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The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABA(A) receptor. This effect of myricetin was not blocked by the GABA(A) receptor benzodiazepine- (BZ-) binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca(2+)/calmodulin-stimulated protein kinase II (CaMK-II). Patch clamp and live Ca(2+) imaging studies found that myricetin could increase Ca(2+) current and intracellular Ca(2+) concentration, respectively, via T- and L-type Ca(2+) channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances GABA(A) receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABA(A) receptor.

We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families.

Aims In the present study, we determined whether Phosphoinositide 3-kinase (PI3K) and Notch signal pathways are involved in the expression of cyclinD1, cyclinA and p27kip1 which were key molecules in controlling cell cycling from CD4+ T lymphocyte in animal model of asthma. Main methods Ovalbumin (OVA) sensitized murine model of asthma was used to investigate the expression of cyclin D1, cyclin A, and p27kip1 by splenic CD4+ T lymphocytes. We further observed the effect of specific inhibitor of PI3K(LY294002) and specific inhibitor of Notch(DAPT) on the proliferation of such CD4+ T lymphocytes. Key findings We found that the expression of cyclinD1 and cyclinA was upregulated at both protein and mRNA levels in asthma group while p27kip1 was down-regulated. Both LY294002 and DAPT inhibit the proliferation of CD4+ T lymphocytes in a time- and dose-dependent manner. Furthermore, LY294002 and DAPT have additive effect in down-regulation of cyclinD1 and upregulation of p27kip1. An upregulation of cyclinA, although not statistically significant, was also observed. Significance These data suggested that PI3K signal pathway and Notch signal pathway may coordinately regulate the cell proliferation and differentiation processes through up-regulating cyclinD1 and down-regulating p27kip1 of CD4+ T lymphocytes.

Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T-T.G. and Q-J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case–control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case–control studies were 0.89 (95% CI = 0.76–1.03) and 0.84 (95% CI = 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta-analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.

Summary Aim To investigate the mechanism of endoplasmic reticulum (ER) stress–induced apoptosis as well as the protective action of basic fibroblast growth factor (bFGF) both in vivo and in vitro. Methods and Results ER stress–induced apoptosis was involved in the injuries of spinal cord injury (SCI) model rat. bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase-12, which are ER stress–induced apoptosis response proteins. bFGF administration also increased the survival of neurons and the expression of growth-associated protein 43 (GAP43), which is related to neural regeneration. The protective effect of bFGF is related to the activation of downstream signals, PI3K/Akt/GSK-3β and ERK1/2, especially in the ER stress cell model. Conclusions This is the first study to illustrate that the role of bFGF in SCI recovery is related to the inhibition of ER stress–induced cell death via the activation of downstream signals. Our work also suggested a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress–induced apoptosis.

Background The ubiquitin-proteasome system and macroautophagy (hereafter referred to autophagy) are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy. Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired. Method Autophagy activation was measured using acridine orange staining and LC3 transition. Cell viability and apoptosis were measured using MTT assay and flow cytometry, respectively. Beclin 1 expression vectors or shRNA against Beclin 1 (shBeclin 1) were transfected to investigate the role of Beclin 1 in autophagy activation and cytotoxicity of ovarian cancer cells induced by proteasome inhibitors. Results Proteasome inhibitors suppressed proliferation and induced autophagy in ovarian cancer cells. Neither phosphoinositide 3-kinase (PI3K) inhibitors nor shRNA against Beclin 1 could abolish the formation of acidic vacuoles and the processing of LC3 induced by proteasome inhibitors. Moreover, Beclin 1 overexpression enhanced anti-proliferative effects of proteasome inhibitors in ovarian cancer cells. Conclusions For the first time, the current study demonstrated that proteasome inhibitors induced PI3K and Beclin 1-independent autophagy in ovarian cancer cells. In addition, this study revealed autophagy-independent tumor suppressive effects of Beclin 1 in ovarian cancer cells.

Distortion discriminated criteria play a very important role in rate-distortion optimization (RDO), which is an effective way of video encoding. In x264, the sum of the square differences (SSD) and the sum of the absolute differences (SAD) are used as quality metrics for RDO, while these two criteria are poorly correlated to human visual system. In this paper, the structural similarity index (SSIM) is used in the RDO scheme and an improved algorithm based on hybrid distortion discriminated criteria is proposed for x264 intra mode selection. With plenty of simulations, the RDO formula with SSIM is remodeled. The results show that the proposed method can provide better subject visual quality of the reconstructed video than the original x264.

The objective of this study was to examine the expression levels of RE1-silencing transcription factor (REST) and class III β-tubulin (TUBB3) in ovarian cancer and to determine if there is a correlation between their expression and resistance to chemotherapy in ovarian cancer. The protein expression of REST and TUBB3 in ovarian cancer was detected by Western blot analysis. REST expression was inhibited by small interfering ribonucleic acid (siRNA) in human ovarian cancer cell lines. The levels of REST and TUBB3 protein expression were detected by immunohistochemistry. The relationship between REST and TUBB3 expression and chemotherapy resistance, clinicopathological parameters, and prognosis of ovarian cancer was then determined. The present study found that REST was more highly expressed in the ovarian SKOV3 carcinoma cell line compared to the paclitaxel-resistant ovarian cancer cell line, SKOV3/TAX (P = 0.01). In contrast, TUBB3 was more highly expressed in SKOV3/TAX cells compared to SKOV3 cells (P = 0.01). After REST siRNA interference, TUBB3 expression increased in SKOV3 cells. REST expression was significantly higher in the paclitaxel-sensitive group compared to the paclitaxel-resistant group (70.7 % vs. 37.0 %, P0.05). However, TUBB3 expression was significantly lower in the paclitaxel-sensitive group compared to the paclitaxel-resistant group (47.6 % vs. 77.8 %, P0.05). Notably, REST was more highly expressed in TUBB3-negative cases than TUBB3-positive cases (P0.05). Univariate analyses indicated that both REST and TUBB3 expression were unrelated to tumor differentiation, histological type, and clinical stage (all P0.05). According to the Cox regression model, negative REST and positive TUBB3 protein expression was detected as independent prognostic factors (P = 0.003 and P = 0.005, respectively). REST and TUBB3 protein may be potential biomarkers for chemoresistance and prognosis in ovarian cancer.

