Sample records for macc1 specific small

  1. Prognostic Value of MACC1 and c-met Expressions in Non-small Cell Lung Cancer

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    Xingsheng HU


    Full Text Available Background and objective It has been proven that metastasis-associated in colon cancer 1 (MACC1 is a new gene that is related to the invasion and metastasis of tumors. MACC1 also regulates c-met expression. The aim of this study is to explore the expressions of MACC1 and hepatocyte growth factor receptor (c-met, and its relationship with invasion, metastasis, and prognosis of non-small cell lung cancer (NSCLC. Methods MACC1 and c-met expressions were detected in 103 cases of NSCLC and 40 cases of neighboring normal lung cancer tissue using immunohistochemistry. Results MACC1 and c-met expressions were significantly higher in lung cancer tissues than that in neighboring normal tissue (P<0.001. MACC1 and c-met expressions were associated with poor differentiation, advanced T stages, lymph node metastasis, and advanced TNM stages (P<0.05 of NSCLC, but not with sex, age, smoking, and histological classification (P>0.05. In addition, a positive correlation between MACC1 and c-met expressions was observed (r=0.403, P<0.001. The result from the Kaplan-Meier survival analysis showed that the five-year survival rate in patients with positive MACC1 and c-met expressions was remarkanly lower than that in patients with negative expressions (P<0.05. The result from the Cox regression analysis showed that MACC1 expression was an independent prognostic factor for NSCLC (P=0.026. Conclusion MACC1 and c-met have an important function in the differentiation, invasion, and metastasis of NSCLC. MACC1 and c-met have poor prognosis in patients with NSCLC. Moreover, MACC1 expression is an independent prognostic factor for NSCLC.

  2. MACC1基因siRNA对肺癌SBC-5细胞增殖和迁移的影响%Influence of MACC1 Gene expression on the proliferation and migration of SBC-5 lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    杨淑慧; 龙敏; 王希; 林芳; 张惠中


    目的:探讨MACC1(metastasis-associated in colon cancer l)基因特异性siRNA(small interfering RNA)对肺癌细胞系SBC-5体外增殖和迁移的影响.方法:化学合成MACC1基因特异性siRNA,阳离子脂质体LipofectamineTM 2000转染肺癌细胞系SBC-5细胞,RT-PCR和Western blot方法检测转染后SBC-5细胞中MACC1基因和蛋白的表达情况;MTT法检测细胞的生长增殖状况;划痕试验观察细胞迁移能力的改变.结果:MACC1基因特异性siRNA转染细胞后,SBC-5细胞MACC1的mRNA和蛋白表达水平明显降低,MTT试验和划痕试验观察到转染MACC1-siRNA的SBC-5细胞增殖、迁移能力明显减弱.结论:MACC1基因特异性siRNA可以明显抑制肺癌SBC-5细胞增殖和迁移,MACC1可能成为肺癌治疗的新靶点.%Objective: To investigate the influence of siRNA targeting metastasis - associated in colon cancer Ⅰ ( MACC1 ) gene on proliferation and migration of human lung cancer cell line SBC - 5 in vitro. Methods : The siRNA targeting MACC1 gene and negative control siRNA were chemically synthesized, and were then transiently transfected into human lung cancer cell line SBC - 5 hy LipofectamineTM 2000. Expression of MACC1 mRNA and protein in siRNA transfected cells were examined by RT - PCR and Western blotting analysis. Proliferation and migration of siRNA transfected SBC - 5 cells were examined by MTT and Wound healing assay. Results : Transfection of specific siRNA targeting MACC1 into SBC - 5 cells inhihited MACC1 gene expression and both mRNA and protein expression levels declined markedly. siRNA transfected SBC - 5 cells showed decreased ability of proliferation and migration. Conclusion : The specific siRNA targeting MACC1 gene can significantly inhibit proliferation and migration of SBC - 5 cells, MACC1 may serve as a potential target for gene therapy of lung cancer.

  3. Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma

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    Lu Canliang


    Full Text Available Abstract Background Metastasis-associated in colon cancer-1 (MACC1 is a newly identified gene that plays a role in colon cancer metastasis through upregulation of c-MET proto-oncogene (c-MET. However, the value of MACC1 as a potential biomarker for hepatocellular carcinoma (HCC remains unknown. Methods MACC1 mRNA expression in 128 HCC tissues was examined by quantitative polymerase chain reaction. To show the potential correlation of MACC1 and c-MET, c-MET was also analysed. Results MACC1 was more highly expressed in HCC than in non-HCC tissues (P = 0.009. High MACC1 expression was significantly increased in cases with high alpha fetoprotein (AFP (P = 0.025. A positive correlation was found between MACC1 and c-MET mRNAs (r = 0.235, P = 0.009. Both univariate and multivariate analyses revealed that MACC1 expression was associated with overall survival (OS and disease-free survival (DFS. Moreover, stratified analysis showed that tumour-node-metastasis (TNM stage I patients with high MACC1 levels had shorter OS and DFS than those with low MACC1. Conclusions MACC1 may identify low- and high-risk individuals with HCC and be a valuable indicator for stratifying the prognosis of TNM stage I patients. MACC1 may serve as a novel biomarker for HCC.

  4. MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma.

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    Chan Xie

    Full Text Available BACKGROUND: The metastasis-associated in colon cancer 1 gene (MACC1 has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC. METHODS: mRNA and protein levels of MACC1 expression in one normal liver epithelial cells THLE3 and 15 HCC cell lines were examined using reverse transcription-PCR and Western blot. MACC1 expression was also comparatively studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Immunohistochemistry was employed to analyze MACC1 expression in 308 clinicopathologically characterized HCC cases. Statistical analyses were applied to derive association between MACC1 expression scores and clinical staging as well as patient survival. RESULTS: Levels of MACC1 mRNA and protein were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. Significant difference in MACC1 expression was found in patients of different TNM stages (P<0.001. Overall survival analysis showed that high MACC1 expression level correlated with lower survival rate (P = 0.001. Importantly, an inverse correlation between MACC1 level and patient survival remained significant in subjects with early-stage HCC or with normal serum AFP level. CONCLUSIONS: MACC1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.

  5. 肿瘤转移的一个靶向治疗位点MACC1%A target site for the treatment of tumor meatastasis: MACC1

    Institute of Scientific and Technical Information of China (English)

    贺志云; 白志刚; 张忠涛


    Metastasis-associated in colon cancer-1 (MACC1) is a recently discovered gene associated with colon cancer metastasis,there is significant relationship indicated from some studies between MACC1 and different malignant tumors.It may play an important role in the regulation of tumors metastasis.This article reviewed the expression and regulating function of MACC1 in different cancers including colorectal cancer,hepatic cancer,gastric cancer,lung cancer,ovarian cancer,breast cancer,and so on.It may offer clues to find a new target for target treatment of cancer metastasis.%结肠癌转移相关基因-1(MACC1)是新近发现的一个与结肠癌密切相关的基因,研究表明,MACC1与多种恶性肿瘤的转移和复发有密切的相关性,可能在肿瘤转移的共同通路中起着至关重要的调控作用.本研究就MACC1在结肠癌、肝癌、胃癌、肺癌、卵巢癌和乳腺癌等多种恶性肿瘤中的表达与功能调控等方面进行综述,以期为肿瘤转移调控的靶向治疗提供一个新的方向.

  6. Prognostic Value of MACC1 in Digestive System Neoplasms: A Systematic Review and Meta-Analysis. (United States)

    Wu, Zhenzhen; Zhou, Rui; Su, Yuqi; Sun, Li; Liao, Yulin; Liao, Wangjun


    Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the prognostic value of MACC1 in digestive system neoplasms needs systematic evidence to verify. Therefore, we aimed to provide further evidence on this topic by systematic review and meta-analysis. Literature search was conducted in multiple databases and eligible studies analyzing survival data and MACC1 expression were included for meta-analysis. Hazard ratio (HR) for clinical outcome was chosen as an effect measure of interest. According to our inclusion criteria, 18 studies with a total of 2,948 patients were identified. Pooled HRs indicated that high MACC1 expression significantly correlates with poorer OS in patients with digestive system neoplasms (HR = 1.94; 95% CI: 1.49-2.53) as well as poorer relapse-free survival (HR = 1.94, 95% CI: 1.33-2.82). The results of subgroup studies categorized by methodology, anatomic structure, and cancer subtype for pooled OS were all consistent with the overall pooled HR for OS as well. No publication bias was detected according to test of funnel plot asymmetry and Egger's test. In conclusion, high MACC1 expression may serve as a prognostic biomarker to guide individualized management in clinical practice for digestive system neoplasms.

