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Osteosarcoma is the most common type of bone cancer. Multimodality treatment involving chemotherapy, radiotherapy and surgery is not effective enough to control osteosarcoma. Regorafenib, the oral multi-kinase inhibitor, has been shown to have positive efficacy on disease progression delay in chemotherapy resistant osteosarcoma patients. However anti-cancer effect and mechanism of regorafenib in osteosarcoma is ambiguous. Thus, the aim of this study is to investigate the efficacy and molecular mechanism of regorafenib on osteosarcoma in vitro and in vivo. Human osteosarcomas U-2 OS or MG-63 were treated with regorafenib, miltefosine (protein kinase B (AKT) inhibitor), or PD98059 (mitogen-activated protein/extracellular signal-regulated kinase (MEK) pathway inhibitor) for 24 or 48 h. Cell viability, apoptotic signaling transduction, tumor invasion, expression of tumor progression-associated proteins and tumor growth after regorafenib treatment were assayed by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, transwell assay, Western blotting assay and in vivo animal experiment, respectively. In these studies, we also indicated that regorafenib suppressed cell growth by prompting apoptosis of osteosarcoma cells, which is mediated through inactivation of ERK and AKT signaling pathways. After regorafenib treatment, downregulation of related genes in invasion (vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9)), proliferation (CyclinD1) and anti-apoptosis (X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia-1 (MCL-1), and cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (C-FLIP)) were found. Moreover, upregulation of caspase-3 and caspase-8 cleavage were also observed. In sum, we suggest that regorafenib has potential to suppress osteosarcoma progression via inactivation of AKT and ERK mediated signaling pathway.

Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anticancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF

Evaluation of insertion/deletion (InDel) regions by comparative chloroplast DNA (cpDNA) analysis of two endemic moth orchids, Phalaenopsis aphrodite and P. equestris, identified 15 highly variable cpDNA regions that could be served as useful markers for interspecific differentiation of moth orchids. In this study, we evaluated 31 cpDNA regions carrying simple sequence repeats (SSRs) or InDels from two moth orchids to reveal intraspecific markers for distinguishing the cultivars of P. equestris. In total, 18 of the cpDNA markers were variable among cultivars of P. equestris; 9 cpDNA markers were highly variable, with polymorphic information content ≥5.5. The petA-psbJ, psbB-psbT and rps16-trnQ markers showed the best discriminatory power; 11 P. equestris cultivars could be separated into at least five groups. From the sequences for six selected cpDNA regions, the rps16-trnQ and psbB-psbT intergenic spacers were the best DNA barcodes; 11 P. equestris cultivars could be separated into six distinct groups. Phylogenetic analysis revealed that P. equestris cultivars have evolved into two major lineages, and the species in the Stauroglottis and Amboinenses sections are in a non-monophyletic relationship. We have revealed a set of cpDNA markers that could be used for intraspecific identification and phylogenetic study of P. equestris cultivars.

Active epidermal growth factor receptors (EGFR) signaling mediates the progression of colorectal cancer (CRC) through activation of downstream kinases and transcription factors. The increased expression of EGFR was associated with worse prognosis in patients with metastatic CRC (mCRC). Regorafenib, the oral kinase inhibitor approved for the treatment of mCRC, has been shown to reduce activation of downstream kinases of EGFR signal pathway in hepatocellular carcinoma and osteosarcoma. However, whether EGFR inactivation was participates in regorafenib-inhibited progression of CRC still remaining ambiguous. The major purpose of present study was to verify effect of regorafenib on EGFR signaling-mediated progression of CRC. Here, we investigated the effect of regorafenib or erlotinib (EGFR inhibitor) on tumor cell growth, invasion ability, apoptotic, and EGFR signal transduction in CRC in vitro and in vivo. Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Both regorafenib and erlotinib significantly reduced cell invasion ability, activation of protein kinase C-δ (PKCδ), protein kinase B (AKT), extracellular signal-regulated kinases (ERK), and NF-κB. Regorafenib can trigger the inhibition of tumor cell growth and the induction of apoptosis through extrinsic/intrinsic apoptosis pathways. In addition, the expression of NF-κB-mediated proteins involved in tumor progression was also suppressed by regorafenib treatment. Taken together, regorafenib acts as a inhibitor of EGFR signaling that attenuated the activation of EGFR and EGFR related downstream signaling cascades in CRC. Our results suggested that the suppression of EGFR signaling was associated with regorafenib-inhibited progression of CRC.

We determined the mitochondrial genome of an endemic moth orchid, Phalaenopsis aphrodite subsp. formosana, and annotated the mitochondrial genes, studied gene expression and investigated the RNA editing status. The mitochondrial DNA (mtDNA) of moth orchid is approximately 576,203 bp, with 27 % and 9% of sequences derived from nucleus and plastid, respectively. The mtDNA encodes 38 protein-coding, 9 tRNA and 3 ribosomal RNA genes of mitochondrial origin. Up to 1032 RNA edits, with 1020 C-to-U and 12 U-to-C conversions, were identified from mitochondrial transcripts of leaf and floral tissues, the highest number reported so far in angiosperms. Overall, 941 edits were involved in protein-coding transcripts, and the 686 nucleotide conversions caused non-synonymous substitution. RNA editing in protein-coding transcripts mainly altered the amino acids and tended to increase the hydrophobicity as well as conservation among plant phylogeny. The remaining 91 RNA edits occurred in non–protein-coding transcripts such as untranslated regulatory regions and introns; some would affect the stability of secondary structures, which might play an important role in regulating gene expression. The average efficiency of RNA editing was significantly higher for protein-coding than non–protein-coding transcripts 69.1 % vs 44.2 %). At least 135 edits showed significant (≥ 20 %) differential editing between leaf and floral tissues, which suggested that unidentified tissue-specific factors might be required for regulating RNA editing in moth orchid. In addition, the mitochondrial gene expression varied among genes, tissue types and developmental stages in moth orchid.