To evaluate the efficacy of integrated comparative omics in screening candidate biological macromolecules, three methods, namely, 2-DE + MALDI-TOF-MS, tumor-associated cDNA microarray and whole-transcriptome cDNA microarray were examined by three biotechnological companies to compare a stable transfected cell line with its control one. The results showed that the percentages of the up-regulate in three methods are largely consistent. 21.59 % of tumor-associated microarray results are the same with that of whole-transcriptome microarray. SOD2 is the unique intersection of three methods. Consulting the results of pI and Mw derived from microarray cannot increase the detection rate of target molecules during protein spot selection for mass spectrometry. Two protein spots with different regulating directions were identified to be the same protein. Conclusively, proteomic and genomic methods reveal the macromolecular changes from different aspects. Their detection ranges are complementary. The combination of different genomic methods can improve the validity and stability and reduce the noise changes. However, it is no sense to compare proteomics with genomics.

Objective: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells. Methods: mRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the α1,2-fucosyltransferase gene by real-time PCR, and protein levels of cyclins, CDKs and CKIs were determined in cells before and after gene transfection by Western blot. Results: Lewis y overexpression led to an increase in both mRNA and protein expression levels of cyclin A, cyclin D1 and cyclin E in ovarian cancer cells, decrease in both mRNA and protein expression levels of p16 and p21, and decrease of p27 at only the protein expression level without change in its mRNA level. There were no differences in proteins and the mRNA levels of CDK2, CDK4 and CDK6 before and after gene transfection. Anti-Lewis y antibody, ERK and PI3K pathway inhibitors PD98059 and LY294002 reduced the difference in cyclin and CKI expression caused by Lewis y overexpression. Conclusion: Lewis y regulates the expression of cell cycle-related factors through ERK/MAPK and PI3K/Akt signaling pathways to promote cell proliferation.

The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABAA receptor. This effect of myricetin was not blocked by the GABAA receptor benzodiazepine- (BZ-) binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca2+/calmodulin-stimulated protein kinase II (CaMK-II). Patch clamp and live Ca2+ imaging studies found that myricetin could increase Ca2+ current and intracellular Ca2+ concentration, respectively, via T- and L-type Ca2+ channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances GABAA receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABAA receptor.

The aim of this study was to investigate the detection rate and methods of micrometastases in early-stage cervical cancer by detecting the expression of high-risk HPV DNA and CK19 in pelvic lymph nodes. A total of 104 lymph nodes with/without pathologically confirmed metastases, from 28 patients with early-stage cervical cancer, were included for detection of high-risk HPV DNA and CK19 expression using in situ hybridization and immunohistochemistry, respectively. The detection rate of high-risk HPV DNA and CK19 in lymph nodes in patients with pathologically-confirmed lymph node metastases was higher compared to that in lymph nodes in patients without pathologically-confirmed lymph node metastases (P

Epithelial carcinomas of the ovary exhibit the highest mortality rate among gynecologic malignancies. Studies found that the metabolism of glycolipids or carbohydrates is associated with acquirement of anticancer drug-resistance by cancer cells. This study was to characterize possible involvement of Lewis Y (Le(Y)) antigen in the drug-resistance of cancer cells. We transfected the α1,2-fucosyltransferase gene into human ovarian carcinoma-derived RMG-1 cells and established RMG-1-hFUT cells with enhanced expression of Le(Y). We determined the effects of docetaxel on the survival of cells by MTT assaying and observed the apoptosis of cells in the presence of docetaxel by flow cytometric analysis and by transmission electron microscopy. Plasma membranes and intracellular granules in RMG-1-hFUT cells were stained with anti-Le(Y) antibody, the intensity of the staining was higher than that in control cells. The RMG-1-hFUT cells exhibited higher resistance to docetaxel than the control cells with regard to the docetaxel concentration and time course. After treatment with 10 μg/mL docetaxel for 72 h, the control cells, but not RMG-1-hFUT, contained abundant positively stained cell debris due to disintegration of the cytoskeleton. On transmission electron microscopy, although the control cells treated with docetaxel as above showed the following morphology, i.e., absence of villi, cells shrunken in size, pyknosis, agglutinated chromatin and cell buds containing nuclei in the process of apoptosis, the RMG-1-hFUT cells showed only agglutinated chromatin and vacuoles in the cytoplasm. In summary, cells with enhanced expression of Le(Y) were shown to acquire docetaxel-resistance, indicating the possible involvement of glycoconjugates in the drug-resistance.

