An FPGA-Based ECU for Remote Reconfiguration in Automotive Systems.

Growing interest in intelligent vehicles is leading automotive systems to include numerous electronic control units (ECUs) inside. As a result, efficient implementation and management of automotive systems is gaining importance. Flexible updating and reconfiguration of ECUs is one appropriate strategy for these goals. Software updates to the ECUs are expected to improve performance and bug handling, but there are limitations due to the fixed hardware circuit. By applying hardware-reconfigurable ECUs to the automotive system, patches that are not able to be handled with only software updates are enabled. In this paper, a remotely hardware-reconfigurable ECU for automotive systems is proposed. The proposed ECU is implemented with a field programmable gate array (FPGA) and microcontroller unit (MCU) to support in-system reconfiguration (ISR). The communication interface between the FPGA and MCU employs Zipwire communication for high speed and resilient communication. For the Zipwire communication, a Zipwire controller is designed and implemented in the FPGA. The proposed hardware-reconfigurable ECU was successfully implemented, and feasibility was demonstrated.

Rapid Detection of Avian Influenza Virus by Fluorescent Diagnostic Assay using an Epitope-Derived Peptide.

Currently, the point of care testing (POCT) is not fully developed for subtype-specific avian influenza virus detection. In this study, an H5N1 hemaglutinin 1 (HA1) epitope (P0: KPNDAINF) and three modified peptides (P1: KPNTAINF, P2: KPNGAINF, P3: KPNDAINDAINF) were evaluated as POCT elements for rapid detection of avian influenza virus. Based on modeling predictions by Autodock Vina, binding affinity varied depending on alteration of one amino acid in these peptides. The binding energy of P2 indicated its potential for a strong interaction with HA. Fluorescence-linked immunosorbent assay experimentally demonstrated the interaction between these peptides and virus. The four peptides interacted with HA1 of H5N3 with different binding affinities with P2 showing the strongest binding affinity. When P0 and P2 peptides were used in rapid fluorescent immunochromatographic test (FICT) as detection elements, the inter-assay coefficients of variation (CV) indicated that P2-linked FICT was more acceptable than the P0-linked FICT in the presence of human specimens. Antibody pair-linked FICT was influenced by clinical samples more than the P2-linked FICT assay, which showed a 4-fold improvement in the detection limit of H5N3 and maintained H5 subtype-specificity. Compared to the rapid diagnostic test (RDT) which is not specific for influenza subtypes, P2-linked FICT could increase virus detection. In conclusion, results of this study suggest that HA epitope-derived peptides can be used as alternatives to antibodies for a rapid fluorescent diagnostic assay to detect avian influenza virus.

Rapid detection of avian influenza A virus by immunochromatographic test using a novel fluorescent dye.

Sensitive and rapid diagnostic systems for avian influenza (AI) virus are required to screen large numbers of samples during a disease outbreak and to prevent the spread of infection. In this study, we employed a novel fluorescent dye for the rapid and sensitive recognition of AI virus. The styrylpyridine phosphor derivative was synthesized by adding allyl bromide as a stable linker and covalently immobilizing it on latex beads with antibodies generating the unique Red dye 53-based fluorescent probe. The performance of the innovative rapid fluorescent immnunochromatographic test (FICT) employing Red dye 53 in detecting the AI virus (A/H5N3) was 4-fold and 16-fold higher than that of Europium-based FICT and the rapid diagnostic test (RDT), respectively. In clinical studies, the presence of human nasopharyngeal specimens did not alter the performance of Red dye 53-linked FICT for the detection of H7N1 virus. Furthermore, in influenza A virus-infected human nasopharyngeal specimens, the sensitivity of the Red dye 53-based assay and RDT was 88.89% (8/9) and 55.56% (5/9) relative to rRT-PCR, respectively. The photostability of Red dye 53 was higher than that of fluorescein isothiocyanate (FITC), showing a stronger fluorescent signal persisting up to 8min under UV. The Red dye 53 could therefore be a potential probe for rapid fluorescent diagnostic systems that can recognize AI virus in clinical specimens.