Alkoholdehydrogenasen dienen als effektive Katalysatoren in der Herstellung optisch aktiver gamma-Hydroxy-delta-lactone auf Grundlage einer enantiokonvergenten dynamischen Redoxisomerisierung von einfach zugänglichen, racemischen Achmatowicz-Pyranonen. Durch die Nachahmung der traditionell Übergangsmetall-vermittelten "Borrowing-hydrogen"-Methodik zur Überführung von Hydridspezies innerhalb heterocyclischer Gerüste erlaubt diese chemoinspirierte, jedoch vollständig biokatalysierte Interpretation das bestehende Syntheserepertoire von Enzymen effektiv zu erweitern und bietet hierdurch neue Möglichkeiten in der Konstruktion von Multienzymkaskaden sowie im Design maßgeschneiderter Zellfabriken.

Efficient asymmetric bio-epoxidation of electron-deficient α,β-unsaturated ketones was realized via a tandem reduction-epoxidation-dehydrogenation cascade, which proceeds in a switchable manner to afford either chiral epoxy ketones or allylic epoxy alcohols with up to >99% yield and >99%ee.

Moth orchids (Phalaenopsis) are among the top-traded blooming potted plants in the world. To explore mitochondrial DNA (mtDNA) markers for species identification, we located simple sequence repeats in the mtDNA of Phalaenopsis aphrodite subsp. formosana and then pre-screened them for polymorphic markers by their comparison with corresponding mtDNA regions of P. equestris. The combination of 13 selected markers located in intergenic spacers could unambiguously distinguish 15 endemic moth orchids. Five most variable markers with polymorphic information content (PIC) ≥ 0.7 could be combined to classify 18 of 19 endemic moth orchids including parental strains most commonly used in breeding programs. The sequences of four selected mtDNA regions were highly variable, and one region (MT2) could be used to completely distinguish 19 endemic moth orchids. Though mitochondrial introns were highly conserved among moth orchids, evolutionary hotspots, such as variable simple sequence repeats and minisatellite repeats, were identified as useful markers. Furthermore, a marker technology was applied to reveal the maternal inheritance mode of mtDNA in the moth orchids. Moreover, phylogenetic analysis indicates that the mtDNA was nonmonophyletic below the Phalaenopsis genus. In summary, we have revealed a set of mtDNA markers that could be used for identification and phylogenetic study of Phalaenopsis orchids.

Comparative analysis of chloroplast DNA (cpDNA) between two endemic moth orchids in Taiwan, Phalaenopsis aphrodite subsp. formosana and P. equestris, previously revealed many evolutionary hotspots. In this study, we explored 27 pre-screened cpDNA regions to evaluate molecular markers for distinguishing Phalaenopsis species. Fifteen cpDNA markers were highly variable among moth orchids, with polymorphic information contents ≥8.0. The rps16-trnQ marker showed the best discrimatory power which 15 endemic moth orchids could be successfully separated into 13 groups. From the sequences of the seven selected cpDNA regions, the rps16-trnQ intergenic spacer was the best DNA barcode which 19 endemic moth orchids could be completely distinguished. The petN-psbM intergenic spacer could be better used as a DNA barcode to differentiate P. aphrodite subsp. formosana and P. amabilis. Additionally, the inheritance mode of cpDNA in moth orchids was maternally predominated. Phylogenetic analysis revealed non-monophyletic relationships below the Phalaenopsis genus level. In summary, we have revealed a set of cpDNA markers that could be used for identification and phylogenetic study of Phalaenopsis orchids.

To investigate the association between tumor response to thoracic radiotherapy and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma, we collected 48 patients treated between January 2010 and December 2013. Of the 18 patients with EGFR mutation, 15 (83.3%) had a single mutation, and three (16.7%) had double mutation. Different EGFR mutation subtypes exhibited different responses to radiotherapy. The identified double EGFR mutations were associated with reduction of residual tumor burden (RTB) after radiotherapy. In univariate analysis, EGFR mutations in exon 18, 20, and 21 and double EGFR mutation were significant factors predicting RTB. In multivariate analysis, exon 20 mutation was the only significant factor. Patients with EGFR mutation seemed to have longer mean overall survival (OS) compared to the group with wild-type EGFR (31.1 vs. 26.6 months, p=0.49). The median and mean OS in patients with double EGFR mutation vs. wild-type EGFR were 20.1 vs. 16.9 months and 28.9 vs. 26.6 months, respectively. Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy.

This study proposes to make protective vests with X-ray shielding effectiveness. X-ray shielding powders are coated onto sandwich air mesh fabrics (SAMF), which are then coated with another layer of powders to form a continuous surface; thus forming double-layer X-ray shielding fabric. The tensile strength of SAMF is first evaluated, after which a stereomicroscope and scanning electron microscope (SEM) observe the X-ray shielding fabric and double-layer X-ray shielding fabrics. Next, an X-ray shielding effect test measures them. The double-layer X-ray shielding fabrics are then tailored into X-ray shielding protective vests using vest patterns. The test results show that the X-ray shielding powders can combine well with SAMF by using urethane resin, and as a result, the X-ray shielding effectiveness is proportional to the content of the powders. The double-layer X-ray shielding fabrics exhibit an optimal X-ray shielding effectiveness due to their double-layer structure. The combination of SAMF provides flexibility to the protective vest regardless of the coating of X-ray shielding powders.