  7. 下调肝星状细胞 MACC1对胃癌细胞迁移侵袭能力的影响%Effect of down -regulating MACC1 by shRNA on invasion and migration of gastric carci-noma cells

    Institute of Scientific and Technical Information of China (English)

    袁园; 朱正秋


    Objective:By in vitro experiment to explore the regulatory effect of MACC1 gene silencing in HSC expressα-SMA,MMP -2,MMP -9 and HGF,and its effects on ability of migration and invasion of co -cultured gastric carcinoma cells.Methods:To construct targeting MACC1 gene eukaryotic expression interference plasmid (MACC1 -shRNA)and non -specific irrelevant interference plasmid (shNC),transient transfect them into HSC with lipofectamine -2000,named low -expression group(shRNA)and negative control group (NC)accordingly,non-transfected HSC treated as a blank control group(Blank -Ctrl).The above three groups of cells were cultured in accordance with routinel,the expression levels of MACC1,α-SMA,HGF,MMP -2 and MMP -9 in human hepatic stellate cells were detected by Western blot and RT -PCR.Three groups of cells were co -cultured with MGC803 gastric carcinoma cells in vitro,the capabilities of migration and invasion were measured by transwell assay.Results:Western -Blot results showed that the expression of MACC1,α-SMA,HGF,MMP -2 and MMP -9 protein in HSC was significantly lower than that in the negative group and blank control group after transfection of MACC1 -shRNA (P 0.05).Conclusion:Silencing MACC1 in hepatic stellate cells, can inhibit the expression of MMP -2,MMP -9 and HGF,and decrease the migration and invasion of gastric cancer cells in co -culture.%目的:通过体外实验探讨肝星状细胞(hepatic stellate cell,HSC)MACC1基因沉默后调节肝星状细胞激活标志物α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、肝细胞生长因子(hepatocyte growth fac-tor,HGF)、基质金属蛋白酶2(matrix metalloproteinase -2,MMP -2)、基质金属蛋白酶9(matrix metalloprotein-ase -9,MMP -9)的表达,以及对共培养胃癌细胞迁移侵袭能力的影响。方法:利用 RNA 干扰技术,构建针对MACC1基因的真核表达干涉质粒(MACC1-shRNA)、非特异性无关

  8. Targeting MACC1 by RNA interference inhibits proliferation and invasion of bladder urothelial carcinoma in T24 cells. (United States)

    Xu, Song-Tao; Ding, Xiang; Ni, Qing-Feng; Jin, Shao-Ju


    The purpose of this article is to research on whether MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma (BUC). In this study, the expression of MACC1 gene was knocked down by RNA interference (RNAi) in the T24 cell (human BUC cell). The transcription level of MACC1 was detected by RT-PCR. Activities of MACC1, caspase-3, caspase-8, Bax and Met (mesenchymal-epithelial transition factor) protein were measured by Western blot. The cell proliferation and apoptosis were detected by MTT and flow cytometry. The cell's invasion ability was performed on Matrigel transwell assay. We also detect MMP2 (metalloproteinase-2) proteins by ELISA. The results showed that the level of MACC1 mRNA and protein was significantly reduced after RNAi. MTT assay showed that the proliferation of T24 cell was decreased due to RNA interference. Apoptosis studies also showed that MACC1 gene interference in T24 loses its anti-apoptotic effects. The expression of apoptosis proteins (Caspase-3, Caspase-8 and Bax) increased significantly due to the MACC1 RNAi. The level of Met protein was down-regulated obviously due to RNAi. Transwell assay showed that invasion abilities of T24 cells were reduced obviously due to MACC1 RNAi. Further studies showed that the secretion of MMP-2 was reduced by RNAi. It can conclude that the ability of proliferation and invasion in T24 cells can be inhibited by RNAi-targeting MACC1. As a result, MACC1 can serve as a potential target for gene therapy of human bladder urothelial carcinoma.

  9. Prognostic significance of metastasis associated in colon cancer 1 (MACC1 expression in patients with gallbladder cancer

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    Lijian Chen


    Full Text Available Background: The clinical significance of metastasis associated in colon cancer 1 (MACC1, in human gallbladder cancer, is not yet established. This study was performed to assess the expression of MACC1 in benign and malignant gallbladder lesions, and to assess its clinicopathological significance. Materials and Methods: Tissue samples from resected gallbladder cancer (n = 70 and cholelithiasis (n = 70 were evaluated for MACC1 expression by immunohistochemical staining. Their expression was correlated with different clinicopathological parameters. Results: Cytoplasmic MACC1 expression was significantly higher (58.6% in gallbladder cancer than in chronic cholecystitis (27.1%, P 0.05. The univariate Kaplan-Meier analysis showed that a positive MACC1 expression was associated with decreased overall survival (P < 0.001. The multivariate Cox regression analysis showed that MACC1 expression and the histopathological subtypes were independent risk factors for disease-free survival. Conclusion: The expression of MACC1 might be closely related to carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

  10. SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer

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    Schmid Felicitas


    Full Text Available Abstract Background Colorectal cancer is one of the main cancers in the Western world. About 90% of the deaths arise from formation of distant metastasis. The expression of the newly identified gene metastasis associated in colon cancer 1 (MACC1 is a prognostic indicator for colon cancer metastasis. Here, we analyzed for the first time the impact of single nucleotide polymorphisms (SNPs in the coding region of MACC1 for clinical outcome of colorectal cancer patients. Additionally, we screened met proto-oncogene (Met, the transcriptional target gene of MACC1, for mutations. Methods We sequenced the coding exons of MACC1 in 154 colorectal tumors (stages I, II and III and the crucial exons of Met in 60 colorectal tumors (stages I, II and III. We analyzed the association of MACC1 polymorphisms with clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients’ survival (n = 154, stages I, II and III. Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells. Results We genotyped three MACC1 SNPs in the coding region. Thirteen % of the tumors had the genotype cg (rs4721888, L31V, 48% a ct genotype (rs975263, S515L and 84% a gc or cc genotype (rs3735615, R804T. We found no association of these SNPs with clinicopathological parameters or with patients’ survival, when analyzing the entire patients’ cohort. An increased risk for a shorter metastasis-free survival of patients with a ct genotype (rs975263 was observed in younger colon cancer patients with stage I or II (P = 0.041, n = 18. In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation. Conclusion In summary, the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients’ survival compared to MACC1 expression analysis alone. The ct genotype (rs

  11. Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1)Associates with Better Prognosis of Gastric Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Shao-hua Ge; Jia-fu Ji; Xiao-jiang Wu; Xiao-hong Wang; Xiao-fang Xing; Lian-hai Zhang; Yu-bing Zhu; Hong Du; Bin Dong; Ying Hu


    Objective: The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods: The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results: The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage Ⅲ carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression. Conclusion: MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

  12. SPON2, a newly identified target gene of MACC1, drives colorectal cancer metastasis in mice and is prognostic for colorectal cancer patient survival. (United States)

    Schmid, F; Wang, Q; Huska, M R; Andrade-Navarro, M A; Lemm, M; Fichtner, I; Dahlmann, M; Kobelt, D; Walther, W; Smith, J; Schlag, P M; Stein, U


    MACC1 (metastasis associated in colon cancer 1) is a prognostic biomarker for tumor progression, metastasis and survival of a variety of solid cancers including colorectal cancer (CRC). Here we aimed to identify the MACC1-induced transcriptome and key players mediating the MACC1-induced effects in CRC. We performed microarray analyses using CRC cells ectopically overexpressing MACC1. We identified more than 1300 genes at least twofold differentially expressed, including the gene SPON2 (Spondin 2) as 90-fold upregulated transcriptional target of MACC1. MACC1-dependent SPON2 expression regulation was validated on mRNA and protein levels in MACC1 high (endogenously or ectopically) and low (endogenously or by knockdown) expressing cells. Chromatin immunoprecipitation analysis demonstrated the binding of MACC1 to the gene promoter of SPON2. In cell culture, ectopic SPON2 overexpression induced cell viability, migration, invasion and colony formation in endogenously MACC1 and SPON2 low expressing cells, whereas SPON2 knockdown reduced proliferative, migratory and invasive abilities in CRC cells with high endogenous MACC1 and SPON2 expression. In intrasplenically transplanted NOD/SCID mice, metastasis induction was analyzed with control or SPON2-overexpressing CRC cells. Tumors with SPON2 overexpression induced liver metastasis (vs control animals without any metastases, P=0.0036). In CRC patients, SPON2 expression was determined in primary tumors (stages I-III), and survival time was analyzed by Kaplan-Meier method. CRC patients with high SPON2 expressing primary tumors demonstrated 8 months shorter metastasis-free survival (MFS) compared with patients with low SPON2 levels (P=0.053). Combining high levels of SPON2 and MACC1 improved the identification of high-risk patients with a 20-month shorter MFS vs patients with low biomarker expression. In summary, SPON2 is a transcriptional target of the metastasis gene MACC1. SPON2 induces cell motility in vitro and CRC

  13. Relationship between pathological characteristics of prostate cancer and MACC1, c-Met, Apaf-1 as well as Caspase-9 expression in tumor tissue

    Institute of Scientific and Technical Information of China (English)

    Hang-Yu Ai; Xue-De Qiu


    Objective:To study the MACC1, c-Met, Apaf-1 and Caspase-9 expression in prostate cancer tissue and their relationship with the pathological characteristics of tumor.Methods:Prostate cancer and benign prostatic hyperplasia patients who received surgical treatment in our hospital from May 2015 to March 2016 were selected as the research subjects, prostate cancer tissue and benign prostatic hyperplasia tissue were collected during surgery to determine MACC1, c-Met, Apaf-1 and Caspase-9 expression, and serum specimens were collected to determine miR-let7i, -32, -128, -196a and -218 expression levels.Results: mRNA content of MACC1 and c-Met in prostate cancer tissue were significantly higher than those in benign prostatic hyperplasia tissue while mRNA content of Apaf-1 and Caspase-9 were significantly lower than those in benign prostatic hyperplasia tissue, and the higher the Gleason grading and the higher the Whitmore-Prout staging, the higher the mRNA content of MACC1 and c-Met in prostate cancer tissue and the lower the mRNA content of Apaf-1 and Caspase-9; serum miR-32, miR-128 and miR-196a expression levels in prostate cancer patients were significantly higher than those in patients with benign prostatic hyperplasia and negatively correlated with the mRNA content of Apaf-1 and Caspase-9, and the expression levels of miR-let7i and miR-218 were significantly lower than those in patients with benign prostatic hyperplasia and negatively correlated with MACC1 and c-Met.Conclusion: High MACC1 and c-Met expression and low Caspase-9 and Apaf-1 expression are related to the occurrence and progression of prostate cancer, and the MACC1, c-Met, Apaf-1 and Caspase-9 expression in prostate cancer tissue are regulated by miRNAs.