Lewis y is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of Lewis y is frequently observed in epithelial-derived cancers. This study aimed to detect the expression and clinical significance of the Lewis y antigen and TGF-β1 (transforming growth factor β1) in ovarian epithelial tumors, and to evaluate the correlation between them. Immunohistochemical staining was used to detect the expression of Lewis y antigen and TGF-β1 in 60 cases of ovarian epithelial malignant tumors, 20 cases of borderline ovary tumors, 20 cases of benign ovary tumors and 10 cases of normal ovarian tissues. An immunofluorescence double labeling method was also used to detect the correlation between Lewis y antigen and TGF-β1. The positive rates of Lewis y antigen in ovarian epithelial cancer tissues was 88.33%, significantly higher compared to those of borderline ovarian tumors (60.00%) (P0.05). Expression of Lewis y antigen and TGF-β1 was significantly positively associated with epithelial carcinoma. Close correlation between Lewis y, TGF-β1 and ovarian cancer was observed. Altered expression of Lewis y antigen may cause changes in TGF-β1 expression. Lewis y can increase the growth of ovarian cancer cells and the invasion ability by promoting TGF-β1 abnormal expression and by promoting angiogenesis and a change in its signal transduction pathway. This study provides theoretical evidence for the development of ovarian cancer biological treatments.

Objective: To detect the expression and clinical significances of Lewis y antigen and integrin αv, β3 in epithelial ovarian tumors, and to explore the expression correlation between Lewis y antigen and integrin αv, β3. Methods: Immunohistochemical staining was performed in 95 cases of epithelial ovarian cancer, 37 cases of borderline tumors, 20 cases of benign tumors, and 20 cases of normal ovarian tissue, for the detection of Lewis y antigen and integrin αv, β3 expressions, and to analyze the relationship between Lewis y antigen and integrin, and the relationship between clinical and pathological parameters of ovarian cancer. In addition, immunofluorescence double labeling was utilized to detect the expression correlation between Lewis y antigen and integrin αv, β3 in ovarian cancer. Results: In epithelial ovarian tumors, the expression rate of Lewis y antigen was 81.05%, significantly higher than that of borderline (51.53%) (P < 0.05) and benign (25%) (P < 0.01) tumors, and normal ovarian tissues (0) (P < 0.01). The expression rate of integrin αv, β3 in malignant epithelial ovarian tumors was 78.95% and 82.11%, respectively, significantly higher than that of the borderline (45.94%, 40.54%) (both P < 0.05), benign group (10.00%, 15.00%) (both P < 0.01) and normal ovary group (5%, 15%) (both P < 0.01). Conclusions: Lewis y and integrins αv, β3 are relevant to pelvic and abdominal diffusion and metastasis of ovarian cancer cells, suggesting that these two molecules mediate a boosting function for tumor metastasis.

Background This study aimed to investigate the molecular structural relationship between cell adhesive molecule CD44 and Lewis y antigen, and determine the effects of Lewis y antigen on CD44-mediated adhesion and spreading of ovarian cancer cell line RMG-I and the Lewis y antigen-overexpressed cell line RMG-I-H. Methods The expression of CD44 in RMG-I and RMG-I-H cells before and after treatment of Lewis y monoclonal antibody was detected by immunocytochemistry; the expression of Lewis y antigen and CD44 was detected by Western Blot. The structural relationship between Lewis y antigen and CD44 was determined by immunoprecipitation and confocal laser scanning microscopy. The adhesion and spreading of RMG-I and RMG-I-H cells on hyaluronic acid (HA) were observed. The expression of CD44 mRNA in RMG-I and RMG-I-H cells was detected by real-time RT-PCR. Results Immunocytochemistry revealed that the expression of CD44 was significantly higher in RMG-I-H cells than in RMG-I cells (P < 0.01), and its expression in both cell lines was significantly decreased after treatment of Lewis y monoclonal antibody (both P < 0.01). Western Blot confirmed that the content of CD44 in RMG-I-H cells was 1.46 times of that in RMG-I cells. The co-location of Lewis y antigen and CD44 was confirmed by co-immunoprecipitation. The co-expression of CD44 and Lewis y antigen in RMG-I-H cells was 2.24 times of that in RMG-I cells. The adhesion and spreading of RMG-I-H cells on HA were significantly enhanced as compared to those of RMG-I cells (P < 0.01), and this enhancement was inhibited by Lewis y monoclonal antibody (P < 0.01). The mRNA level of CD44 in both cell lines was similar (P > 0.05). Conclusion Lewis y antigen strengthens CD44-mediated adhesion and spreading of ovarian cancer cells.

Researches on third-party logistics have become increasingly fruitful, so it's very urgent to evaluate the service quality of third-party logistics reasonably. This paper establishes a service quality evaluation model of third-party logistics based on the SERVQUAL quality evaluation system, and evaluates the service quality of third-party logistics reasonably with dynamic fuzzy comprehensive evaluation method. The results show that dynamic fuzzy method can accurately reflect where the failure of third party logistics services is, and give forecasts. Finally, the validity of the model is verified by an example.

The fresh food logistics outsourcing quality supervision is analyzed by using the game theory. Based on different hypothesis models of one-stage game and multi-stage games are established. And the equilibrium strategy for the two parties is produced. Some key factors impact on the two parties. Some factors like the supervision cost of the fresh food enterprises and the cheat amount for the third party company are discussed. Then the paper suggests that fresh food enterprises reduce the risks or the quality problems of the logistics outsourcing.