The effects and possible underlying mechanism of curcumin combined with radiation in human hepatocellular carcinoma (HCC) cellsin vitrowere evaluated. The effects of curcumin, radiation, and combination of both on cell viability, apoptosis, NF-κB activation, and expressions of NF-κB downstream effector proteins were investigated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), NF-κB reporter gene, mitochondrial membrane potential (MMP), electrophoretic mobility shift (EMSA), and Western blot assays in Huh7-NF-κB-luc2, Hep3B, and HepG2 cells. Effect of I kappa B alpha mutant (IκBαM) vector, a specific inhibitor of NF-κB activation, on radiation-induced loss of MMP was also evaluated. Results show that curcumin not only significantly enhances radiation-induced cytotoxicity and depletion of MMP but inhibits radiation-induced NF-κB activity and expressions of NF-κB downstream proteins in HCC cells. IκBαM vector also shows similar effects. In conclusion, we suggest that curcumin augments anticancer effects of radiation via the suppression of NF-κB activation.

To investigate the association between tumor response to thoracic radiotherapy and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma, we collected 48 patients treated between January 2010 and December 2013. Of the 18 patients with EGFR mutation, 15 (83.3%) had a single mutation, and three (16.7%) had double mutation. Different EGFR mutation subtypes exhibited different responses to radiotherapy. The identified double EGFR mutations were associated with reduction of residual tumor burden (RTB) after radiotherapy. In univariate analysis, EGFR mutations in exon 18, 20, and 21 and double EGFR mutation were significant factors predicting RTB. In multivariate analysis, exon 20 mutation was the only significant factor. Patients with EGFR mutation seemed to have longer mean overall survival (OS) compared to the group with wild-type EGFR (31.1 vs. 26.6 months, p=0.49). The median and mean OS in patients with double EGFR mutation vs. wild-type EGFR were 20.1 vs. 16.9 months and 28.9 vs. 26.6 months, respectively. Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy.

The study goal was to investigate effect of amentoflavone on nuclear factor-κB (NF-κB)-modulated metastatic mechanism in osteosarcoma U2OS cells. U2OS cells were treated with amentoflavone, NF-κB inhibitor, protein kinase B (PKB or AKT) inhibitor or mitogen-activated protein kinase (MAPK) inhibitor. Change of cell viability, NF-κB activation, expression of metastasis-associated proteins, signal transduction, and cell migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, NF-κB reporter gene assay, western blotting, and cell migration and invasion assays. The results demonstrated that inhibition of activation of extracellular signal-regulated kinases (ERK) was a key point for suppression of NF-κB-modulated metastatic mechanism. Amentoflavone significantly inhibited NF-κB activation, ERK phosphorylation, expression of metastasis-associated proteins, and cell migration and invasion. Our findings indicate that amentoflavone reduces metastatic potential through suppression of ERK and NF-κB activation in osteosarcoma U2OS cells.

The aim of the present study was to investigate the effects of regorafenib on the nuclear factor κ-light-chain-enhancer of activated B cells (NF)-κB-modulated expression of angiogenesis- and metastasis-associated proteins and cell invasion in human hepatocellular carcinoma SK-Hep1 cells. The SK-Hep1 cells were treated with different concentrations of NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4,6-diamine (QNZ) or regorafenib for 24 or 48 h. The effects of QNZ and regorafenib on cell viability, NF-κB activation, expression and secretion levels of angiogenesis- and metastasis-associated proteins and cell invasion were evaluated with MTT assays, western blotting, ELISA, gelatin zymography and cell invasion assays. The results demonstrated that QNZ and regorafenib significantly reduced the expression and secretion levels of the angiogenesis- and metastasis-associated proteins vascular endothelial growth factor, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-2 and MMP-9, NF-κB activation and cell invasion. In conclusion, the inhibition of NF-κB activation induces anti-angiogenic and antimetastatic effects in SK-Hep1 cells. Regorafenib reduces the level of expression and secretion of angiogenesis- and metastasis-associated proteins and cell invasion through the suppression of NF-κB activation in SK-Hep1 cells.

The synthesis of optically pure secondary epoxy alcohols from racemic allylic alcohols using a single whole-cell biocatalyst of recombinant Escherichia coli coexpressing three oxidoreductases is described. The cascade involves the concurrent action of a styrene monooxygenase that catalyzes the formation of the chiral epoxy group, and two alcohol dehydrogenases that fulfil the epimerisation of the hydroxy group. Two sets of alcohol dehydrogenases were each applied to couple with styrene monooxygenase in order to realize the epimerisation in a stereo-complementary manner. Excellent enantio- and diastereo-selectivities were achieved for most of the 12 substrates.

Sorafenib is effective for patients with advanced hepatocellular carcinoma (HCC) and particularly for those who are unsuitable to receive life-prolonging transarterial chemo-embolization. The survival benefit of sorafenib, however, is unsatisfactory. Vorinostat also known as suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor with anti-HCC efficacy in preclinical studies. SAHA induces nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in vitro, which may lead to cancer cell progression and jeopardize cytotoxic effect of SAHA in HCC. The goal of this study was to investigate whether sorafenib enhances SAHA cytotoxicity against HCC through inhibition of SAHA-induced NF-κB activity. The human HCC cell line Huh7 transfected with dual reporter genes, luciferase (luc) and thymidine kinase (tk) with NF-κB response elements, was co-transfected with red fluorescent protein (rfp) gene for non-invasive molecular imaging to assess NF-κB activity and living cells simultaneously. Cell viability assay, DNA fragmentation, western blotting, electrophoretic mobility shift assay (EMSA) and multiple modalities of molecular imaging were used to assess the combination efficacy and mechanism of sorafenib and SAHA. The administration of high-dose SAHA (10 µM) with long treatment time (48 h) in vitro, and 25 mg/kg/day by gavage in HCC-bearing nude mice to induce NF-κB activity were performed. Sorafenib inhibited SAHA-induced NF-κB activity and the expression of NF-κB-regulated effector proteins while it increased the efficacy of SAHA against HCC both in vitro and in vivo. The mechanism of sorafenib to enhance SAHA efficacy on HCC is through the suppression of ERK/NF-κB pathway, which induces extrinsic and intrinsic apoptosis. Combination of sorafenib and SAHA may have the potential as new strategy against HCC.