Discovery of gastric cancer specific biomarkers by the application of serum proteomics.

Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity.

Preparation of O2 Plasma Treated Polycaprolactone/Nano TiO2 Composites and In Vitro Bioactivity.

Polycaprolactone (PCL)/TiO2 composite films (PTCFs) were prepared by a solvent casting method at various concentrations of TiO2 (1, 3, 5, and 10 wt%) and then treated using oxygen plasma. The hydrophilicity of the oxygen plasma treated PTCFs increased as the treatment time was increased, due to the oxygen induced production of polar species at the surface of the PTCFs. In vitro bioactivities of the composite films were examined by immersion in simulated body fluid for up to 7 days. It was found that the oxygen plasma treatment significantly influenced the in vitro bioactivity of the PTCFs.

Synthesis of ZnS Microspheres by Template-Free Hydrothermal Method for Photocatalytic Reaction.

In this work, ZnS microspheres consisting of nanoblocks were synthesized by a simple, template-free approach employing a hydrothermal reaction at different temperatures, using Zn(CH3COO)2 and Na2S2O3 · 5H2O as starting materials in the aqueous solution. The synthesized samples were characterized using field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET). The photocatalysts were evaluated using photodecomposition of methylene blue under UV-C light. The photocatalytic degradation rate followed a pseudo-first-order equation. The kinetic constant (k1) of the ZnS microspheres was 5.43 x 10(-2) min(-1).

Characteristics of Plasma Treated Electrospun Polycaprolactone (PCL) Nanofiber Scaffold for Bone Tissue Engineering.

Polycaprolactone (PCL) nanofibers (PCL-NF) with uniform fibrous structure were fabricated by electrospinning. However, PCL-NF has hydrophobic surface, lacks functional groups and hence it is not a good substrate for cell adhesion. To improve the cell adhesion, PCL-NF surfaces were modified by low pressure RF discharge plasma treatment using monomer such as acrylic acid or oxygen gas. The plasma treated PCL-NFs improved the wettability and cell proliferation.

Effects of by-product feed-based silage on feeding, rumination, and excretion in growing Hanwoo heifers.

This study investigated the effects of feeding by-product feed (BF)-based silage on the behavior of growing Hanwoo heifers. Twelve Hanwoo heifers (13.2 months-old, 315 kg body weight; four heifers per pen) were assigned to three diets: a rice straw (RS) diet (concentrate mix and free access to RS), a RS and BF-based silage (RSBFS) diet (concentrate mix and free access to RS and BF-based silage), and a BF-based silage (BFS) diet (concentrate mix and free access to BF-based silage). Behavior was recorded for 5 days using camcorders. Compared to the RS group, the BFS group showed 21.7% higher dry matter intake, shorter feeding, rumination, and chewing times, as well as longer resting time (p < 0.05). Although all groups exhibited similar drinking, urination, and defecation frequencies, the BFS group exhibited higher feeding rates, rumination efficiency, and chewing efficiency than the RS group (p < 0.05). Compared to the BFS group, the RSBFS group showed higher peNDF8.0 intake (15.2% vs. 25.0% dry matter intake), longer feeding and sitting times, lower defecation frequency (p < 0.05), and similar rumination efficiency. In conclusion, complete replacement of conventional RS with BF-based silage reduced rumination and chewing activity in growing Hanwoo heifers, and BF-based silage feeding with large-particle straw is an effective approach in improving heifer behavior.

A key lysine residue in the AXH domain of ataxin-1 is essential for its ubiquitylation.

Spinocerebellar ataxia type 1 (SCA1), an autosomal-dominant neurodegenerative disorder, is caused by expansion of the polyglutamine tract within ataxin-1 (ATXN1). The AXH domain of ATXN1 can mediate neurodegeneration through its interaction with other proteins. We have previously showed that the ubiquitin-conjugating enzyme UbcH6 modulates the transcriptional repression activity of ATXN1 through ubiquitylation. In the present study, we sought to identify sites in the AXH domain that are ubiquitylated by UbcH6. Systematic replacement of each lysine residue in the AXH domain revealed that the lysine at 589 (K589) of ATXN1 is essential for its ubiquitylation by UbcH6. Mass spectrometry studies further confirmed the ubiquitylation site. Interestingly, protein aggregation was significantly enhanced in mutant AXH K589R, implying that the aggregation is strongly associated with the level of ATXN1 expression. Our study may suggest a therapeutic potential of UbcH6 in the treatment of SCA1.