This study investigates the expression and the clinical significance of Lewis y and integrins α5 and β1 in serous and mucinous ovarian tumors and then evaluates the association between them.Lewis y and integrin α5 and β1 expression are detected on tissues from malignant, borderline, and benign ovarian serous and mucinous tumors and normal tissues. Their expression and relationship are assessed in paraffin sections using immunohistochemistry and double-labeling immunofluorescence method.Lewis y was mainly expressed in ovarian serous and mucinous cancers (88.33%); its positive rate was obviously higher than rates in the borderline (60.00%, P0.05) and benign ovarian tumors (35.00%, P0.01) and normal ovarian tissues (0, P0.01) and was not associated with clinicopathological characteristics. Integrins α5 (85.00%) and β1 (81.67%) were also mainly expressed in ovarian serous and mucinous cancers; their positive rates were all obviously higher than those in benign ovarian tumors (60.00% and 55.00%, respectively; all P0.05) and normal tissues (40.00% and 30.00%, respectively; all P0.01). Increased expression of integrins α5 and β1 correlated with higher clinical stage (P0.05) but were not associated with histological types, differentiation degree, and lymphatic metastasis (P0.05). The expression intensity of Lewis y and integrins α5 and β1 was significant with clinical stage and differentiation degree (all P0.05) in ovarian cancer; positive significant correlation between Lewis y antigen and integrins α5 and β1 was observed in serous and mucinous ovarian cancer tissues.A close correlation between Lewis y, integrins α5 and β1, and ovarian cancer was observed. Lewis y can influence the biological behavior of a tumor cell as an important composition of integrins α5 and β1 by some signal pathway, such as promoting cell adhesion and migration, and this study provides theoretical evidence of ovarian cancer biological treatment.

Lewis (y) antigen, a difucosylated oligosaccharide, has been shown to be associated with malignant properties of ovarian carcinomas. In this study, we have investigated the potential role of Lewis (y) antigen, which was stably transfected into ovarian cancer RMG-1 cells, on carboplatin-induced apoptosis. Overexpression of Lewis (y) antigen effectively protected vitronectin-adherent RMG-1 cells from carboplatin-induced apoptosis as assessed by Hoechst 33258 staining and flow cytometry. Treatment with anti-Lewis (y) antigen, anti-integrin αv, or anti-integrin β3 antibody partially abolished the protective effect on apoptosis and markedly inhibited the expression of Topo-II β in cells overexpressing Lewis (y) antigen (all P0.01). Moreover, elevated expression of Topo-I and Topo-II β was found in Lewis (y) antigen-overexpressing cells (P0.01). However, no obvious changes in Topo-II α were observed throughout the study (P0.05). Taken together, these data suggest that the overexpression of Lewis (y) antigen confers cell adhesion-mediated drug resistance to apoptosis in ovarian cancer cells by the upregulation of Topo-I and Topo-II β. Therefore, the inhibition of Lewis (y) antigen may be a novel strategy of cancer chemotherapy.

Improving stress tolerance of the microbial producers is of great importance for the process economy and efficiency of bioenergy production. Key genes influencing ethanol tolerance of brewing yeast can be revealed by studies on the molecular mechanisms which can lead to the further metabolic engineering manipulations for the improvement of ethanol tolerance and ethanol productivity. Trahalose shows protective effect on the cell viability of yeast against multiple environmental stress factors, however, further research is needed for the exploration of the underlying molecular mechanisms. In this study, the promoter region of the trehalose-6-phosphate synthase gene TPS1 was cloned from the self-flocculating yeast Saccharomyces cerevisiae flo, and a reporter plasmid based on the expression vector pYES2.0 on which the green fluorescence protein EGFP was directed by the TPS1 promoter was constructed and transformed to industrial yeast strain Saccharomyces cerevisiae ATCC4126. Analysis of the EGFP expression of the yeast transformants in presence of 7% and 10% ethanol revealed that the P(TPS1) activity was strongly induced by 7% ethanol, showing specific response to ethanol stress. The results of this study indicate that trehalose biosynthesis in self-flocculating yeast is a protective response against ethanol stress.

In this paper, a surveillance system which provides the protection for property in public places is proposed. Firstly, aiming at the problem of small visual field, Omni-Directional Vision Sensors (ODVS) which has 360 degree and non-dead-angle view is used to capture panoramic images of scene. Secondly, two backgrounds are constructed for detecting a temporarily stationary object, which one is short-term and another is long-term. At last, find out the real thief among the people in the scene and capture the details of it.

In order to adapt to the development of food enterprises, that more and more logistics operations will be outsourced by food companies increasingly. So to manage the risks become one of the most important issues. In order to control the risk of logistics outsourcing better, so that this paper analyzes food enterprises’ risk of logistics outsourcing, then use the method–fuzzy evaluation to construct the assessment model based on qualitative analysis and quantify uncertainty acossing logistics out souring. It is good for analysis the size of logistics outsourcing which will good for food enterprises to control the business of logistics outsoucing with the under the disposed to quantify food enterprises’ risk of logistics outsourcing.

Blood pressure reduction is an important and effective strategy in stroke prevention in hypertensives. Recently, we found that baroreflex restoration was also crucial in stroke prevention. The present work was designed to test the hypothesis that a combination of blood pressure reduction and baroreflex restoration may be a new strategy for stroke prevention. In Experiment 1, the effects of ketanserin (0.3, 1, 3, 10 mg/kg), amlodipine (0.3, 1, 2, 3 mg/kg) and their combination (1 + 0.3, 1 + 1, 1 + 2, 1 + 3 mg/kg) on blood pressure and baroreflex sensitivity (BRS) of stroke-prone spontaneously hypertensive rats (SHR-SP) were determined under conscious state. It was found that both amlodipine and ketanserin decreased blood pressure dose-dependently. Ketanserin enfanced BRS from a very small dose but amlodipine enfanced BRS only at largest dose used. At the dose of 1 + 2 mg/kg (ketanserin + amlodipine), the combination possessed the largest synergism on blood pressure reduction. In Experiments 2 and 3, SHR-SP and two-kidney, two-clip (2K2C) renovascular hypertensive rats received life-long treatments with ketanserin (1 mg/kg) and amlodipine (2 mg/kg) or their combination (0.5 + 1, 1 + 2, 2 + 4 mg/kg). The survival time was recorded and the brain lesion was examined. It was found that all kinds of treatments prolonged the survival time of SHR-SP and 2K2C rats. The combination possessed a significantly better effect on stroke prevention than mono-therapies. In conclusion, combination of blood pressure reduction and baroreflex restoration may be a new strategy for the prevention of stroke in hypertension.