Non-small cell lung cancer (NSCLC) is a malignant lung cancer type with poor prognosis. NF-κB, the oncogenic transcription factor, has been recognized as an important mediator in progression of NSCLC. Regorafenib, a multikinase inhibitor, was demonstrated to inhibit tumor progression through suppression of ERK/NF-κB signaling in hepatocellular carcinoma cells in vitro and in vivo. However, whether regorafenib inhibit progression of NSCLC is ambiguous. Thus, the major purpose of present study was to evaluate anticancer efficacy and underlying mechanism of regorafenib on tumor progression in NSCLC in vitro and in vivo. CL-1-5-F4 cells were treated with regorafenib, NF-κB (QNZ) or AKT (LY294002) inhibitor for 24 or 48 h. Then, we performed cell viability assay, NF-κB reporter gene assay, transwell invasion assay and apoptosis related flow cytometry assay on cellular level to verify anti-cancer effect and mechanism of regorafenib. CL-1-5-F4 bearing animal model was treated with vehicle or regorafenib for 28 days. The therapeutic efficacy and mechanism of regorafenib in CL-1-5-F4 bearing animal model were investigated by tumor size evaluation, whole body computer tomography (CT) scan, Haemotoxylin and Eosin (H&E) stain and immunohistochemistry (IHC) stain. Our results demonstrated regorafenib significantly inhibited tumor growth and induced apoptosis through extrinsic/intrinsic pathways in NSCLC in vitro and in vivo. Furthermore, we also found the suppression of AKT/NF-κB signaling was required for regorafenib inhibited expression of progression-related and invasion-related proteins. Our finding indicated apoptosis induction and suppression of AKT/NF-κB signaling were associated with regorafenib-inhibited progression of NSCLC in vitro and in vivo.

Basaloid squamous cell carcinoma is a distinct variant of squamous cell carcinoma, and it is more aggressive and has a poorer prognosis than conventional squamous cell carcinoma. Basaloid squamous cell carcinoma has been reported to arise from many organs, mainly in the upper aerodigestive tract. Herein, the authors present a 77-year- old woman with a basaloid squamous cell carcinoma over her limbal conjunctiva in the OD.

The anticancer effect of curcumin has been widely reported. However, whether curcumin can enhance the radiosensitivity of human oral squamous cell carcinoma (OSCC) remains to be elucidated. The aim of the present study was to evaluate the efficacy of curcumin combined with radiation against OSCC. SAS cells were transfected with the luciferase gene (luc) and named SAS/luc. NF-κB/DNA binding activity, the surviving fraction and NF-κB-regulated effector protein expression were determined by electrophoretic mobility shift assay, clonogenic survival assay and western blotting, respectively. The therapeutic efficacy was evaluated in SAS/luc tumor-bearing mice by caliper measurement and bioluminescence imaging. Curcumin enhanced SAS/luc radiosensitivity through the inhibition of radiation-induced NF-κB activity and expression of effector proteins both in vitro and in vivo. With 4 Gy or greater radiation doses, synergistic effects of curcumin were observed. The combination group (curcumin plus radiation) had significantly better tumor control compared with that of curcumin or radiation alone. No significant body weight change of mice was found throughout the entire study. In conclusion, curcumin is a radiosensitizer against OSCC with negligible toxicity.

This study presents a design of the body contact in an 850 nm Si photodiode (PD) fabricated using standard 0.18-μm CMOS technology, and presents a systematic investigation of its effects on PD performance. This study confirms a good PD performance within 3 V bias and the establishment of the body current by directly measuring the body current, PD capacitance, and photocurrents. The body current from the biasing body contact was designed to eliminate the slow diffusion photocarriers in the substrate and increase bandwidth. The highest responsivity of 1.2 A/W was obtained from the PD without the body current, with biasing in the avalanche region. Adding the body bias increased the optimal bandwidth from 2.51 to 3.11 GHz, but reduced responsivity. However, the operating bias of the Si PD in the avalanche region was high, making it unsuitable for practical applications. While biasing PD at a low 3 V with a coordinated body bias, a bandwidth of 2.46 GHz was obtained with an acceptable responsivity of 0.1 A/W to allow low-voltage operation.

Background: The most common serious complication following acute ischemic stroke is pneumonia, which may increase mortality and worsen clinical outcomes. The purpose of this study was to investigate the predictors of 30-day mortality in patients with pneumonia following acute ischemic stroke. Methods: From June 2006 to May 2011, we retrospectively included 51 patients with pneumonia following acute ischemic stroke. We analyzed the clinical features, microbiologic data, and outcomes. Predictors of 30-day mortality were investigated by univariate and multivariate analysis. Results: The acute ischemic strokes were caused by large-artery atherosclerosis in 37 (72.5%) of the 51 patients. We found that the most common pathogen responsible for poststroke pneumonia was Klebsiella pneumoniae, followed by Pseudomonas aeruginosa and Escherichia coli. Ultimately, 12 patients died of progressive sepsis due to pneumonia after the acute ischemic stroke. The 30-day mortality rate was 23.5%. In the univariate analysis, patients who died within 30 days had higher National Institutes of Health Stroke Scale scores, higher CURB-65 scores, elevated instability of hemodynamic status, and lower Glasgow Coma Scale (GCS) scores. In Cox regression analysis, a GCS score of

Both optical antipodes of the cis-isomers of osmundalactone, a hydroxypyranone natural product and core structure of the angiopterlactones, have been synthesized from acetylfuran in only three steps through a redox cascade utilizing oxidoreductases and transition metal catalysis in a concerted fashion. The key step in this fully catalytic strategy is the enzyme-mediated Achmatowicz reaction via selective furan oxygenation to furnish the pyran core structure.