  14. Site-specificity in small architectural interventions

    DEFF Research Database (Denmark)

    Marie Bruun Jespersen, Line


    This paper is investigating the concepts of site-specificity, place and experience as they have been interpreted in a number of projects with at strong emphasis on the characteristics of the site, in the form of small architectural or artistic interventions. The idea of site-specificity is re......-emerging in contemporary architectural discourse in a series of projects, in e.g. the Norwegian project ”National Tourist Roads”. The small architectural interventions consequently work with enhancing or framing the qualities of site and aim at being a mediating element between man and nature. In this paper two main...... specificity in the small architectural interventions. The paper concludes that the small architectural interventions operate with a narrow concept of site, and that the large variety of artistic strategies and types of site-specificity found in contemporary art could serve as inspiration to open up...

  15. The radiographic appearances of non-specific small intestinal ulceration

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, Thomas H.; Jackson, James E


    AIM: To determine the imaging characteristics of non-specific ulceration of the small intestine. MATERIALS AND METHODS: The radiographic investigations undertaken in three patients originally referred for visceral angiography in whom a histological diagnosis of non-specific ulceration of the small bowel was subsequently made were retrospectively reviewed. Two men and one woman aged from 17 to 24 years all presented with anaemia requiring blood transfusion. Visceral angiography was available for review in all three patients, abdominal computed tomography in two, and a small bowel enema and white cell scintigraphy in one. RESULTS: In all three patients an angiographic abnormality was present within the ileum consisting of irregularity of the vasa recta, an area of subtle increased vascularity and early venous return. A long, non-branching vessel interpreted as a persistent vitello-intestinal artery was seen in two of these patients. A CT abnormality was present in two individuals consisting of a focal area of thickened small bowel. The single small bowel enema demonstrated a focal stricture and the white cell scan showed localized accumulation of radioactivity within the pelvis. CONCLUSION: Non-specific small intestinal ulceration may produce abnormalities that are discernible on barium studies, computed tomography, radiolabelled white cell scanning and visceral angiography. Recognition of these findings may allow a pre-operative diagnosis of this condition. Bryant, T.H. and Jackson, J.E. (2001)

  16. Small RNA expression and strain specificity in the rat

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    de Bruijn Ewart


    Full Text Available Abstract Background Digital gene expression (DGE profiling has become an established tool to study RNA expression. Here, we provide an in-depth analysis of small RNA DGE profiles from two different rat strains (BN-Lx and SHR from six different rat tissues (spleen, liver, brain, testis, heart, kidney. We describe the expression patterns of known and novel micro (miRNAs and piwi-interacting (piRNAs. Results We confirmed the expression of 588 known miRNAs (54 in antisense orientation and identified 56 miRNAs homologous to known human or mouse miRNAs, as well as 45 new rat miRNAs. Furthermore, we confirmed specific A to I editing in brain for mir-376a/b/c and identified mir-377 as a novel editing target. In accordance with earlier findings, we observed a highly tissue-specific expression pattern for all tissues analyzed. The brain was found to express the highest number of tissue-specific miRNAs, followed by testis. Notably, our experiments also revealed robust strain-specific differential miRNA expression in the liver that is caused by genetic variation between the strains. Finally, we identified two types of germline-specific piRNAs in testis, mapping either to transposons or in strand-specific clusters. Conclusions Taken together, the small RNA compendium described here advances the annotation of small RNAs in the rat genome. Strain and tissue-specific expression patterns furthermore provide a strong basis for studying the role of small RNAs in regulatory networks as well as biological process like physiology and neurobiology that are extensively studied in this model system.

  17. Embedded Volttron specification - benchmarking small footprint compute device for Volttron

    Energy Technology Data Exchange (ETDEWEB)

    Sanyal, Jibonananda [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Fugate, David L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Woodworth, Ken [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nutaro, James J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kuruganti, Teja [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)


    An embedded system is a small footprint computing unit that typically serves a specific purpose closely associated with measurements and control of hardware devices. These units are designed for reasonable durability and operations in a wide range of operating conditions. Some embedded systems support real-time operations and can demonstrate high levels of reliability. Many have failsafe mechanisms built to handle graceful shutdown of the device in exception conditions. The available memory, processing power, and network connectivity of these devices are limited due to the nature of their specific-purpose design and intended application. Industry practice is to carefully design the software for the available hardware capability to suit desired deployment needs. Volttron is an open source agent development and deployment platform designed to enable researchers to interact with devices and appliances without having to write drivers themselves. Hosting Volttron on small footprint embeddable devices enables its demonstration for embedded use. This report details the steps required and the experience in setting up and running Volttron applications on three small footprint devices: the Intel Next Unit of Computing (NUC), the Raspberry Pi 2, and the BeagleBone Black. In addition, the report also details preliminary investigation of the execution performance of Volttron on these devices.

  18. Combination of Endothelial-Monocyte-Activating Polypeptide-II with Temozolomide Suppress Malignant Biological Behaviors of Human Glioblastoma Stem Cells via miR-590-3p/MACC1 Inhibiting PI3K/AKT/mTOR Signal Pathway (United States)

    Zhou, Wei; Liu, Libo; Xue, Yixue; Zheng, Jian; Liu, Xiaobai; Ma, Jun; Li, Zhen; Liu, Yunhui


    This study aims to investigate the effect of Endothelial-Monocyte-Activating Polypeptide-II (EMAP-II) combined with temozolomide (TMZ) upon glioblastoma stem cells (GSCs) and its possible molecular mechanisms. In this study, combination of EMAP-II with TMZ inhibited cell viability, migration and invasion in GSCs, and autophagy inhibitor 3-methyl adenine (3-MA) and chloroquine (CQ) partly reverse the anti-proliferative effect of the combination treatment. Autophagic vacuoles were formed in GSCs after the combination therapy, accompanied with the up-regulation of LC3-II and Beclin-1 as well as the down-regulation of p62/SQSTM1. Further, miR-590-3p was up-regulated and Metastasis-associated in colon cancer 1 (MACC1) was down-regulated by the combination treatment in GSCs; MiR-590-3p overexpression and MACC1 knockdown up-regulated LC3-II and Beclin-1 as well as down-regulated p62/SQSTM1 in GSCs; MACC1 was identified as a direct target of miR-590-3p, mediating the effects of miR-590-3p in the combination treatment. Furthermore, the combination treatment and MACC1 knockdown decreased p-PI3K, p-Akt, p-mTOR, p-S6 and p-4EBP in GSCs; PI3K/Akt agonist insulin-like growth factor-1(IGF-1) partly blocked the effect of the combination treatment. Moreover, in vivo xenograft models, the mice given stable overexpressed miR-590-3p cells and treated with EMAP-II and TMZ had the smallest tumor sizes, besides, miR-590-3p + EMAP-II + TMZ up-regulated the expression level of miR-590-3p, LC3-II and Beclin-1 as well as down-regulated p62/SQSTM1. In conclusion, these results elucidated anovel molecular mechanism of EMAP-II in combination with TMZ suppressed malignant biological behaviors of GSCs via miR-590-3p/MACC1 inhibiting PI3K/AKT/mTOR signaling pathway, and might provide potential therapeutic approaches for human GSCs.

  19. Specifics of phytomass combustion in small experimental device

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    Lenhard Richard


    Full Text Available A wood pellet combustion carries out with high efficiency and comfort in modern pellet boilers. These facts help to increase the amount of installed pellet boilers in households. The combustion process quality depends besides the combustion conditions also on the fuel quality. The wood pellets, which don`t contain the bark and branches represent the highest quality. Because of growing pellet demand, an herbal biomass (phytomass, which is usually an agricultural by-product becomes economically attractive for pellet production. Although the phytomass has the net calorific value relatively slightly lower than the wood biomass, it is often significantly worse in view of the combustion process and an emission production. The combustion of phytomass pellets causes various difficulties in small heat sources, mainly due to a sintering of fuel residues. We want to avoid the ash sintering by a lowering of temperature in the combustion chamber below the ash sintering temperature of phytomass via the modification of a burner design. For research of the phytomass combustion process in the small boilers is constructed the experimental combustion device. There will investigate the impact of cooling intensity of the combustion chamber on the combustion process and emissions. Arising specific requirements from the measurement will be the basis for the design of the pellet burner and for the setting of operating parameters to the trouble-free phytomass combustion was guaranteed.