Lewis(y) antigen is an oligosaccharide containing two fucoses, and is expressed variously in 75% of ovarian tumors, where its high expression level predicts poor prognosis. The effect and the possible mechanism of Lewis(y) on the proliferation of human ovarian cancer cells are still largely unkown. We report here that transfecting alpha1,2-FT gene into RMG-I cells increased the expression of Lewis(y) and promoted cell proliferation. In alpha1,2-FT-transfected cells, the Lewis(y) content of EGFR was increased dramatically. Tyrosine phosphorylation of EGFR was elevated. Concomitantly, tyrosine phosphorylation of Akt, ERK1/2 was also upregulated. Moreover, the expression of HER2/neu mRNA and protein, the tyrosine phosphorylation of HER2/ neu were also elveated, while the expression of p27 was significantly reduced. However, the expression of EGFR and the relative content of Lewis(y) on HER2/neu were unchanged. The above-mentioned alterations were correlated with the Lewis(y) content of EGFR and alpha1,2-FT expression in cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of alpha1,2-FT were attenuated significantly by the inhibitor of EGFR tyrosine kinase and by the mono-antibody to Lewis(y). Meanwhile, the reduction in p27 and the difference in its expression among the two cell lines were also blocked by the Lewis(y) antibody. The PI3K signaling pathway was more important than the MAPK pathway in the regulation of p27 expression. These findings provide strong evidence that increased expression of Lewis(y) promotes cell proliferation through regulating the phosphorylation and expression of some molecules involved in the EGFR/PI3K-signaling pathway.

The paper points out the supply chain with one manufacturer and two markets. The strategies of adding price and discriminate price are adopted for manufacturer in order to make the profit maximize. Compared to the normal price strategy, the maximum profit is obtained for manufacturer which the two price strategies are adopted for the two markets at the same time. Finally, a numerical example is given to illustrate the effectiveness of price strategy for promoting and profit of supply chain.

The coordination problem of a supply chain with one supplier and one retailer is analyzed under the condition that the cost information of the retailer is asymmetric. A revenue-sharing contract model is established, in the model, the supplier have the decision-making power of wholesale price and revenue sharing ratio, and the retailer have the decision-making power of hiding the information of marginal cost and confirming order quantity and retail price. The coordination mechanism issue of both the centralized supply chain and the decentralized supply chain under symmetric information is analyzed respectively. Meanwhile, based on that the cost information of the retailer is asymmetric, an incentive mechanism is established in order to prevent the retailer from providing false cost information and increase their profit under optimizing the profit of the supply chain.

BackgroundLewis y antigen is difucosylated oligosaccharide and is carried by glycoconjugates at cell surface. Elevated expression of Lewis y has been found in 75% of ovarian tumor, and the high expression level is correlated to the tumor's pathological staging and prognosis. This study was to investigate the effect and the possible mechanism of Lewis y on the proliferation of human ovarian cancer cells.MethodsWe constructed a plasmid encoding α1,2-fucosyltransferase (α1,2-FT) gene and then transfected it into ovarian carcinoma-derived RMG-I cells with lowest Lewis y antigen expression level. Effect of Lewis y on cell proliferation was assessed after transfection. Changes in cell survival and signal transduction were evaluated after α-L-fucosidase, anti-Lewis y antibody and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.ResultsOur results showed that the levels of α1,2-FT gene and Lewis y increased significantly after transfection. The cell proliferation of ovarian carcinoma-derived RMG-I cells sped up as the Lewis y antigen was increased. Both of α-L-fucosidase and anti-Lewis y antibody inhibited the cell proliferation. The phosphorylation level of Akt was apparently elevated in Lewis y-overexpressing cells and the inhibitor of PI3K, LY294002, dramatically inhibited the growth of Lewis y-overexpressing cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of α1,2-FT were attenuated significantly by the monoantibody to Lewis y and by the PI3K inhibitor LY294002.ConclusionsIncreased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.

Le(Y) antigen is known to be associated with malignant properties including metastasis and a poor prognosis of ovarian carcinomas. To clarify the mechanisms underling these properties, we established ovarian carcinoma-derived cells exhibiting enhanced expression of Le(Y) by transfection with alpha1,2-fucosyltransferase and compared their cellular properties with those of the original cells. So the human alpha1,2-fucosyltransferase gene was transfected into ovarian carcinoma-derived RMG-1 cells, which are known to contain Le(X), a precursor of Le(Y), and RMG-1-hFUT cells exhibiting enhanced expression of Le(Y) were established by selection with anti-Le(Y) antibodies, and their adhesive and spreading potentials on fibronectin-coated plates were compared with those of RMG-1 cells. Results showed that the relative expression of Le(Y) in RMG-1-hFUT cells was about 20-fold that in RMG-1 cells, and that of integrin alpha5beta1 and an integrin-mediated signal transduction molecule, focal adhesion kinase, was also increased in RMG-1-hFUT cells. Interestingly, anti-Le(Y) antibodies were revealed to immunoprecipitate integrin alpha5beta1, indicating that its oligosaccharides are composed of Le(Y), the amounts of which was substantially elevated in RMG-1-hFUT cells. The adhesion and spreading potentials on fibronectin-coated plates of RMG-1-hFUT cells were significantly enhanced in comparison to those of RMG-1 cells, and were greatly suppressed by anti-Le(Y) antibodies, indicating that Le(Y) is involved in the integrin-fibronectin interaction. These results suggested that transfection of the alpha1,2-fucosyltransferase gene into ovarian carcinoma-derived cells brought about elevated expression of integrin alpha5beta1 with Le(Y), resulting in enhancement of the adhesion and spreading potentials of cells through the integrin-fibronection interaction, which was inhibited by anti-Le(Y) antibodies. Thus, Le(Y) in integrin alpha5beta1 was thought to be involved in the enhanced cell adhesion properties of malignant ovarian carcinomas.