Efficient asymmetric bio-epoxidation of electron-deficient α,β-unsaturated ketones was realized via a tandem reduction-epoxidation-dehydrogenation cascade, which proceeds in a switchable manner to afford either chiral epoxy ketones or allylic epoxy alcohols with up to >99% yield and >99%ee.

Modular design is an effective design concept and method that adapts to fierce market competition and versatile customer requirement. Solving the key questions in applying modular design method is the important research topic of modern CAD technology. This paper studies the evaluation question of module combination program, and puts forward the evaluation model for CNC machine tool product. Analytic hierarchy process is used as the evaluation algorithm of combination program. The actual evaluation is carried out to verify the model and algorithm.

According to regenerative chatter theory, this paper abstracts the machining process of XXX machine as a mathematical model firstly. The main process is end milling, so this paper abstracts the machine as an end-milling mathematical model, a delay motion equation with 2-DOF. All parameters of this equation can be acquired by modal analysis. Then SIMULINK model is created based on the mathematical model. According to the response characteristics of simulation analysis system, the method of determining threshold of steady area is acquired.

The ripening characteristics and physiology of two guava cultivars, ‘Jen-Ju Bar’ (‘JJB’) and ‘Li-Tzy Bar’ (‘LTB’), were investigated and compared because of their divergent storability. During storage at 20 °C, mature-green ‘LTB’ fruit exhibited ripening behavior typical for a climacteric fruit, including increases in respiration and ethylene production (3.75 mmol CO 2 kg −1 h −1 and 1.37 × 10 3 nmol C 2 H 4 kg −1 h −1 at peak levels, respectively), yellow color development, flesh softening, and volatile production. By contrast, ‘JJB’ is considered a nonclimacteric fruit because it features low and stable rates of respiration (0.61–0.73 mmol CO 2 kg −1 h −1 ) and ethylene production (less than 4 nmol C 2 H 4 kg −1 h −1 ) while retaining its pale-green color and firmness throughout a 20 d observation period. Furthermore, the nonclimacteric nature of ‘JJB’ fruit was revealed through its responses to various levels of applied ethylene, as its respiration rate increased in a concentration-dependent manner. This respiration enhancement occurred only when exogenous ethylene was present and could be evoked repeatedly in the same ‘JJB’ fruit. The ripening characteristics of ‘JJB’ do not result from a defect in ethylene signaling, but instead result from a lack of autocatalytic ethylene synthesis, as propylene ventilation stimulated normal fruit ripening and an upsurge of respiration without a massive endogenous ethylene release. However, a cutting treatment of ‘JJB’ was able to induce stress-responsive ethylene production expected from system 1 ethylene biosynthesis. The finding that 1-aminocyclopropane-1-carboxylic acid (ACC) content and ACC synthase (ACS) activity were significantly lower in ‘JJB’ than in ‘LTB’ fruit after harvest, together with the finding that treatment with ACC (rather than S -adenosyl- l -methionine) led to both fully ripened ‘JJB’ fruit and endogenous ethylene production, strongly suggest that insufficient ACC synthesis, i.e., the reaction catalyzed by ACS, prevents system 2 ethylene biosynthesis in ‘JJB’ guava fruit.

For the modular design in manufacturing paradigm of mass customization (MC), module combination is a complex process. To the study on this problem, this paper put forward a module combination method based on module family model. Based on the module family model and tree-type storage structure, this method used a “most similar module" search algorithm to carry out the module search, and applied analytic hierarchy process(AHP) to construct the hierarchy model for the evaluation of module combination configuration program. This module combination method has some theoretical and practical ignificance.

This paper took a kind of 3-TPT Parallel Machine Tool (PMT) as the object of research, and it mainly researched the measurement method to position coordinates of movable platform in PMT. First the paper introduced the structure of 3-TPT PMT. Then illustrated the device structure and the basic measurement principle for measuring the position coordinates of movable platform. Finally carried on the theoretical analysis to the specific measurement method and established the corresponding mathematics relationship. The measuring device that was presented in this paper had characteristics of direct-viewing measurement relationship, simple structure and low cost etc., and simultaneously the research results of this paper laid a theoretical foundation for improving the movement precision of this PMT and had important practical significance.

Highly ordered TiO 2 nanotube arrays (TNA) have been synthesized by anodization of Ti foils using an established electrochemical process. The parameters such as anodization potentials and durations have been varied to fabricate the specific morphology of TNA. In addition, Pt nanoparticles were deposited on these TNA via microwave irradiation. The photocurrent density–voltage ( J – V ) properties induced by the standard AM 1.5 solar simulator have been characterized using a potentiostat meter. The efficiency of photoelectrocatalytic effect of the large-pore-sized TNA (=120 nm) is found to be higher than those of the TNA in smaller pore sizes (≤100 nm). TNA with smaller pore sizes exhibit lower surface areas, and therefore, inferior photo-current efficiency to those of TNA with larger pore sizes. The low surface area of smaller-pore-sized TNA was resulted from the shorter tube length obtained at smaller anodizing voltages. Deposition of Pt nanoparticles on TNA was successfully accomplished using microwave irradiation technique. An enhanced hydrogen generation rate of 0.613 ml h −1 cm −2 (≅25.0 μmol h −1 cm −2 ) was obtained on these Pt-deposited TNA compared to the 0.313 ml h −1 cm −2 (≅12.8 μmol h −1 cm −2 ) of pristine TNA in a solution of methanol and water (1:1 ratio).