  20. Small supernumerary marker chromosomes and their correlation with specific syndromes (United States)

    Jafari-Ghahfarokhi, Hamideh; Moradi-Chaleshtori, Maryam; Liehr, Thomas; Hashemzadeh-Chaleshtori, Morteza; Teimori, Hossein; Ghasemi-Dehkordi, Payam


    A small supernumerary marker chromosome (sSMC) is a structurally abnormal chromosome. It is an additional chromosome smaller than one chromosome most often lacking a distinct banding pattern and is rarely identifiable by conventional banding cytogenetic analysis. The origin and composition of an sSMC is recognizable by molecular cytogenetic analysis. These sSMCs are seen in different shapes, including the ring, centric minute, and inverted duplication shapes. The effects of sSMCs on the phenotype depend on factors such as size, genetic content, and the level of the mosaicism. The presence of an sSMC causes partial tris- or tetrasomy, and 70% of the sSMC carriers are clinically normal, while 30% are abnormal in some way. In 70% of the cases the sSMC is de novo, in 20% it is inherited from the mother, and in 10% it is inherited from the father. An sSMC can be causative for specific syndromes such as Emanuel, Pallister-Killian, or cat eye syndromes. There may be more specific sSMC-related syndromes, which may be identified by further investigation. These 10 syndromes can be useful for genetic counseling after further study. PMID:26322288

  1. Specific small nucleolar RNA expression profiles in acute leukemia. (United States)

    Valleron, W; Laprevotte, E; Gautier, E-F; Quelen, C; Demur, C; Delabesse, E; Agirre, X; Prósper, F; Kiss, T; Brousset, P


    Apart from microRNAs, little is known about the regulation of expression of non-coding RNAs in cancer. We investigated whether small nucleolar RNAs (snoRNAs) accumulation displayed specific signatures in acute myeloblastic and acute lymphoblastic leukemias. Using microarrays and high-throughput quantitative PCR (qPCR), we demonstrate here that snoRNA expression patterns are negatively altered in leukemic cells compared with controls. Interestingly, a specific signature was found in acute promyelocytic leukemia (APL) with ectopic expression of SNORD112-114 snoRNAs located at the DLK1-DIO3 locus. In vitro experiments carried out on APL blasts demonstrate that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML-RARalpha fusion protein in negative leukemic cell lines. Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell cycle modulation; its expression was implicated in the G0/G1 to S phase transition mediated by the Rb/p16 pathways. This study thus reports three important observations: (1) snoRNA regulation is different in normal cells compared with cancer cells; (2) a relationship exists between a chromosomal translocation and expression of snoRNA loci; and (3) snoRNA expression can affect Rb/p16 cell cycle regulation. Taken together, these data strongly suggest that snoRNAs have a role in cancer development.

  2. A design guide and specification for small explosive containment structures

    Energy Technology Data Exchange (ETDEWEB)

    Marchand, K.A.; Cox, P.A.; Polcyn, M.A. [Southwest Research Institute, San Antonio, TX (United States)


    The design of structural containments for testing small explosive devices requires the designer to consider the various aspects of the explosive loading, i.e., shock and gas or quasistatic pressure. Additionally, if the explosive charge has the potential of producing damaging fragments, provisions must be made to arrest the fragments. This may require that the explosive be packed in a fragment attenuating material, which also will affect the loads predicted for containment response. Material also may be added just to attenuate shock, in the absence of fragments. Three charge weights are used in the design. The actual charge is used to determine a design fragment. Blast loads are determined for a {open_quotes}design charge{close_quotes}, defined as 125% of the operational charge in the explosive device. No yielding is permitted at the design charge weight. Blast loads are also determined for an over-charge, defined as 200% of the operational charge in the explosive device. Yielding, but no failure, is permitted at this over-charge. This guide emphasizes the calculation of loads and fragments for which the containment must be designed. The designer has the option of using simplified or complex design-analysis methods. Examples in the guide use readily available single degree-of-freedom (sdof) methods, plus static methods for equivalent dynamic loads. These are the common methods for blast resistant design. Some discussion of more complex methods is included. Generally, the designer who chooses more complex methods must be fully knowledgeable in their use and limitations. Finally, newly fabricated containments initially must be proof tested to 125% of the operational load and then inspected at regular intervals. This specification provides guidance for design, proof testing, and inspection of small explosive containment structures.

  3. Small RNA pyrosequencing in the protozoan parasite Entamoeba histolytica reveals strain-specific small RNAs that target virulence genes (United States)


    Background Small RNA mediated gene silencing is a well-conserved regulatory pathway. In the parasite Entamoeba histolytica an endogenous RNAi pathway exists, however, the depth and diversity of the small RNA population remains unknown. Results To characterize the small RNA population that associates with E. histolytica Argonaute-2 (EhAGO2-2), we immunoprecipitated small RNAs that associate with it and performed one full pyrosequencing run. Data analysis revealed new features of the 27nt small RNAs including the 5′-G predominance, distinct small RNA distribution patterns on protein coding genes, small RNAs mapping to both introns and exon-exon junctions, and small RNA targeted genes that are clustered particularly in sections of genome duplication. Characterization of genomic loci to which both sense and antisense small RNAs mapped showed that both sets of small RNAs have 5′-polyphosphate termini; strand-specific RT-PCR detected transcripts in both directions at these loci suggesting that both transcripts may serve as template for small RNA generation. In order to determine whether small RNA abundance patterns account for strain-specific gene expression profiles of E. histolytica virulent and non-virulent strains, we sequenced small RNAs from a non-virulent strain and found that small RNAs mapped to genes in a manner consistent with their regulation of strain-specific virulence genes. Conclusions We provided a full spectrum analysis for E. histolytica AGO2-2 associated 27nt small RNAs. Additionally, comparative analysis of small RNA populations from virulent and non-virulent amebic strains indicates that small RNA populations may regulate virulence genes. PMID:23347563

  4. Small RNA expression and strain specificity in the rat

    NARCIS (Netherlands)

    Linsen, S.E.V.; de Wit, E.; de Bruijn, E.; Cuppen, E.


    BACKGROUND: Digital gene expression (DGE) profiling has become an established tool to study RNA expression. Here, we provide an in-depth analysis of small RNA DGE profiles from two different rat strains (BN-Lx and SHR) from six different rat tissues (spleen, liver, brain, testis, heart, kidney). We

  5. Worldsid small female side impact dummy specifications and prototype evaluation

    NARCIS (Netherlands)

    Been, B.W.; Meijer, R.; Bermond, F.; Bortenschlager, K.; Hynd, D.; Martinez, L.; Ferichola, G.


    The WorldSID program was set up to develop a new, worldwide acceptable, advanced technology, side impact crash test dummy for improved assessment of injury risk to car occupants in lateral collisions. Following the release of the mid-sized male WorldSID, the development of the small female WorldSID

  6. Specific Emissions of Harmful Substances from Small Boilers

    Directory of Open Access Journals (Sweden)

    Horák Jiøí


    Full Text Available Coal is on of the most important energy source and its significance will increase in a future. In Czech republic coal is except else widely used as a fuel for combustion in a small boilers (up to 50 kW. Low efficiency of the small boilers which is often below 50% together with high emissions of the harmful substances into near surroundings cause in average 40 – 70% of total local air pollution. The research was performed in a scope of the Grant no. 101/98/0820 of Grant Agency of Czech Republic was focused on quality of combustion process related to combustion efficiency and creation of harmful substances at combustion of domestic fuels. Experiments were performed to compare combustion of brown coal, clack coal, coke and black coal slurry. Extremely high creation of harmful substances (CO, NOX, solid particles and organic substances was measured when the black coal slurry was used as a fuel, measured in kg of emissions per GJ of burned fuel. Combustion of brown coal produced significant emissions of solid particles which bond harmful substances as metals, polyaromatic hydrocarbons and others together with high emissions of SO2 . Strong dependence between emissions of CO and low quality of combustion given by low combustion temperature, shortage of combustion air, not suitable design of after-combustion chamber and short duration of fuel presence in a combustion area was found out. Emissions of wide range of metals were investigated. The results of the research grant project describe and explain the combustion process and creation of harmful substances in small boilers plus give suggestions and recommendations leading to rational operation of the small boilers and lowering their negative impact to environment.

  7. Motivation of workers of specific production in a small firm


    Navrátilová, Hana


    The thesis is dealing with the motivation of human resources in a small firm producing the specialized medical equipment. The aim is to analyse the actual situation of a motivation stucture and work satisfaction through the use of an empirical research and to suggest recommendations for the improvement of this area of the company's human resource management. The theoretical part characterizes a question of work motivation, system of assessment and remuneration of workers including employee be...

  8. Specifically targeted gene therapy for small-cell lung cancer

    DEFF Research Database (Denmark)

    Christensen, C.L.; Zandi, R.; Gjetting, T.


    Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous....... This review describes and discusses the current status of the application of gene therapy in relation to SCLC Udgivelsesdato: 2009/4...... DNA into malignant cells causing them to die. Since SCLC is a highly disseminated malignancy, the gene therapeutic agent must be administered systemically, obligating a high level of targeting of tumor tissue and the use of delivery vehicles designed for systemic circulation of the therapeutic DNA...

  9. Proteoform-specific protein binding of small molecules in complex matrices (United States)

    Characterizing the specific binding between protein targets and small molecules is critically important for drug discovery. Conventional assays require isolation and purification of small molecules from complex matrices through multistep chromatographic fractionation, which may alter their original ...

