methylome analysis to identify molecular alterations via DNA methylation changes associated with exposure of human dental pulp stem cells (DPSCs) to ethanol (EtOH). By combined analysis of the gene expression and DNA methylation, we have found a significant number of genes that are potentially regulated by EtOH-induced DNA methylation. As a focused approach, we have also performed a pathway-focused RT-PCR array analysis to examine potential molecular effects of EtOH on genes involved in epigenetic chromatin modification enzymes, fibroblastic markers, and stress and toxicity pathways in DPSCs. We have identified and verified that lysine specific demethylase 6B (KDM6B) was significantly dysregulated in DPSCs upon EtOH exposure. EtOH treatment during odontogenic/osteogenic differentiation of DPSCs suppressed the induction of KDM6B with alterations in the expression of differentiation markers. Knockdown of KDM6B resulted in a marked decrease in mineralization from implanted DPSCs in vivo. Furthermore, an ectopic expression of KDM6B in EtOH-treated DPSCs restored the expression of differentiation-related genes. Our study has demonstrated that EtOH-induced inhibition of KDM6B plays a role in the dysregulation of odontogenic/osteogenic differentiation in the DPSC model. This suggests a potential molecular mechanism for cellular insults of heavy alcohol consumption that can lead to decreased mineral deposition potentially associated with abnormalities in dental development and also osteopenia/osteoporosis, hallmark features of fetal alcohol spectrum disorders.

Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase, PubMed, and the Cochrane database were searched using the key words SSNHL, prognostic, and biomarker. This search identified 4 articles in Embase, 28 articles in PubMed, and 36 in the Cochrane database. Of these 68 articles, 3 were duplicates and 37 were unrelated to the research topic. After excluding these articles, the remaining 28 articles were reviewed. Factors associated with SSNHL were divided into six categories: metabolic, hemostatic, inflammatory, immunologic, oxidative, and other factors. The associations between these factors with the occurrence of SSNHL and with patient prognosis were analyzed. Low monocyte counts, low neutrophil/lymphocyte ratio (NLR) and monocyte/high-density lipoproteins (HDL) cholesterol ratio (MHR), and low concentrations of fibrinogen, platelet glycoprotein (GP) IIIa, and TNF-α were found to be associated with good prognosis. However, these factors alone could not completely determine the onset of and recovery from SSNHL, suggesting the need for future basic and clinical studies.

Gamma scanning is a nuclear inspection technique widely used for troubleshooting industrial process equipments in refineries and petrochemicals. A radiation source and detector move vertically along the height of the vessel and the radiation readings are used to plot the graph of density profile. In recent years, many improvements have been added to this technique, but essentially the result of gamma scanning still consists of a 1-D density plot. Developed in 2012, the tomographic gamma scan uses image reconstruction techniques to show the result of gamma scan as a 2-D density distribution image. In this work, we present the current status of the technology and the results obtained by applying the technique to real operating process equipment. The results present images that match well with the 1-D density plots obtained by the conventional gamma scan and reveal process and operational problems that has never been visualized before with the traditional technique. The tomographic gamma scan can be immediately applied in practice with low financial investment.

The interfacial properties of Au/n-InP contacts with a thin layer of Al2O3 (0.7 or 2.7 nm) deposited by atomic layer deposition (ALD) were investigated using temperature-dependent current-voltage (I–V–T) and depth-resolved X-ray photoelectron spectroscopy (XPS) measurements. Schottky barrier inhomogeneity provided a good description of the charge transport at the interface of all the samples. Based on XPS analysis, the removal of native oxide occurred due to a self-cleaning effect via the ALD process, especially for the thicker Al2O3 layer. The significant diffusion of In into the Al2O3 of the thinner layer may have formed In2O3 and degraded the Al2O3 film. XPS analysis also showed that with increasing Al2O3 thickness, emission from In2O3 decreased while that from InPO4 increased.

Boerhavia diffusa L. is a green vegetable used as an herbal medicine in several Asian countries for the treatment of hepatitis, kidney stones, liver disorders, nephritis, urinary disorders, and urinary retention. In this study, the anti-inflammatory activity and the molecular inhibitory mechanisms of B. diffusa L. ethanol extract (Bd-EE) in vitro and in vivo were evaluated. Lipopolysaccharide (LPS)-activated peritoneal macrophage RAW264.7 cells and a mouse gastritis model induced by HCl/EtOH treatment were chosen to determine the in vitro and in vivo anti-inflammatory activities of Bd-EE. This extract (100 and 200 µg/ml) significantly (P

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

Background: Korean ginseng is an ethnopharmacologically valuable herbal plant with various biological properties including anticancer, antiatherosclerosis, antidiabetic, and anti-inflammatory activities. Since there is currently no drug or therapeutic remedy derived from Korean ginseng, we developed a ginsenoside-enriched fraction (AP-SF) for prevention of various inflammatory symptoms. Methods: The anti-inflammatory efficacy of AP-SF was tested under in vitro inflammatory conditions including nitric oxide (NO) production and inflammatory gene expression. The molecular events of inflammatory responses were explored by immunoblot analysis. Results: AP-SF led to a significant suppression of NO production compared with a conventional Korean ginseng saponin fraction, induced by both lipopolysaccharide and zymosan A. Interestingly, AP-SF strongly downregulated the mRNA levels of genes for inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase) without affecting cell viability. In agreement with these observations, AP-SF blocked the nuclear translocation of c-Jun at 2 h and also reduced phosphorylation of p38, c-Jun N-terminal kinase, and TAK-1, all of which are important for c-Jun translocation. Conclusion: Our results suggest that AP-SF inhibits activation of c-Jun-dependent inflammatory events. Thus, AP-SF may be useful as a novel anti-inflammatory remedy.