BACKGROUND: The A118G polymorphism of the mu-opioid receptor gene (OPRM1), resulting in the substitution of an amino acid, has been found to be associated with functional effects and response to opioid treatment. The purpose of this study was to assess whether this polymorphism contributes to the variability in response to tramadol/acetaminophen combination tablets (Ultracet) for treating oxaliplatin-induced painful neuropathy. METHODS: A total of 96 patients with adenocarcinoma of the colon or rectum (n = 84), or stomach (n = 12) who had developed oxaliplatin-induced painful neuropathy were enrolled. Ultracet was administered at 1 tablet every 6 hours, and pain was assessed and scored using a visual analog scale (VAS). The OPRM1 A118G polymorphism was examined with a polymerase chain reaction-direct sequencing method. RESULTS: The allelic frequency of variant (118G) allele was 39.6%, and the prevalence of OPRM1-118 AA, AG, and GG genotypes was 31.3% (n = 30), 58.3% (n = 56), and 10.4% (n = 10), respectively. For all patients, the mean pre-treatment and post-treatment VAS scores were 3.1 and 2.1, respectively (P < .001). Patients with AA genotype had a better analgesic effect than those with G allele variants (AG or GG genotypes). Pre-treatment and post-treatment VAS scores for patients with G allele variants were 3.1 and 2.6, respectively; however, for patients with AA genotype, pre-treatment and post-treatment VAS scores were 3.0 and 0.9, respectively (P < .001). The requirement for rescue analgesia was also higher for patients with G allele variants (P = .01). CONCLUSIONS: These data suggest that Ultracet is effective in the management of oxaliplatin-induced painful neuropathy. A118G polymorphism of OPRM1, by altered function of the mu-opioid receptor and consequential analgesic effect on opioid agents, could be a key determinant for decreased response to Ultracet. Cancer 2011;. © 2011 American Cancer Society.

A series of solution-processable electrochromic (EC) aromatic polyamides with bis(triphenylamine)ether (TPAO) units in the backbone were prepared by the phosphorylation polyamidation from a newly synthesized diamine monomer, bis(N-4-aminophenyl-N-4-methoxyphenyl-4-aminophenyl)ether, and various dicarboxylic acids. These polymers were highly soluble in many organic solvents and showed useful levels of thermal stability associated with high glass-transition tempera- tures and high char yields (higher than 50 at 800 � C in nitrogen). The polymer films showed reversible electrochemical oxidation and electrochromism with high contrast ratio in the visible range, which also exhibited moderate coloration efficiency (CE), low switching time, and good stability. Especially, the polya- mides with two electroactive nitrogen centers only showed one- stage oxidative coloring (no intervalence charge-transfer (IV-CT) band was detected), implying the two electrons are simultane- ously removed from the TPAO units on account of the ether-link- age definitely isolated the two redox centers. The mixed-valence (MV) Class I/II/III transition and electrochemistry of the synthe- sized model compounds were investigated for the bridged triar- ylamine system with various NAN distances and intramolecular electron transfer (ET) capability. V C 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 3805-3816, 2011

We have studied the effect of InN deposited over TiO2 nanoparticle (NP) films on the performance of dye-sensitized solar cells (DSSCs) using N3 dye with I - / I 3 - electrolyte. A 10–20% increase in efficiency was observed for InN deposited, N3 sensitized 5–8.5 μm thick TiO2 films as compared to similar non-treated films. The deposition of InN was carried out in the temperature range of 573–723 K organometallic chemical vapor deposition (OMCVD). Spectral shifts and DFT calculations with a model anchoring group (R′COOH) both suggest binding of the N3 dye directly to both InN and the InN/TiO2 sites.

Silicon photodiodes (PDs) of 850-nm-wavelength, in standard 0.18-μm CMOS technology, are systematically presented and discussed in this study. A basic p-n PD can obtain high responsivity of 0.3 A/W and response of 1.6 GHz while biasing in the avalanche process. However, Si PDs from different CMOS foundries would result in different performance due to the different n-/p-well doping profile. A basic p-n PD with body contact can effectively remove the slow diffusion carrier in the Si substrate and demonstrate improved response. Both body contact and deep n-well design in an octagonal PD can improve the performance of basic p-n PD significantly. The response is improved to 8.7 GHz with 0.8 A/W before breakdown. The improvement is due to the block and elimination of slow diffusion carriers in the Si substrate. Finally, Si PD with built-in n-p-n bipolar junction transistor and edge-coupled PD are proposed to further improve responsivity and response.

The aim of the present study was to verify the effects of fluoxetine on dysregulation of apoptosis and invasive potential in human hepatocellular carcinoma (HCC) SK-Hep1 and Hep3B cells. Cells were treated with different concentrations of fluoxetine for different times. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used for testing the effects of fluoxetine on cell viability. The regulation of apoptosis signaling, and anti-apoptotic, proliferation, and metastasis-associated proteins after fluoxetine treatment were assayed by flow cytometry and Western blotting assay. The detection of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-&kappa, B) activation after fluoxetine treatment was performed by NF-&kappa, B reporter gene assay. The results demonstrated that fluoxetine significantly reduced cell viability, cell migration/invasion, NF-&kappa, B, extracellular signal-regulated kinases (ERK) activation, and expression of anti-apoptotic (Cellular FLICE (FADD-like IL-1&beta, converting enzyme)-inhibitory protein (C-FLIP), Myeloid cell leukemia-1 (MCL-1), X-Linked inhibitor of apoptosis protein (XAIP), and Survivin), proliferation (Cyclin-D1), angiogenesis (vascular endothelial growth factor (VEGF)), and metastasis-associated proteins (matrix metalloproteinase-9 (MMP-9)). Fluoxetine also significantly induced apoptosis, unregulated extrinsic (activation of first apoptosis signal protein and ligand (Fas/FasL), and caspase-8) and intrinsic (loss of mitochondrial membrane potential (&Delta, &Psi, m) pathways and increased Bcl-2 homologous antagonist killer (BAK) apoptosis signaling. Taken together, these results demonstrated that fluoxetine induced apoptosis through extrinsic/intrinsic pathways and diminished ERK/NF-&kappa, B-modulated anti-apoptotic and invasive potential in HCC cells in vitro.