  10. Radiolabeled prostate-specific membrane antigen small-molecule inhibitors. (United States)

    Will, Leon; Sonni, Ida; Kopka, Klaus; Kratochwil, Clemens; Giesel, Frederik L; Haberkorn, Uwe


    Prostate cancer (PC) is one of the most common malignancies worldwide. Prostate-specific membrane antigen (PSMA) has been found to be expressed in most PCs and represents an ideal target for diagnostic and therapeutic purposes. Numerous PSMA tracers have been recently developed. This review aims to provide an overview on the clinical influence of PSMA tracers in primary staging, biochemical recurrence (BCR) of PC and advanced, metastatic PC. Additionally, the use of PSMA tracers in systemic radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC), as well as non-prostatic specific uptake of PSMA tracers and the use of PSMA imaging to manage therapy have been described. A computerized search of the literature (PubMed) was conducted in order to find evidence on the role of PSMA tracers in the diagnosis and therapy of PC. PSMA positron-emission tomography/computed tomography (PET/CT) outperforms conventional imaging in the settings of primary PC, BCR and advanced PC. Especially in BCR of PC, PSMA PET/CT shows clinical value with significantly higher detection rates than standard modalities. The use of PSMA PET/CT resulted in a change of the therapeutic management in up to half of the cases. Regarding RLT, smaller studies were able to show positive clinical effects of 177Lu-labeled PSMA tracers without the occurrence of severe side effects. The currently available data clearly shows that PSMA targeting has a clinical impact on the diagnosis of PC, and that RLT using radiolabeled PSMA tracers has high potentiality in the settings of resistance to conventional therapeutic approaches.

  11. Intestinal perforation caused by non specific idiopathic ulcer of the small intestine. A case report. (United States)

    Cavallaro, V; Racalbuto, A; Russello, D; Succi, L; Fragati, G; Catania, V


    A case of non specific idiopathic ulcer of the small intestine in a 79-year-old patient is reported. On admission he presented with acute abdomen and was submitted to wide intestinal resection. The features of this rare disease (only 370 cases described until 1987), which has an undefined etiopathogenesis, severe symptoms, and poses diagnostic problems, are discussed.

  12. Multiple chronic non-specific ulcer of small intestine characterized by anemia and hypoalbuminemia

    Institute of Scientific and Technical Information of China (English)


    A female patient with anemia and hypoalbuminemia was admitted to our hospital due to an over 20-year history of recurrent dizziness,fatigue and ankle edema.She was diagnosed as multiple chronic nonspecific ulcer of the small intestine characterized by non-specific histology and persistent gastrointestinal bleeding.

  13. Small ubiquitin-like modifier protein-specific protease 1 and prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Yong Zuo; Jin-Ke Cheng


    Small ubiquitin-like modifier protein (SUMO) modification is a highly dynamic process,catalyzed by SUMO-specific activating (E1),conjugating (E2) and ligating (E3) enzymes,and reversed by a family of SUMO-specific proteases (SENPs).There are six members of the human SENP family,and each SENP has different cellular locations and substrate specificities.However,the precise roles of SENPs in cellular processes have not been elucidated to date.This brief review will focus on recent advances pertaining to the identified targets of SENP 1 and its potential role in prostate cancer.

  14. Small organic probes as amyloid specific ligands--past and recent molecular scaffolds. (United States)

    Nilsson, K Peter R


    Molecular probes for selective staining and imaging of protein aggregates, such as amyloid, are important to advance our understanding of the molecular mechanisms underlying protein misfolding diseases and also for obtaining an early and accurate clinical diagnosis of these disorders. Since normal immunohistochemical reagents, such as antibodies have shown limitation for identifying protein aggregates both in vitro and in vivo, small organic probes have been utilized as amyloid specific markers. In this review, past and recent molecular scaffolds that have been utilized for the development of small organic amyloid imaging agents are discussed.

  15. Study of Small Ligands Which Bind Specifically to Breast Cancer Cells (United States)


    to a target may yield useful specific small peptide binders. Library screening with streptavidin The quality of the RPL was confirmed by screening...high and low pH buffers. A total of four pans were performed. Library screening with live cells overexpressing ErbB2 Our first screening attempt was...consensus which was related to sequences which were identified using purified protein screenings (see alignment). Library screening with purified

  16. Selection of RNAs for constructing "Lighting-UP" biomolecular switches in response to specific small molecules.

    Directory of Open Access Journals (Sweden)

    Tamaki Endoh

    Full Text Available RNA and protein are potential molecules that can be used to construct functional nanobiomaterials. Recent findings on riboswitches emphasize on the dominative function of RNAs in regulating protein functions through allosteric interactions between RNA and protein. In this study, we demonstrate a simple strategy to obtain RNAs that have a switching ability with respect to protein function in response to specific target molecules. RNA aptamers specific for small ligands and a trans-activation-responsive (TAR-RNA were connected by random RNA sequences. RNAs that were allosterically bound to a trans-activator of transcription (Tat-peptide in response to ligands were selected by repeated negative and positive selection in the absence and presence of the ligands, respectively. The selected RNAs interacted with artificially engineered Renilla Luciferase, in which the Tat-peptide was inserted within the Luciferase, in the presence of the specific ligand and triggered the "Lighting-UP" switch of the engineered Luciferase.

  17. Substrate specificity determinants of the methanogen homoaconitase enzyme: structure and function of small subunit residues

    Energy Technology Data Exchange (ETDEWEB)

    Jeyakanthan, Jeyaraman [National Synchrotron Radiation Research Center; Drevland, Randy [University of Texas, Austin; Gayathri, Dasara [University of Madras; Velmurugan, Devadasan [University of Madras; Shinkai, Akeo [SPring8/JASRI, Mikazuki, Hyogo and RIKEN, Japan; Kuramitsu, Seiki [SPring8/JASRI, Mikazuki, Hyogo and RIKEN, Japan; Yokoyama, Shigeyuki [University of Tokyo, Tokyo, Japan; Graham, David E [ORNL


    The aconitase family of hydro-lyase enzymes includes three classes of proteins that catalyze the isomerization of -hydroxyacids to -hydroxyacids. Besides aconitase, isopropylmalate isomerase (IPMI) proteins specifically catalyze the isomerization of , -dicarboxylates with hydrophobic -chain groups, and homoaconitase (HACN) proteins catalyze the isomerization of tricarboxylates with variable chain length -carboxylate groups. These enzymes stereospecific hydro-lyase activities make them attractive catalysts to produce diastereomers from unsaturated precursors. However, sequence similarity and convergent evolution among these proteins leads to widespread misannotation and uncertainty about gene function. To find the substrate specificity determinants of homologous IPMI and HACN proteins from Methanocaldococcus jannaschii, the small-subunit HACN protein (MJ1271) was crystallized for X-ray diffraction. The structural model showed characteristic residues in a flexible loop region between 2 and 3 that distinguish HACN from IPMI and aconitase proteins. Site-directed mutagenesis of MJ1271 produced loop-region variant proteins that were reconstituted with wild-type MJ1003 large-subunit protein. The heteromers formed promiscuous hydro-lyases with reduced activity but broader substrate specificity. Both R26K and R26V variants formed relatively efficient IPMI enzymes, while the T27A variant had uniformly lower specificity constants for both IPMI and HACN substrates. The R26V T27Y variant resembles the MJ1277 IPMI small subunit in its flexible loop sequence, but demonstrated the broad substrate specificity of the R26V variant. These mutations may reverse the evolution of HACN activity from an ancestral IPMI gene, demonstrating the evolutionary potential for promiscuity in hydro-lyase enzymes. Understanding these specificity determinants enables the functional reannotation of paralogous HACN and IPMI genes in numerous genome sequences. These structural and kinetic results will

  18. Evolution of Specific Antibodies and Proviral DNA in Milk of Small Ruminants Infected by Small Ruminant Lentivirus

    Directory of Open Access Journals (Sweden)

    Ana Domenech


    Full Text Available The diagnosis of Small Ruminant Lentivirus (SRLV is based on clinical signs, pathological lesions and laboratory testing. No standard reference test for the diagnosis of maedi visna has been validated up to the present, and it is puzzling that tests which detect antibodies against the virus and tests which detect the proviral genome may render opposite results. The aim of this study was to evaluate the presence in milk throughout a lactation period of specific antibodies by ELISA and of SRLV proviral DNA by a PCR of the highly conserved pol region. A six-month study was conducted with the milk of 28 ewes and 31 goats intensively reared. The percentage of animals with antibodies against SRLV increased throughout the study period. Seroprevalence in sheep was 28% at the beginning of the study and by the end it had increased up to 52.4%. In goats, initial seroprevalence of 5.6% increased to 16%. The percentage of PCR positive ewes was stable throughout the study period. Of the positive sheep, 21.4% were PCR-positive before antibodies could be detected and most of them became PCR-negative shortly after the first detection of antibodies. This might suggest that antibodies have a neutralizing effect. In addition, an equal percentage of sheep were always PCR-negative but either became ELISA-positive or was always ELISA-positive, which might support this hypothesis. On the other hand, the PCR results in goats did not follow any pattern and oscillated between 35.3% and 55.6% depending on the month. Most goats positive by PCR failed to develop antibodies in the 6 months tested. We may conclude that the infection and the antibody response to it follow a different trend in sheep and goats.