Background: Korean Red Ginseng (KRG) is a representative traditional herbal medicine with many different pharmacological properties including anticancer, anti-atherosclerosis, anti-diabetes, and anti-inflammatory activities. Only a few studies have explored the molecular mechanism of KRG-mediated anti-inflammatory activity. Methods: We investigated the anti-inflammatory mechanisms of the protopanaxadiol saponin fraction (PPD-SF) of KRG using in vitro and in vivo inflammatory models. Results: PPD-SF dose-dependently diminished the release of inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α, and prostaglandin E2], and downregulated the mRNA expression of their corresponding genes (inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase-2), without altering cell viability. The PPD-SF-mediated suppression of these events appeared to be regulated by a blockade of p38, c-Jun N-terminal kinase (JNK), and TANK (TRAF family member-associated NF-kappa-B activator)-binding kinase 1 (TBK1), which are linked to the activation of activating transcription factor 2 (ATF2) and interferon regulatory transcription factor 3 (IRF3). Moreover, this fraction also ameliorated HCl/ethanol/-induced gastritis via suppression of phospho-JNK2 levels. Conclusion: These results strongly suggest that the anti-inflammatory action of PPD-SF could be mediated by a reduction in the activation of p38-, JNK2-, and TANK-binding-kinase-1-linked pathways and their corresponding transcription factors (ATF2 and IRF3).

It has been reported that nicotine/alcohol alters epigenetic control and leads to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation of epigenetic machinery and leads to epigenetic alterations, which subsequently affect transcriptional regulation in oral epithelial stem cells. As an initiating step we have profiled transcriptomic alterations induced by the combinatory administration of EtOH and nicotine in primary normal human oral keratinocytes. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE57634. Our data provide comprehensive transcriptomic map describing molecular changes induced by EtOH and nicotine on normal human oral keratinocytes.

Human dental pulp stem cells (DPSCs) isolated from adult dental pulp are multipotent mesenchymal stem cells that can be directed to differentiate into osteogenic/odontogenic cells and also trans-differentiate into neuronal cells. The utility of DPSC has been explored in odontogenic differentiation for tooth regeneration. Alcohol abuse appears to lead to periodontal disease, tooth decay and mouth sores that are potentially precancerous. Persons who abuse alcohol are at high risk of having seriously deteriorated teeth, gums and compromised oral health in general. It is currently unknown if alcohol exposure has any impact on adult stem cell maintenance, stem cell fate determination and plasticity, and stem cell niche environment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE57255. Our data provide transcriptomic changes that are occurring by EtOH treatment of DPSCs at 24-hour and 48-hour time point.

Potential teratogenic effects of alcohol on fetal development have been documented. Especially studies have demonstrated deleterious effect of ethanol exposure on neuronal development in animal models and on the maintenance and differentiation of neuronal precursor cells derived from stem cells. To better understand the molecular effect of alcohol on the process of neural differentiation, we have performed gene expression microarray analysis on human embryonic stem cells being directed to neural rosettes and neural precursor cells in the presence of ethanol treatment. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE56906. Our data provide scientific insight on potential molecular effects of fetal alcohol exposure on neural differentiation of early embryo development.

The electrical switching behavior of the GeTe phase-changing material grown by atomic layer deposition is characterized for the phase change random access memory (PCRAM) application. Planar-type PCRAM devices are fabricated with a TiN or W bottom electrode (BE). The crystallization behavior is characterized by applying an electrical pulse train and analyzed by applying the Johnson−Mehl−Avrami kinetics model. The device with TiN BE shows a high Avrami coefficient (>4), meaning that continuous and multiple nucleations occur during crystallization (set switching). Meanwhile, the device with W BE shows a smaller Avrami coefficient (~3), representing retarded nucleation during the crystallization. In addition, larger voltage and power are necessary for crystallization in case of the device with W BE. It is believed that the thermal conductivity of the BE material affects the temperature distribution in the device, resulting in different crystallization kinetics and set switching behavior.

Anthraquinone compounds are one of the abundant polyphenols found in fruits, vegetables, and herbs. However, the in vivo anti-inflammatory activity and molecular mechanisms of anthraquinones have not been fully elucidated. We investigated the activity of anthraquinones using acute inflammatory and nociceptive experimental conditions. Anthraquinone-2-carboxylic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA), one of the major anthraquinones identified from Brazilian taheebo, ameliorated various inflammatory and algesic symptoms in EtOH/HCl- and acetylsalicylic acid- (ASA-) induced gastritis, arachidonic acid-induced edema, and acetic acid-induced abdominal writhing without displaying toxic profiles in body and organ weight, gastric irritation, or serum parameters. In addition, AQCA suppressed the expression of inflammatory genes such as cyclooxygenase- (COX-) 2 in stomach tissues and lipopolysaccharide- (LPS-) treated RAW264.7 cells. According to reporter gene assay and immunoblotting analyses, AQCA inhibited activation of the nuclear factor- (NF-) κB and activator protein- (AP-) 1 pathways by suppression of upstream signaling involving interleukin-1 receptor-associated kinase 4 (IRAK1), p38, Src, and spleen tyrosine kinase (Syk). Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs.

Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol's effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event associated with alcohol-related peripheral neuropathy of an enhanced nociceptive response.