Photocatalytic TiO 2 thin films were prepared via an electron beam-induced deposition (EBID) method. The effects of post-calcination treatment on the properties of the prepared TiO 2 thin films were studied. X-ray diffraction (XRD), scanning electron microscope-energy dispersive spectrometry (SEM-EDS), and UV–V is absorption spectrometry were performed to reveal the crystallinity, surface morphology, chemical composition, and light absorbance of the prepared TiO 2 thin films. The photoelectrochemical characteristics of the TiO 2 thin films were investigated with a potentiostat. Under UV irradiation, a photocurrent of ˜2.1 mA was observed for the TiO 2 thin film with post-calcination at 500 °C. A water-splitting reaction was conducted over the TiO 2 thin film with the best photoelectrochemical performance. The yields of hydrogen and oxygen were 59.8 and 30.6 μmole, respectively, after 8 h of reaction under UV irradiation.

In the present study, ITO nanowires electrode within the anodized Ti0 2 nanotubes without using the polycarbonate membrane templates were attempted. The process begins with an anodized Ti0 2 nanotube arrays (TNA) and subsequent growth of indium-tin-oxide (ITO) nanowires into the Ti0 2 annotube arrays via the electrophoretic process (EPD). The open-end of Ti0 2 nanotubes were synthesized for the photoelectrode of DSSC. ITO nanowires were then grown into these TNA by EPD process. The composite of ITO/anodized TNA was employed as the working electrode for the assembly into DSSCs. The advantage of the present method is that the membrane templates in EPD process were not required. In addition, the ITO nanowires will surely not contact each other which might cause short circuit. The morphologies and the structures of ITO nanowires and TNA electrode were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

A newly isolated actinomycete, Gordonia neofelifaecis (NRRL B-59395) from the faeces of Neofelis nebulosa, was used to selectively degrade the side-chain of cholesterol. The intermediates were purified and characterized. Quantitative analysis of the accumulated metabolites from cholesterol side-chain cleavage was conducted during the biotransformation. The results showed that the profile of accumulated intermediates was different from those of other reported microorganisms. Among the five metabolites, androsta-1,4-diene-3,17-dione (ADD) was the main product of the side-chain degradation, with a high conversion rate (87.2%), indicating its potential for industrial production of ADD. At the end of transformation, the substrate cholesterol was completely consumed. The effect of some factors on the bioconversion was also investigated. To our best knowledge, this is the first report regarding cholesterol side-chain cleavage using bacteria belonging to Gordonia.

The mechanism and kinetics of the reaction CF3CH2OCHO + Cl are investigated theoretically by using a dual-level direct dynamics method. The geometries and frequencies are calculated at the B3LYP/6-311G(d,p), B3LYP/6-311+G(d,p), and MP2/6-31G(d,p) levels, and high-level single-point energy calculations are performed at the BMC-CCSD level. It is shown that the reaction proceeds exclusively via two hydrogen abstraction channels, while the Cl addition–elimination channel is unfavorable. Furthermore, the rate constants of the two H-abstraction channels are evaluated by means of canonical variational transition-state theory (CVT) with the small-curvature tunneling (SCT) correction over a temperature range of 200–1000 K. The overall rate constant at room temperature is in good agreement with the experimental value. This study show that the formyl-H-abstraction channel is the major reaction pathway at low temperatures, while as the temperature increases, methylene-H-abstraction channel becomes more important and competes with the former. The three parameter rate-temperature expression is fitted to be k = 0.17 × 10−20 T3.13exp(−23.9/T) cm3 molecule−1 s−1 (200–1000 K). The present study may assist in further laboratory work.

In Taiwan, where Mandarin is the official language, the survival of Taiwanese, the mother tongue of sixty percent of the island’s inhabitants, is threatened. In this article, the authors discuss data from previous and ongoing research on the role of language and the significance of language loss in the quest for a “Taiwanese identity.” Research shows that the dominance of Mandarin over Taiwanese plus the growing support for English in Taiwan are likely indications that current Mandarin/Taiwanese bilingualism is being replaced by Mandarin/English bilingualism. Canadian, Finnish, Basque and Catalonian models of language immersion programs will be proposed as an alternative to Taiwan’s current language policy. The authors argue that such models, when applied to a significant degree in Taiwan’s primary education system, will contribute to strengthening Taiwanese identity, to defending the right of youngsters to receive their education in their Taiwanese mother tongue, and to creating more effective English language training., Le mandarin, langue officielle de Taiwan, menace la survie du taiwanais, qui est la langue maternelle de soixante pour cent de la population de l’île. Dans le présent article, les auteurs discutent des résultats de leurs recherches précédentes et en cours et montrent la signifiance de la perte de la langue maternelle pour l’identité taiwanaise. Ils montrent également que la suprématie du mandarin sur le taiwanais et l’appui croissant en faveur de l’anglais à Taiwan laissent prévoir l’implantation d’un bilinguisme mandarin/anglais au détriment du bilinguisme mandarin/taiwanais. Les auteurs considèrent que les modèles d’enseignement bilingue immersif mis en place au Canada, en Finlande, dans le pays Basque et en Catalogne, s’ils étaient mis en oeuvre de façon généralisée à Taiwan, pourraient contribuer à renforcer l’identité taiwanaise, à défendre le droit des jeunes à une éducation dans leur langue maternelle et à favoriser l’enseignement plus efficace de l’anglais.