To improve light extraction efficiency and heat dissipation of sapphire-based light-emitting diodes (LEDs), we develop and optimize copper heat spreader which was electroformed in close contact with sapphire. On the basis of simulation results, an LED with copper lowers junction temperature when compared with the LED without copper. In addition, a copper-surrounded LED with protruded bottom surface exhibits almost the same thermal performance as that with flat bottom surface. In practical fabrication, all the LED samples with copper show significant reduction in junction temperature form 150.4°C for the original LED to less than 100°C at injection current of 1 A (∼ 3 W/mm2). The encapsulated LED at the same driven current yields an output power of ∼700 mW, which is 2.7 times higher than that of the original LED without copper.

To investigate the influence of Lewis y antigen on the gene expression of partial drug resistance associated proteins in human ovarian cancer cell line RMG-I-H.RT-PCR was used to determine the gene expressions of partial drug resistance associated proteins in RMG-I-H cell line transfected with alpha1, 2-fucosyltransferases gene and RMG-I cell line, as well as in RMG-I-H treated with or without anti-Lewis y monoclonal antibody at the concentration of 10 micro/g/ml. The immunocytochemical method was used to detect the expression of P-glycoprotein (P-gp) in RMG-I and RMG-I-H cell lines. RMG-I and RMG-I-H cells were transplanted into nude mice and the expression of P-gp in the tissues was measured by immunohistochemistry.The mRNA expressions of protein kinase C-alpha (PKC-alpha), topoismerase I ( Topo I ), multidrug resistance-associated protein-1 (MRP-1), and MRP-2 were significantly higher in RMG-I-H cells than those in RMG-I cells (0.46 +/- 0.02 vs. 0.27 +/- 0.05, 0.82 +/- 0.08 vs. 0.52 +/- 0.04, 0.66 +/- 0.07 vs. 0.34 +/- 0.12, and 0.44 +/- 0.08 vs. 0.23 +/- 0.05; all P0.05). However, the mRNA expression of multi-drug resistance 1 (MDR-1) was significantly lower in RMG-I-H cells than that in RMG-I cells (0.26 +/- 0.05 vs. 0.45 +/- 0.08, P0.05). The P-gp level increased in RMG-I-H cells compared with that in RMG-I cells both in vivo and in vitro (P0.05). Expressions of MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA decreased by the time in RMG-I-H cells treated with anti-Lewis y monoclonal antibody (all P0.05), while mRNA expressions of those genes in the control group did not statistically change (P0.05). In addition, MDR-1, MRP-1, MRP-2, PKC-alpha, and Topo I mRNA expressions were significantly lower in RMG-I-H cells treated with anti-Lewis y monoclonal antibody than those in the control group at 6 hours (all P0.05) and the inhibition ratios were 48.55%, 77.50%, 70.18%, 45.86%, and 46.13%, respectively.The Lewis y antigen of the human ovarian cancer cell surface is closely correlated with the regulation on the gene expression of partial drug resistance associated proteins.

For the maximize profits, the decision of how to obtain optimal quantity for the two kinds of perishable high-tech products is discussed, with two- direction substitutable demand and considering the cost of out-of-stock products. By establishing stochastic demand model, the optimal ordering quantity policy is derived, with two- direction substitutable demand. A numerical example is used to demonstrate that vendors would gain more profits due to taking into account the two- direction substitution between the perishable high-tech products.

For the maximize profits, the decision of how to obtain optimal quantity for the perishable high-tech products of two generations is discussed, with downwards substitutable demand and considering the cost of out-of-stock products. By establishing stochastic demand model, the optimal ordering quantity policy is derived, with downwards substitutable demand. A numerical example is used to demonstrate that vendors would gain more profits due to taking into account the downward substitution between the perishable high-tech products. In addition, when vendors carry out substitutable strategy, they should order more products of new generation and fewer products of old generation.

This paper indicates the implications and characteristics of supply chain, and the key evaluation index system in the course of selecting strategic supplier of supply chain is established and proposes an approach that Principal Component Analysis (PCA) can solve the problem of choosing the suppliers of supply chain. A numerical example is given to demonstrate the effectiveness of the proposed approach.