Analysis of nitrated proteins in Saccharomyces cerevisiae involved in mating signal transduction.

Protein tyrosine nitration (PTN) is a PTM that regulates signal transduction and inflammatory responses, and is related to neurodegenerative and cardiovascular diseases. The cellular function of PTN remains unclear because the low stoichiometry of PTN limits the identification and quantification of nitrated peptides. Effective enrichment is an important aspect of PTN analysis. In this study, we analyzed the in vivo nitroproteome elicited by mating signal transduction in Saccharomyces cerevisiae using a novel chemical enrichment method followed by LC-MS/MS. Nitroproteome profiling successfully identified changes in the nitration states of 14 proteins during mating signal transduction in S. cerevisiae, making this the first reported in vivo nitroproteome in yeast. We investigated the biological functions of these nitroproteins and their relationships to mating signal transduction in S. cerevisiae using a protein-protein interaction network. Our results suggest that PTN and denitration may be involved in nonreactive nitrogen species-mediated signal transduction and can provide clues for understanding the functional roles of PTN in vivo.

The standardized BHH10 extract, a combination of Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, reverses bone mass and metabolism in a rat model of postmenopausal osteoporosis.

Jasin-hwan-gagambang (BHH10), a modified prescription of Jasin-hwan, contains Astragalus membranaceus, Cinnamomum cassia, and Phellodendron amurense, and it has been traditionally used to treat osteoporosis and other inflammatory diseases. In this study, we systematically investigated the protective effects of BHH10 in ovariectomy (OVX)-induced rats. Sprague-Dawley rats were randomly divided into sham and OVX subgroups. The rats in the OVX group were treated with vehicle, BHH10, alendronate (ALN), and 17ß-estradiol (E2). BHH10 treatment significantly inhibited OVX-induced increases in body weight and uterus atrophy. In addition, it significantly increased the bone mineral density (BMD) and prevented a decrease in trabecular bone volume, connectivity density, trabecular number, thickness, and separation at the total femur and femur neck. The OVX rats showed significant decreases in the serum levels of calcium and phosphorous and significant increases in the serum levels of cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, osteocalcin, C-telopeptide type 1 collagen, and bone morphogenetic protein-2. These changes were significantly reduced to near sham levels by administration of BHH10 to OVX rats. BHH10-treated rats had a greater bone mass, a better structural architecture of the bone, and higher levels of biochemical markers of the bone than did the ALN-treated or E2-treated rats. These results suggest that BHH10 reverses osteoporosis in OVX rats by stimulating bone formation or regulating bone resorption and is not associated with toxicity.

Phospholipids of tumor extracellular vesicles stratify gefitinib-resistant nonsmall cell lung cancer cells from gefitinib-sensitive cells.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib are one of gold standard treatment options for nonsmall-cell lung cancer (NSCLC) patients, which eventually fail due to the acquired resistance and relapse because of the development of secondary activating mutations such as T790M in EGFR. Predicting chemo-responsiveness of cancer patients provides a major challenge in chemotherapy. The goal of the present study is to determine whether phospholipid signatures of tumor extracellular vesicles (EV) are associated with gefitinib-resistance of NSCLC. A sophisticated MS-based shotgun lipidomic assays were performed for in-depth analysis of the lipidomes of gefitinib-resistant (PC9R) and responsive (PC9) NSCLC cells and their shed EV from these cell lines (PC9EV or PC9REV). Lipid MALDI-MS analysis showed that EV phospholipid composition was significantly distinct in PC9R, compared to PC9 cells. Following statistical analyses has identified 35 (20 positive and 15 negative ion mode) differentially regulated lipids, which are significantly over- or underexpressed in PC9R EV, compared to PC9 EV (p value < 0.01, fold change > 1.5). Our phospholipid signatures suggest that EV associates with drug sensitivity, which is worthy of additional investigation to assess chemoresistance in patients with NSCLC treated with anti-EGFR TKIs.