Styrene monooxygenases (SMOs) can catalyze the asymmetric epoxidation of alkenes to obtain optically active epoxides. This account describes a series of work of our group on the isolation, application, and improvement of an SMO from Pseudomonas sp. LQ26. The strain was isolated from an active sludge sample based on indigo-forming capacity. Then the gene encoding SMO was expressed in Escherichia coli, and the whole cells were applied in biocatalytic reactions. The substrate spectrum of SMO was successfully expanded from conjugated styrene derivatives to non-conjugated alkenes, especially α-substituted secondary allylic alcohols, affording enantiopure epoxides. Most significantly, cascade reactions involving ketoreductase and SMO were designed, which resulted in glycidol derivatives or epoxy ketones with excellent enantio- and diastereo-selectivity using α,β-unsaturated ketones as the substrates. In addition, mutants of SMO with altered substrate preference and enhanced activity were constructed, which indicated great potential of SMO for further improvement.

This paper presents data from a quantitative survey based on 746 written questionnaires and 23 semi-structured interviews. The main purpose of the study was to measure Southern Min and Mandarin lower domain language use among a cross-section of Taiwan’s multilingual population. As organizing elements for our discussion of Taiwan’s current language situation, we made use of Sridhar’s notion of societal multilingualism as well as Ó Riagáin’s idea that the home is possibly the first domain to exhibit language shift. This study followed Ó Riagáin by focusing our research on lower domain language use as well as relevant political determinants. We investigated whether Southern Min speakers tend to prefer a Taiwanese rather than Chinese identity, and whether the Taiwanese link their language choice to age, gender, and region of origin. Political improvements in Taiwan for the past two decades did enable the Taiwanese to compete with the Mainlanders who moved to Taiwan and they now have a stronger case to promote the status of Southern Min and maintain it. Evidence of language shift was discovered: proficiency in Mandarin by the Taiwanese is increasing, while that in Southern Min is decreasing. It is predicted that this language shift will continue, but that the attitudes held by Taiwanese toward their ethnic identity might slow down such a process considerably.

The aim of the present study was to investigate whether amentoflavone induces anti-angiogenic and anti-metastatic effects through suppression of NF-κB activation in breast cancer in vitro. Effects of NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4, 6-diamine (QNZ) and amentoflavone on the expression and secretion of angiogenesis- and metastasis-related proteins and cell invasion were investigated by western blotting, enzyme-linked immunosorbent assay (ELISA), and invasion assays. We also verified the effects of QNZ and amentoflavone on lipopolysaccharides (LPS)-activated cell invasion. Obtained results indicated that both QNZ and amentoflavone reduce NF-κB activation, expression and secretion of angiogenesis- and metastasis-related proteins, and cell invasion. QNZ and amentoflavone also reverse LPS-activated cell invasion. In conclusion, inhibition of NF-κB activation decreases expression and secretion of angiogenesis- and metastasis-related proteins. Amentoflavone may induce anti-angiogenic and anti-metastatic effects through suppression of NF-κB activation.

Oral squamous cell carcinoma often causes bone invasion resulting in poor prognosis and affects the quality of life for patients. Herein, we combined radiation with sorafenib, to evaluate the combination effect on tumor progression and bone erosion in an in situ human OSCC-bearing mouse model. Treatment procedure were arranged as following groups: (a) normal (no tumor); (b) control (with tumor); (c) sorafenib (10 mg/kg/day); (d) radiation (single dose of 6 Gy); (e) pretreatment (sorafenib treatment for 3 days prior to radiation) and (f) concurrent treatment (sorafenib and radiation on the same day). The inhibition of tumor growth and expression level of p65 of NF-κB in tumor tissues were the most significant in the pretreatment group. EMSA and Western blot showed that DNA/NF-κB activity and the expressions of NF-κB-associated proteins were down-regulated. Notably, little to no damage in mandibles and zygomas of mice treated with combination of sorafenib and radiation was found by micro-CT imaging. In conclusion, sorafenib combined with radiation suppresses radiation-induced NF-κB activity and its downstream proteins, which contribute to radioresistance and tumorigenesis. Additionally, bone destruction is also diminished, suggesting that combination treatment could be a potential strategy against human OSCC.

Styrene monooxygenase (SMO) can catalyze the kinetic resolution of secondary allylic alcohols to provide enantiopure glycidol derivatives. To overcome the low theoretical yield of kinetic resolution, we designed a one-pot two-step enzymatic cascade using prochiral α,β-unsaturated ketones as the substrates. An S-specific ketoreductase ChKRED03 was screened for the efficient bioreduction of the substrates to provide (S)-allylic alcohols, which underwent SMO-catalyzed epoxidation to achieve glycidol derivatives with contiguous stereogenic centers. Excellent enantioselectivity (ee > 99%) and diastereoselectivity (de > 99%) were achieved for the majority of the substrates, and product yields reached up to >99%.

Treatment for non-small-cell lung cancer with gefitinib and erlotinib is efficacious. However, while many studies have reported on gefitinib-related interstitial lung disease (ILD), less published data are available regarding erlotinib-induced ILD. Here, we report a case of pulmonary adenocarcinoma who developed ILD due to gefitinib initially and erlotinib thereafter. The two episodes of ILD were treated successfully with the discontinuation of the tyrosine kinase inhibitors and high-dose intravenous corticosteroids.