To evaluate single-dose and multiple-dose pharmacokinetics of cytotoxic T-lymphocyte-associated antigen 4 fusion protein (CTLA4Ig) in healthy volunteers and patients with rheumatoid arthritis (RA).The clinical trials included two phase I open studies: study 1 was an open-label dose-escalation study in 27 healthy volunteers and study 2 was a single-group, open-label study in patients with rheumatoid arthritis. In study 2, 9 patients were arranged to receive 10 mg/kg of CTLA4Ig at 0, 2, 4, 8, 12, and 16 weeks. The concentration-time data obtained by a validated ELISA method were subjected to non-compartmental pharmacokinetic analysis by DAS 2.1 software.In study 1, serum CTLA4Ig concentrations climbed rapidly to the peak and declined slowly with a t(1/2) of 15.1+/-2.6 d, 14.2+/-2.3 d, and 11.8+/-1.2 d after a single infusion of 1, 10, and 20 mg/kg, respectively. C(max) and AUC(0-infinity) increased proportionally with the dose. In study 2, the steady-state condition for CTLA4Ig following multiple doses of 10 mg/kg appeared to be attained at the fourth dose (d 56), with peak and trough concentrations of 239.8+/-45.3 mg/L and 20.5+/-7.9 mg/L, respectively. After multiple infusions, serum concentrations dropped slowly and the terminal half-life was 12.6+/-4.7 d.Intravenous infusion of CTLA4Ig was well tolerated in healthy volunteers and patients with rheumatoid arthritis. CTLA4Ig exhibited linear pharmacokinetics over the dose range of 1 to 20 mg/kg in healthy volunteers. The pharmacokinetics in RA patients appeared to be similar to that in healthy volunteers. No system accumulation appeared upon repeated infusions of 10 mg/kg every 4 weeks.

To explore the effect of alpha1,2-fucosyltransferase (alpha1,2-FT) gene on the biological behavior of ovarian carcinoma cells, the expression vector pcDNA3.1 -HFUT-H which containing human alpha1,2-FT gene coding region was constructed and transfected into ovarian carcinoma cell line RMG-I. alpha1,2-FT gene expression, Lewis y antigen expression, alpha1,2-FT activity, rates of cell growth and tumorogenesis in nude mice were compared before and after RMG-I being transfected. The transfection of alpha1,2-FT gene significantly increased the expression of alpha1,2-FT gene and Lewis y antigen in RMG-I cells. After the transfection, RMG-I cells showed remarkable improvement of alpha1,2-FT activity, cell proliferation, the ability of colony formation in soft agar and tumorogenesis in nude mice. The growth rates of alpha1,2-FT gene transfected RMG-I cells were obviously increased, presenting that the proportion of the cells in G2-M and S phases was obviously increased from 2.05% to 7.32% and from 23.95% to 33.27% respectively, and that of the cells in G1 phase was obviously decreased from 74.14% to 59.46%, as compared with the control group. These findings indicate that alpha1,2-FT and Lewis y antigen have the ability to enhance the proliferation and elevate the survival rates of RMG-I cells, which can promote the genesis and development of ovarian carcinoma.

This paper analyzes the problem of quantity decision and production planning in a supply chain, which is composed of one manufacturer and one retailer to meet the random demand of short-life-cycle products. To study the coordination of two ordering strategy, an optimization function aiming at maximizing total expected profits is established. Then the model is analyzed by the use of the numerical method, and the results of one ordering opportunity with those of two ordering opportunities under different parameters are compared. Then we show that two ordering opportunities strategy can not only improve the expected profits of the supply chain, but also effectively coordinate the supply chain system.

The malignant biological behaviors are enhanced in human ovarian cancer cell line RMG-1 after transfection of alpha1,2-fucosyl transferase (alpha1,2-FT) gene. This study was to investigate the influence of alpha1,2-FT gene transfection on cancer-related gene expression profile of RMG-1 cells.Gene expressing vector pcDNA3.1-HFT-H and empty vector pcDNA3.1 were transfected into RMG-1 cells to produce RMG-1-H and RMG-1-C cells separately. Gene expression profiles of these two cell lines were detected by gene chip assay. The acquired data were inquired on the GoMiner online database.After transfection, comparing with those in RMG-1-C cells, 88 differentially expressed genes were identified in RMG-1-H cells: 60 were up-regulated and 28 were down-regulated. These genes are involved in protein binding, nucleotide binding, cell proliferation, DNA-dependent regulation of transcription, signal transduction, protein amino acid phosphorylation, transcription, cell adhesion, and so on.The transfection of alpha1,2-FT gene causes the changes of gene expression profile in ovarian cancer RMG-1 cells.

To transfect human alpha1, 2-fucosyltransferase (alpha1, 2-FT) gene to ovarian cancer cell line RMG-I and investigate the antigenic expression change of Lewis y and the other related oligosaccharides.The expression vector pcDNA3.1(-)-HFUT-H was constructed by polymerase chain reaction (PCR) to clone human alpha1, 2-FT gene coding region. The alpha1, 2-FT gene stable high-expression cell line RMG-I-H was established by transfecting pcDNA3.1(-)-HFUT-H to ovarian cell line RMG-I. The change of alpha1, 2-FT activity in the cell line before and after the tranfection was confirmed by the determination of enzymatic activity. The changes of cell lipid and glucolipid, especially the change of type II oligosaccharide, in the cell line before and after the transfection was determined by Thin-Layer Chromatography (TLC) and TLC immunostaining method, respectively.The H-1 antigen and Lewis y antigen were obviously increased in the cell line RMG-1-H, especially the latter one, which was 20 times higher than before, and the type I saccharide chain Lewis b was decreased significantly. The main lipid components on the cell membrane, cholesterol and phosphatides, showed no change in the cell lines before and after the transfection, and the neutral glycolipid also showed no obvious change.The transfection of alpha1, 2-FT gene can increase the activity of alpha1, 2-FT in the cell line RMG-I and mainly increase the expression of Lewis y antigen simultaneously. The construction of RMG-I Lewis y high expression cell line provides a cell model for further study on the relationship between Lewis y antigen and biological behaviors in the ovarian cancer.