  19. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. (United States)

    Gao, Yuan; Dickerson, J Bradley; Guo, Fukun; Zheng, Jie; Zheng, Yi


    The signaling pathways mediated by Rho family GTPases have been implicated in many aspects of cell biology. The specificity of the pathways is achieved in part by the selective interaction between Dbl family guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. Here, we report a first-generation small-molecule inhibitor of Rac GTPase targeting Rac activation by GEF. The chemical compound NSC23766 was identified by a structure-based virtual screening of compounds that fit into a surface groove of Rac1 known to be critical for GEF specification. In vitro it could effectively inhibit Rac1 binding and activation by the Rac-specific GEF Trio or Tiam1 in a dose-dependent manner without interfering with the closely related Cdc42 or RhoA binding or activation by their respective GEFs or with Rac1 interaction with BcrGAP or effector PAK1. In cells, it potently blocked serum or platelet-derived growth factor-induced Rac1 activation and lamellipodia formation without affecting the activity of endogenous Cdc42 or RhoA. Moreover, this compound reduced Trio or Tiam1 but not Vav, Lbc, Intersectin, or a constitutively active Rac1 mutant-stimulated cell growth and suppressed Trio, Tiam1, or Ras-induced cell transformation. When applied to human prostate cancer PC-3 cells, it was able to inhibit the proliferation, anchorage-independent growth and invasion phenotypes that require the endogenous Rac1 activity. Thus, NSC23766 constitutes a Rac-specific small-molecule inhibitor that could be useful to study the role of Rac in various cellular functions and to reverse tumor cell phenotypes associated with Rac deregulation.

  20. Sequence-Specific Biosensing of DNA Target through Relay PCR with Small-Molecule Fluorophore. (United States)

    Yasmeen, Afshan; Du, Feng; Zhao, Yongyun; Dong, Juan; Chen, Haodong; Huang, Xin; Cui, Xin; Tang, Zhuo


    Polymerase chain reaction coupled with signal generation offers sensitive recognition of target DNA sequence; however, these procedures require fluorophore-labeled oligonucleotide probes and high-tech equipment to achieve high specificity. Therefore, intensive research has been conducted to develop reliable, convenient, and economical DNA detection methods. The relay PCR described here is the first sequence-specific detection method using a small-molecule fluorophore as a sensor and combines the classic 5'-3' exonuclease activity of Taq polymerase with an RNA mimic of GFP to build a label-free DNA detection platform. Primarily, Taq polymerase cleaves the 5' noncomplementary overhang of the target specific probe during extension of the leading primer to release a relay oligo to initiate tandem PCR of the reporting template, which encodes the sequence of RNA aptamer. Afterward, the PCR product is transcribed to mRNA, which could generate a fluorescent signal in the presence of corresponding fluorophore. In addition to high sensitivity and specificity, the flexibility of choosing different fluorescent reporting signals makes this method versatile in either single or multiple target detection.

  1. Molecular investigation of Cryptosporidium in small caged pets in northeast China: host specificity and zoonotic implications. (United States)

    Li, Qiao; Li, Lu; Tao, Wei; Jiang, Yanxue; Wan, Qiang; Lin, Yongchao; Li, Wei


    This study screened 151 pet-derived fecal specimens randomly collected from four commercial markets in northeast China for the presence of Cryptosporidium by genus-specific nested PCRs of the small subunit rRNA gene. Of these, 14 specimens (9.3 %) from nine species of birds, two types of rodents, and a hedgehog were positive for Cryptosporidium. Sequence analysis on the PCR-positive isolates facilitated identification of three Cryptosporidium species (C. baileyi, C. galli, and C. ubiquitum) and two Cryptosporidium genotypes (ferret genotype and avian genotype V). The study birds were affected predominantly with bird-specific C. baileyi (Atlantic canary, budgerigar, crested myna, rock dove, and silky fowl), C. galli (Chinese hwamei), and Cryptosporidium avian genotype V (Fischer's lovebird and rosy-faced lovebird). Cryptosporidium ferret genotype previously considered rodent-adapted was identified in three specimens from budgerigar, chipmunk, and red squirrel. Two specimens collected from common hill myna and hedgehog were positive for C. ubiquitum. The species of birds that can be colonized by Cryptosporidium were extended. Moreover, the data expanded the host range of Cryptosporidium ferret genotype and C. ubiquitum, especially the birds. The carriage of zoonotic C. ubiquitum in small caged pets is of public health importance.

  2. Tidal reversal and flow velocities using temperature and specific conductance in a small wetland creek (United States)

    Eaton, Timothy T.


    Characterizing flow dynamics in very small tidal creeks is complicated and not well suited to methods developed for upland streams or coastal estuaries, due to low flows, bidirectionality and shallow waters. Simple instrumentation enables thermal and salinity signals to be used to observe flow directions and estimate velocities in these settings. Using multiple inexpensive sensors over 500 m along a tidally influenced wetland creek, I demonstrate how advection of temperature and specific conductance pulses reveal flood and ebb tides and the temporary reversal of flow by warmer, estuarine water from the receiving embayment. The sequential rise of temperature upstream was most evident under hot and dry conditions, after daily peak air temperatures of 25 °C or above, and was subdued or disrupted under cooler or rainy conditions in summertime. Changes in specific conductance at successive sites upstream were less susceptible to environmental influences and confirm tidal flood velocity of between 0.07 and 0.37 m/s. The tidally-induced flow reversal suggests that periodic high tide conditions can interfere with rapid dispersal of pollution discharges, such as from the combined sewer overflow (CSO) located upstream of the studied creek reach. This low-cost approach of temperature and specific conductance sensing in vegetated coastal wetlands where access, precise elevation control and creek discharge measurements are difficult, provides a simple way of tracking water masses when sufficient contrast exists between water sources.

  3. Small-Chamber Measurements of Chemical-Specific Emission Factors for Drywall

    Energy Technology Data Exchange (ETDEWEB)

    Maddalena, Randy; Russell, Marion; Apte, Michael G.


    Imported drywall installed in U.S. homes is suspected of being a source of odorous and potentially corrosive indoor pollutants. To support an investigation of those building materials by the Consumer Products Safety Commission (CPSC), Lawrence Berkeley National Laboratory (LBNL) measured chemical-specific emission factors for 30 samples of drywall materials. Emission factors are reported for 75 chemicals and 30 different drywall samples encompassing both domestic and imported stock and incorporating natural, synthetic, or mixed gypsum core material. CPSC supplied all drywall materials. First the drywall samples were isolated and conditioned in dedicated chambers, then they were transferred to small chambers where emission testing was performed. Four sampling and analysis methods were utilized to assess (1) volatile organic compounds, (2) low molecular weight carbonyls, (3) volatile sulfur compounds, and (4) reactive sulfur gases. LBNL developed a new method that combines the use of solid phase microextraction (SPME) with small emission chambers to measure the reactive sulfur gases, then extended that technique to measure the full suite of volatile sulfur compounds. The testing procedure and analysis methods are described in detail herein. Emission factors were measured under a single set of controlled environmental conditions. The results are compared graphically for each method and in detailed tables for use in estimating indoor exposure concentrations.

  4. Small Cajal body-specific RNAs of Drosophila function in the absence of Cajal bodies. (United States)

    Deryusheva, Svetlana; Gall, Joseph G


    During their biogenesis small nuclear RNAs (snRNAs) undergo multiple covalent modifications that require guide RNAs to direct methylase and pseudouridylase enzymes to the appropriate nucleotides. Because of their localization in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific RNAs (scaRNAs). Using a fluorescent primer extension technique, we mapped the modified nucleotides in Drosophila U1, U2, U4, and U5 snRNAs. By fluorescent in situ hybridization (FISH) we showed that seven Drosophila scaRNAs are concentrated in easily detectable CBs. We used two assays based on Xenopus oocyte nuclei to demonstrate that three of these Drosophila scaRNAs do, in fact, function as guide RNAs. In flies null for the CB marker protein coilin, CBs are absent and there are no localized FISH signals for the scaRNAs. Nevertheless, biochemical experiments show that scaRNAs are present at normal levels and snRNAs are properly modified. Our experiments demonstrate that several scaRNAs are concentrated as expected in the CBs of wild-type Drosophila, but they function equally well in the nucleoplasm of mutant flies that lack CBs. We propose that the snRNA modification machinery is not limited to CBs, but is dispersed throughout the nucleoplasm of cells in general.

  5. Biomarkers for Tuberculosis Based on Secreted, Species-Specific, Bacterial Small Molecules. (United States)

    Pan, Shih-Jung; Tapley, Asa; Adamson, John; Little, Tessa; Urbanowski, Michael; Cohen, Keira; Pym, Alexander; Almeida, Deepak; Dorasamy, Afton; Layre, Emilie; Young, David C; Singh, Ravesh; Patel, Vinod B; Wallengren, Kristina; Ndung'u, Thumbi; Wilson, Douglas; Moody, D Branch; Bishai, William


    Improved biomarkers are needed for tuberculosis. To develop tests based on products secreted by tubercle bacilli that are strictly associated with viability, we evaluated 3 bacterial-derived, species-specific, small molecules as biomarkers: 2 mycobactin siderophores and tuberculosinyladenosine. Using liquid chromatography-tandem mass spectrometry, we demonstrated the presence of 1 or both mycobactins and/or tuberculosinyladenosine in serum and whole lung tissues from infected mice and sputum, cerebrospinal fluid (CSF), or lymph nodes from infected patients but not uninfected controls. Detection of the target molecules distinguished host infection status in 100% of mice with both serum and lung as the target sample. In human subjects, we evaluated detection of the bacterial small molecules (BSMs) in multiple body compartments in 3 patient cohorts corresponding to different forms of tuberculosis. We detected at least 1 of the 3 molecules in 90%, 71%, and 40% of tuberculosis patients' sputum, CSF, and lymph node samples, respectively. In paucibacillary forms of human tuberculosis, which are difficult to diagnose even with culture, detection of 1 or more BSM was rapid and compared favorably to polymerase chain reaction-based detection. Secreted BSMs, detectable in serum, warrant further investigation as a means for diagnosis and therapeutic monitoring in patients with tuberculosis.