Acupuncture for postoperative pain in laparoscopic surgery: a systematic review protocol.

INTRODUCTION: This review aims to evaluate the effectiveness and safety of acupuncture for patients with postoperative pain after laparoscopic surgery. METHODS AND ANALYSIS: We will search the following databases from their inception to October 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), three Chinese databases (China National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and the Wanfang database), one Japanese database (Japan Science and Technology Information Aggregator, Electronic (J-STAGE)) and eight Korean databases (Korean Association of Medical Journal Edition, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, Database Periodical Information Academic, Korean National Assembly Digital Library, Oriental Medicine Advanced Searching Integrated System and Korean Traditional Knowledge Portal). All randomised controlled trials of acupuncture for postoperative pain after laparoscopic surgery will be considered for inclusion. The risk of bias and reporting quality will be assessed using the Cochrane risk of bias tool, the Consolidated Standards of Reporting Trials (CONSORT) and the revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The risk ratio for dichotomous data and mean difference or standard mean difference for continuous data will be calculated with 95% CIs. DISSEMINATION: The results of this review will be disseminated through peer-reviewed publication or conference presentation. Our findings will summarise the current evidence of acupuncture to treat postoperative pain after laparoscopic surgery, and may provide important guidance for acupuncture usage after laparoscopic surgery for clinicians and patients. TRIAL REGISTRATION NUMBER: PROSPERO 2014: CRD42014010825.

Formononetin attenuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway.

Formononetin (1), a plant-derived phytoestrogen, possesses bone protective properties. To address the potential therapeutic efficacy and mechanism of action of 1, we investigated its antiosteoclastogenic activity and its effect on nuclear factor-kappaB ligand (RANKL)-induced bone-marrow-derived macrophages (BMMs). Compound 1 markedly inhibited RANKL-induced osteoclast differentiation in the absence of cytotoxicity, by regulating the expression of osteoprotegerin (OPG) and RANKL in BMMs and in cocultured osteoblasts. Compound 1 significantly inhibited RANKL-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) in a concentration-dependent manner. These effects were accompanied by a decrease in RANKL-induced activation of the NF-κB p65 subunit, degradation of inhibitor κBα (IκBα), induction of NF-κB, and phosphorylation of AKT, extracellular-signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). NF-κB siRNA suppressed AKT, ERK, JNK, and p38 MAPK phosphorylation. Furthermore, 1 significantly suppressed c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), key transcription factors during osteoclastogenesis. SP600125, a specific inhibitor of JNK, reduced RANKL-induced expression of phospho-c-Jun, c-Fos, and NFATc1 and inhibited osteoclast formation. These results suggested that 1 acted as an antiresorption agent by blocking osteoclast activation.

Arginine enhances osteoblastogenesis and inhibits adipogenesis through the regulation of Wnt and NFATc signaling in human mesenchymal stem cells.

Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs). Arginine potently induced the expression of type Iα1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2), DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG) content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and fatty acid binding protein 4 (Fabp4). This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway.

Extracellular vesicles shed from gefitinib-resistant nonsmall cell lung cancer regulate the tumor microenvironment.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), including gefitinib, are the first-line treatment of choice for nonsmall cell lung cancer patients who harbor activating EGFR mutations, however, acquired resistance to EGFR-TKIs is inevitable. The main objective of this study was to identify informative protein signatures of extracellular vesicles (EV) derived from gefitinib-resistant nonsmall cell lung cancer cells using proteomics analysis. Nano-LC-MS/MS analysis identified with high confidence (false discovery rate < 0.05, fold change ≥2) 664 EV proteins enriched in PC9R cells, which are resistant to gefitinib due to EGFR T790M mutation. Computational analyses suggested components of several signal transduction mechanisms including the AKT (also PKB, protein kinase B)/mTOR (mechanistic target of rapamycin) pathway are overrepresented in EV from PC9R cells. Treatment of recipient cells with EV harvested from PC9R cells increased phosphorylation of signaling molecules, and enhanced proliferation, invasion, and drug resistance to gefitinib-induced apoptosis. Dose- and time-dependent pharmaceutical inhibition of AKT/mTOR pathway overcame drug resistance of PC9R cells and those of H1975 exhibiting EGFR T790M mutation. Our findings provide new insight into an oncogenic EV protein signature regulating tumor microenvironment, and will aid in the development of novel diagnostic strategies for prediction and assessment of gefitinib resistance.