In this paper, we consider the problem of quantity decision in a supply chain, which is composed of one manufacture and one retailer to meet the random demand of a single product. We model the incentives of both parties and investigate the effect of flexibility eta, inventory cost and transit cost on the performance of two parties. Then we assume that the retail price is the reduction function of time, and a quantity flexibility contract model is established. An example is given to illustrate that the model not only improves the total profit of the supply chain but also coordinates the supply chain system.

To study the inhibitory effect of anti-Lewis y monoclonal antibody on proliferation, adhesion and invasion of alpha1, 2-fucosyltransferase gene transfected human ovarian cancer cell line RMG-I-H with over-expression of Lewis y antigen in vitro.The changes of proliferation, adhesion and invasion of RMG-I-H cells in vitro were detected by cell growth assay, cell adhesive assay and cell invasive assay, respectively, with goat anti-human IgG antibody treated group or non-antibody treated group as control.The proliferation and adhesion of RMG-I-H cells were remarkably inhibited by preincubation of the tumor cells with anti-Lewis y antibody in vitro (P0.05). The growth inhibitory rate from the second day to the seventh day was 5.62%, 19.75%, 34.96%, 46.51%, 49.78% and 33.33%, respectively. The adhesion inhibitory rate at different time points (15, 30, 60 min) was 47.59%, 58.64% and 13.85%, respectively. Invasive assay with a transwell cell culture chamber showed that there were no significant differences of invasion in vitro between each concentration of the Lewis y antibody treated group and non-antibody treated group (P0.05).Anti-Lewis y antibody significantly inhibits the proliferation and adhesion of RMG-I-H cells cultured in vitro, but it has no effect on invasion, which indicates that Lewis y is associated with some biological behaviors, such as proliferation and adhesion. The antibody against Lewis y may be an effective anti-metastasis agent for the treatment of patients with ovarian cancer.

The dorsal raphe nucleus (DRN)-serotonin (5-HT) system plays a key role in stress-related psychiatric disorders such as anxiety and depression. The habenular nucleus (Hb) is closely connected with the DRN both morphologically and functionally. Here, we used two types of depressive animal models by exposing rats to chronic mild stress (CMS) and by chronically administering the tricyclic antidepressant clomipramine (CLI) in the rat during the neonatal state of life to produce adult depressed rats. We investigated the effects of lateral habenular nucleus (LHb) lesions on the behavioral response and on the level of 5-HT in DRN in the depressed rats. Forced-swimming test (FST) showed that the immobility time decreased, and the climbing time increased after lesioning LHb of depressed rats. Microdialysis results indicated that the 5-HT level in DRN in depressed rats was lower than that of the control group. Lesion of the LHb was followed by an increased 5-HT turnover in the DRN. Our results suggested that the lesion of the LHb could improve the behavioral response of the depressed rats and the 5-HT level of the DRN increased by LHb lesions could be involved in the effects.

The purpose of this study is to examine satisfaction level and relevant factors of computerized nursing operation at one medical center in southern Taiwan. Structure and non-structure questionnaire survey is conducted on 96 nursing staffs through "Questionnaire of Satisfaction Level toward Computerized Nursing Operation." The results indicated that satisfaction level ranked between fair and satisfied, nursing record is the item with the highest score, and the question "Linking medical advice and instruction to nursing records to save typing time" scored the highest. In addition, basic properties of nursing staffs such as working years, current rank, and the years of using computerized nursing operation reached statistic significance. The results in this study are able to serve as the reference for nursing information designers.

To compare the substrate specificity of three murine GDP fucose: beta-galactoside alpha1,2-fucosyltransferases (alpha1,2-FT).Three members of MFUT- I, -II and -III, coding for a alpha1,2-FT, a GDP-fucose, were cloned from a cDNA of murine small intestine by reverse transcription-polymerase chain reaction. The coding regions were ligated into mammalian expression vector pcDNA 3.1 (pcDNA3.1-MFUT-I, pcDNA3.1-MFUT- II , and pcDNA3.1-MFUT- III) and were transiently transfected into COS-7 cells using a cellphect transfection kit. Then the cells were analyzed for expression and function of alpha1,2-FT and the substrate specificity of three alpha1,2-FT was compared.MFUT- I, -II, and -III exhibited sequence homology with human H (77%), Se (79%), and Sec1 (75%) genes, respectively. COS-7 cells transfected with pcDNA3.1-MFUT- I and pcDNA3.1-MFUT- II showed alpha1,2-FT activity, but no activity was detected in COS-7 cells transfected with pcDNA3.1- MFUT-III. MFUT- II showed alpha1,2-FT activity with both asialo-monosialoteterahexosyl ganglioside (GA1) and monosialoteterahexosyl ganglioside (GM1) as substrates to produce fucosyl GA1(FGA1) and fucosyl GM1(FGM1), respectively, but MFUT- I only showed alpha1,2-FT activity with GA1. The relative activity of MFUT- II with GA1 was 80-90-folds higher compared with MFUT- I, and the relative activity of MFUT- II with GA1 was 10-20-folds higher than that of GM1. The fucosyltransferase encoded by the MFUT- II gene showed the enzyme activity not only responsible for the synthesis of type 4-H antigens FGA1 and FGM1, but also responsible for the synthesis of type 1-H and 2-H antigens with lactotetraosylceramide and neolactotetraosylceramide as substrates.MFUT- II is the main alpha1,2-FT in mouse and MFUT- II can product type 4-H antigen FGA1 and FGM1, but MFUT- I only synthesizes FGA1. MFUT-III has no alpha1,2-FT activity.