  6. Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.

    Directory of Open Access Journals (Sweden)

    Takahiro Nagatake

    Full Text Available Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4, and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119, and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1. A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip, thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg, pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy, cholecystokinin (Cck, secretin (Sct, and tryptophan hydroxylase 1 (Tph1. In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells.

  7. Control of a specific motor program by a small brain area in zebrafish

    Directory of Open Access Journals (Sweden)

    Otto eFajardo


    Full Text Available Complex motor behaviors are thought to be coordinated by networks of brain nuclei that may control different elementary motor programs. Transparent zebrafish larvae offer the opportunity to analyze the functional organization of motor control networks by optical manipulations of neuronal activity during behavior. We examined motor behavior in transgenic larvae expressing channelrhodopsin-2 throughout many neurons in the brain. Wide-field optical stimulation triggered backward and rotating movements caused by the repeated execution of J-turns, a specific motor program that normally occurs during prey capture. Although optically evoked activity was widespread, behavioral responses were highly coordinated and lateralized. 3-D mapping of behavioral responses to local optical stimuli revealed that J-turns can be triggered specifically in the anterior-ventral optic tectum and/or the adjacent pretectum. These results suggest that the execution of J-turns is controlled by a small group of neurons in the midbrain that may act as a command center. The identification of a brain area controlling a defined motor program involved in prey capture is a step towards a comprehensive analysis of neuronal circuits mediating sensorimotor behaviors of zebrafish.

  8. High specificity but low sensitivity of mutation-specific antibodies against EGFR mutations in non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Bondgaard, Anna-Louise; Høgdall, Estrid; Mellemgaard, Anders;


    Determination of epidermal growth factor receptor (EGFR) mutations has a pivotal impact on treatment of non-small-cell lung cancer (NSCLC). A standardized test has not yet been approved. So far, Sanger DNA sequencing has been widely used. Its rather low sensitivity has led to the development...

  9. Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid

    Directory of Open Access Journals (Sweden)

    Christopher J. Petzold


    Full Text Available Cell density is the critical parameter controlling tendon morphogenesis. Knowing its neighbors allows a cell to regulate correctly its proliferation and collagen production. A missing link to understanding this process is a molecular description of the sensing mechanism. Previously, this mechanism was shown in cell culture to rely on a diffusible factor (SNZR [sensor] with an affinity for the cell layer. This led to purifying conditioned medium over 4 columns and analyzing the final column fractions for band intensity on SDS gels versus biological activity – a 16 kD band strongly correlated between assays. N-terminal sequencing – EPLAVVDL – identified a large gene (424 AA, extremely conserved between chicken and human. In this paper we probe whether this is the correct gene. Can the predicted large protein be cleaved to a smaller protein? EPLAVVDL occurs towards the C-terminus and cleavage would create a small 94 AA protein. This protein would run at ∼10 kD, so what modifications or cofactor binding accounts for its running at 16 kD on SDS gels? This protein has no prominent hydrophobic regions, so can it be secreted? To validate its role, the chicken cDNA for this gene was tagged with myc and his and transfected into a human osteosarcoma cell line (U2OS. U2OS cells expressed the gene but not passively: differentiating into structures resembling spongy bone and expressing alkaline phosphatase, an early bone marker. Intracellularly, two bands were observed by Western blotting: the full length protein and a smaller form (26 kD. Outside the cell, a small band (28 kD was detected, although it was 40% larger than expected, as well as multiple larger bands. These larger forms could be converted to the predicted smaller protein (94 AA + tags by changing salt concentrations and ultrafiltering – releasing a cofactor to the filtrate while leaving a protein factor in the retentate. Using specific degradative enzymes and mass spectrometry, the

  10. The role of the small GTPase Rap in Drosophila R7 photoreceptor specification (United States)

    Mavromatakis, Yannis Emmanuel; Tomlinson, Andrew


    The Drosophila R7 photoreceptor provides an excellent model system with which to study how cells receive and “decode” signals that specify cell fate. R7 is specified by the combined actions of the receptor tyrosine kinase (RTK) and Notch (N) signaling pathways. These pathways interact in a complex manner that includes antagonistic effects on photoreceptor specification: RTK promotes the photoreceptor fate, whereas N inhibits. Although other photoreceptors are subject to only mild N activation, R7 experiences a high-level N signal. To counter this effect and to ensure that the cell is specified as a photoreceptor, a high RTK signal is transduced in the cell. Thus, there are two levels of RTK transduction in the photoreceptors: in R7 it is high, whereas in others it is low. Here, we address how this high-level RTK signal is transduced in R7 and find that, in addition to Ras, another small GTPase, Rap, is also engaged. Thus, when N activity is high, a robust RTK signal operates that uses both Ras and Rap, but when N activity is low, only a mild RTK signal is transduced and Ras alone suffices for the purpose. PMID:22355117

  11. Organ-specific transcriptome response of the small brown planthopper toward rice stripe virus. (United States)

    Zhao, Wan; Lu, Lixia; Yang, Pengcheng; Cui, Na; Kang, Le; Cui, Feng


    Rice stripe virus (RSV) causes rice stripe disease and is transmitted by the small brown planthopper (Laodelphax striatellus, SBPH) in a persistent, circulative, and propagative manner. The alimentary canal and salivary gland of SBPH play important roles in viral replication and transmission. However, little is known about the underlying molecular functions of these two organs in the interaction between RSV and SBPH. In this study, organ-specific transcriptomes of the alimentary canal and salivary gland were analyzed in viruliferous and naïve SBPH. The number of differentially expressed unigenes in the alimentary canal was considerably greater than that in the salivary gland after RSV infection, and only 23 unigenes were co-regulated in the two organs. In the alimentary canal, genes involved in lysosome, digestion and detoxification were activated upon RSV infection, whereas the genes related to DNA replication and repair were suppressed. RSV activated RNA transport and repressed the MAPK, mTOR, Wnt, and TGF-beta signaling pathways in the salivary gland. The overall immune reaction toward RSV was much stronger in the salivary gland than in the alimentary canal. RSV activated the pattern recognition molecules and Toll pathway in the salivary gland but inhibited these two reactions in the alimentary canal. The responses from reactive oxygen and the immune-responsive effectors were stronger in the salivary gland than in the alimentary canal after RSV infection. These findings provide clues on the roles of the two organs in confronting RSV infection and aid in the understanding of the interaction between RSV and SBPHs.

  12. Group specific internal standard technology (GSIST) for simultaneous identification and quantification of small molecules (United States)

    Adamec, Jiri; Yang, Wen-Chu; Regnier, Fred E


    Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distince forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

  13. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer’s disease (United States)

    Habchi, Johnny; Chia, Sean; Limbocker, Ryan; Mannini, Benedetta; Ahn, Minkoo; Perni, Michele; Hansson, Oskar; Arosio, Paolo; Kumita, Janet R.; Challa, Pavan Kumar; Cohen, Samuel I. A.; Dobson, Christopher M.; Knowles, Tuomas P. J.; Vendruscolo, Michele


    The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer’s disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as a read-out the changes in the nucleation and elongation rate constants caused by candidate small molecules. We thus identify a pool of compounds that target specific microscopic steps in Aβ42 aggregation. We then test further these small molecules in human cerebrospinal fluid and in a Caenorhabditis elegans model of AD. Our results show that this strategy represents a powerful approach to identify systematically small molecule lead compounds, thus offering an appealing opportunity to reduce the attrition problem in drug discovery. PMID:28011763

  14. Profiling of small RNA cargo of extracellular vesicles shed by Trypanosoma cruzi reveals a specific extracellular signature. (United States)

    Fernandez-Calero, Tamara; Garcia-Silva, Rosa; Pena, Alvaro; Robello, Carlos; Persson, Helena; Rovira, Carlos; Naya, Hugo; Cayota, Alfonso


    Over the last years, an expanding family of small regulatory RNAs (e.g. microRNAs, siRNAs and piRNAs) was recognized as key players in novel forms of post-transcriptional gene regulation in most eukaryotes. However, the machinery associated with Ago/Dicer-dependent small RNA biogenesis was thought to be either entirely lost or extensively simplified in some unicellular organisms including Trypanosoma cruzi, Saccharomyces cerevisiae, Leishmania major and Plasmodium falciparum. Although the biogenesis of small RNAs from non-coding RNAs represent a minor fraction of the normal small RNA transcriptome in eukaryotic cells, they represent the unique small RNA pathways in Trypanosoma cruzi which produce different populations of small RNAs derived from tRNAs, rRNAs, sn/snoRNAs and mRNAs. These small RNAs are secreted included in extracellular vesicles and transferred to other parasites and susceptible mammalian cells. This process represents a novel form of cross-kingdom transfer of genetic material suggesting that secreted vesicles could represent new relevant pieces in life cycle transitions, infectivity and cell-to-cell communication. Here, we provide for the first time a detailed analysis of the small RNA cargo of extracellular vesicles from T. cruzi epimastigotes under nutritional stress conditions compared to the respective intracellular compartment using deep sequencing. Compared with the intracellular compartment, shed extracellular vesicles showed a specific extracellular signature conformed by distinctive patterns of small RNAs derived from rRNA, tRNA, sno/snRNAs and protein coding sequences which evidenced specific secretory small RNA processing pathways.