A novel vanadosilicate with hexadeca-coordinated Cs(+) ions as a highly effective Cs(+) remover.

The effective removal of (137) Cs(+)  ions from contaminated groundwater and seawater and from radioactive nuclear waste solutions is crucial for public health and for the continuous operation of nuclear power plants. Various (137) Cs(+)  removers have been developed, but more effective (137) Cs(+)  removers are still needed. A novel microporous vanadosilicate with mixed-valence vanadium (V(4+) and V(5+) ) ions is now reported, which shows an excellent ability for Cs(+)  capture and immobilization from groundwater, seawater, and nuclear waste solutions. This material is superior to other known materials in terms of selectivity, capacity, and kinetics, and at very low Cs(+)  concentrations, it was found to be the most effective material for the removal of radioactive Cs(+)  ions under the test conditions. This novel vanadosilicate also contains hexadeca-coordinated Cs(+)  ions, which corresponds to the highest coordination number ever described.

Bee venom treatment for refractory postherpetic neuralgia: a case report.

OBJECTIVE: Bee venom has been reported to have antinociceptive and anti-inflammatory effects in experimental studies. However, questions still remain regarding the clinical use of bee venom. This report describes the successful outcome of bee venom treatment for refractory postherpetic neuralgia. PATIENT: A 72-year-old Korean man had severe pain and hypersensitivity in the region where he had developed a herpes zoster rash 2 years earlier. He was treated with antivirals, painkillers, steroids, and analgesic patches, all to no effect. INTERVENTION: The patient visited the East-West Pain Clinic, Kyung Hee University Medical Center, to receive collaborative treatment. After being evaluated for bee venom compatibility, he was treated with bee venom injections. A 1:30,000 diluted solution of bee venom was injected subcutaneously along the margins of the rash once per week for 4 weeks. RESULTS: Pain levels were evaluated before every treatment, and by his fifth visit, his pain had decreased from 8 to 2 on a 10-point numerical rating scale. He experienced no adverse effects, and this improvement was maintained at the 3-month, 6-month, and 1-year phone follow-up evaluations. CONCLUSION: Bee venom treatment demonstrates the potential to become an effective treatment for postherpetic neuralgia. Further large-sample clinical trials should be conducted to evaluate the overall safety and efficacy of this treatment.

Combined phospho- and glycoproteome enrichment in nephrocalcinosis tissues of phytate-fed rats.

RATIONALE: Protein post-translational modifications (PTMs) are directly involved in protein function and cellular activities. Among them, glycosylation and phosphorylation are particularly important modifications on proteins located at extracellular and intracellular domains, respectively. However, the combined detection using phospho- and glycoproteomics is limited mainly due to protocol differences. METHODS: In this study, we developed a novel method for both phospho- and glycoproteome detection from a single sample batch, in which a titanium dioxide cartridge was used to capture the phosphoproteome, and the flow-through solution was processed for capturing N-linked glycopeptides using hydrazide resin. RESULTS: By using 1 mg of protein from kidney tissue lysates from normal and diseased rats, we concurrently identified 437 glycosites/358 phosphosites and 468 glycosites/369 phosphosites in normal and disease kidneys, respectively, by liquid chromatography/tandem mass spectrometric analysis. CONCLUSIONS: Compared with individual PTM analyses, the combined PTM analysis clearly provides more broad implications for PTMs related to the pathological status and discovery of biomarker candidates. Furthermore, the combined protocol thoroughly showed its advantages in enrichment efficiency and biological interpretation compared with current methods.