  15. Comparison of dengue virus type 2-specific small RNAs from RNA interference-competent and -incompetent mosquito cells.

    Directory of Open Access Journals (Sweden)

    Jaclyn C Scott

    Full Text Available The exogenous RNA interference (RNAi pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (siRNAs are key components of this pathway. Understanding the biogenesis of siRNAs in mosquitoes could have important ramifications in using RNAi to control arbovirus transmission. Using deep sequencing technology, we characterized dengue virus type 2 (DENV2-specific small RNAs produced during infection of Aedes aegypti mosquitoes and A. aegypti Aag2 cell cultures and compared them to those produced in the C6/36 Aedes albopictus cell line. We show that the size and mixed polarity of virus-specific small RNAs from DENV-infected A. aegypti cells indicate that they are products of Dicer-2 (Dcr2 cleavage of long dsRNA, whereas C6/36 cells generate DENV2-specific small RNAs that are longer and predominantly positive polarity, suggesting that they originate from a different small RNA pathway. Examination of virus-specific small RNAs after infection of the two mosquito cell lines with the insect-only flavivirus cell fusing agent virus (CFAV corroborated these findings. An in vitro assay also showed that Aag2 A. aegypti cells are capable of siRNA production, while C6/36 A. albopictus cells exhibit inefficient Dcr2 cleavage of long dsRNA. Defective expression or function of Dcr2, the key initiator of the RNAi pathway, might explain the comparatively robust growth of arthropod-borne viruses in the C6/36 cell line, which has been used frequently as a surrogate for studying molecular interactions between arboviruses and cells of their mosquito hosts.

  16. A small RNA activates CFA synthase by isoform-specific mRNA stabilization. (United States)

    Fröhlich, Kathrin Sophie; Papenfort, Kai; Fekete, Agnes; Vogel, Jörg


    Small RNAs use a diversity of well-characterized mechanisms to repress mRNAs, but how they activate gene expression at the mRNA level remains not well understood. The predominant activation mechanism of Hfq-associated small RNAs has been translational control whereby base pairing with the target prevents the formation of an intrinsic inhibitory structure in the mRNA and promotes translation initiation. Here, we report a translation-independent mechanism whereby the small RNA RydC selectively activates the longer of two isoforms of cfa mRNA (encoding cyclopropane fatty acid synthase) in Salmonella enterica. Target activation is achieved through seed pairing of the pseudoknot-exposed, conserved 5' end of RydC to an upstream region of the cfa mRNA. The seed pairing stabilizes the messenger, likely by interfering directly with RNase E-mediated decay in the 5' untranslated region. Intriguingly, this mechanism is generic such that the activation is equally achieved by seed pairing of unrelated small RNAs, suggesting that this mechanism may be utilized in the design of RNA-controlled synthetic circuits. Physiologically, RydC is the first small RNA known to regulate membrane stability.

  17. A distinct mechanism regulating a pollen-specific guanine nucleotide exchange factor for the small GTPase Rop in Arabidopsis thaliana (United States)

    Rop/Rac small GTPases are central to diverse developmental and cellular activities in plants, playing an especially important Role in polar growth of pollen tubes. Although it is established that a class of plant-specific RopGEFs promotes the activity of Rop/Rac through the catalytic PRONE (Plant-sp...

  18. Adult stem cells in the small intestine are intrinsically programmed with their location-specific function

    NARCIS (Netherlands)

    Middendorp, Sabine; Schneeberger, Kerstin; Wiegerinck, Caroline L; Mokry, Michal; Akkerman, Ronald D L; van Wijngaarden, Simone; Clevers, Hans; Nieuwenhuis, Edward E S

    Differentiation and specialization of epithelial cells in the small intestine are regulated in two ways. First, there is differentiation along the crypt-villus axis of the intestinal stem cells into absorptive enterocytes, Paneth, goblet, tuft, enteroendocrine, or M cells, which is mainly regulated

  19. Specific protein homeostatic functions of small heat-shock proteins increase lifespan. (United States)

    Vos, Michel J; Carra, Serena; Kanon, Bart; Bosveld, Floris; Klauke, Karin; Sibon, Ody C M; Kampinga, Harm H


    During aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat-shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress-denatured substrates and/or to prevent aggregation of disease-associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70-dependent refolding of stress-denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70-independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.

  20. Snorc is a novel cartilage specific small membrane proteoglycan expressed in differentiating and articular chondrocytes

    DEFF Research Database (Denmark)

    Heinonen, J; Taipaleenmäki, H; Roering, P;


    -tag was expressed in Cos7 cells, and the cell lysate was studied for putative glycosaminoglycan attachment by digestion with chondroitinase ABC and Western blotting. RESULTS: The predicted molecule is a small, 121 amino acids long type I single-pass transmembrane chondroitin sulfate proteoglycan, that contains ER...

  1. The Strategic Choices of Small Medium-Sized Enterprises Integration: Evidence from Specific Economic Territory

    Directory of Open Access Journals (Sweden)

    Mohsen Brahmi


    Full Text Available The emergence of SMEs was conditioned by institutional and economic factors. These factors, as well as other internal promoted the integration of strategic thinking within this type of business, by adopting suitable strategies. Indeed, our research objective is to determine the extent of adoption of the approach and the strategic decision by the Algerian SMEs, and highlight the characteristics of its strategies through a survey on a sample of SMEs located in the West of the Algeria. The analysis of this empirical study will be preceded by a theoretical overview that aims to show the different concepts of business strategy, and more specifically those of the SMEs, and then to identify the specifics of strategic management within the SME. Finally, we will analyze the survey data basing on graphics to determine the different strategic options available to theses SMEs from the sample according to this specific economic territory.

  2. A Small Aptamer with Strong and Specific Recognition of the Triphosphate of ATP (United States)

    Sazani, Peter L.; Larralde, Rosa


    We report the in vitro selection of an RNA-based ATP aptamer with the ability to discriminate between adenosine ligands based on their 5‘ phosphorylation state. Previous selection of ATP aptamers yielded molecules that do not significantly discriminate between ligands at the 5‘ position. By applying a selective pressure that demands recognition of the 5‘ triphosphate, we obtained an aptamer that binds to ATP with a Kd of approximately 5 μM, and to AMP with a Kd of approximately 5.5 mM, a difference of 1100-fold. This aptamer demonstrates the ability of small RNAs to interact with negatively charged moieties. PMID:15237981

  3. Silencing-associated and meiosis-specific small RNA pathways in Paramecium tetraurelia (United States)

    Lepère, Gersende; Nowacki, Mariusz; Serrano, Vincent; Gout, Jean-François; Guglielmi, Gérard; Duharcourt, Sandra; Meyer, Eric


    Distinct small RNA pathways are involved in the two types of homology-dependent effects described in Paramecium tetraurelia, as shown by a functional analysis of Dicer and Dicer-like genes and by the sequencing of small RNAs. The siRNAs that mediate post-transcriptional gene silencing when cells are fed with double-stranded RNA (dsRNA) were found to comprise two subclasses. DCR1-dependent cleavage of the inducing dsRNA generates ∼23-nt primary siRNAs from both strands, while a different subclass of ∼24-nt RNAs, characterized by a short untemplated poly-A tail, is strictly antisense to the targeted mRNA, suggestive of secondary siRNAs that depend on an RNA-dependent RNA polymerase. An entirely distinct pathway is responsible for homology-dependent regulation of developmental genome rearrangements after sexual reproduction. During early meiosis, the DCL2 and DCL3 genes are required for the production of a highly complex population of ∼25-nt scnRNAs from all types of germline sequences, including both strands of exons, introns, intergenic regions, transposons and Internal Eliminated Sequences. A prominent 5′-UNG signature, and a minor fraction showing the complementary signature at positions 21–23, indicate that scnRNAs are cleaved from dsRNA precursors as duplexes with 2-nt 3′ overhangs at both ends, followed by preferential stabilization of the 5′-UNG strand. PMID:19103667

  4. Specificities of the small and medium-sized enterprises in the Czech Republic and EU

    Directory of Open Access Journals (Sweden)

    Helena Chládková


    Full Text Available Small and medium enterprises (SME are the engine of the European economy. They are an essential source of jobs, create entrepreneurial spirit and innovation in the EU and are thus crucial for fostering competitiveness and employment. In the enlarged European Union of 27 countries, some 20 million SMEs provide around 75 million jobs and represent 99 % of all enterprises. However, they are often confronted with market imperfections. SMEs frequently have difficulties in obtaining capital or credit, particularly in the early start–up phase. Their limited resources may also restrict access to new technology or innovation. It is therefore necessary to monitor the development of SMEs in individual EU countries and highlighting their problems and mainly to their importance.During the recent period of time there have been many researchers from the FBE Mendel University in Brno, who focused on the analysis of the small and medium-sized enterprise, e.g. Bohušová (2007; Chládková (2009; Nerudová a Bohušová (2008; Kubíčková a Peprný (2006; Zrůst a Pyšný (2008. This paper is the part of the Research proposal MSM 6215648904 being solved at the FBE Mendel University in Brno.

  5. Small molecule functional analogs of peptides that inhibit lambda site-specific recombination and bind Holliday junctions. (United States)

    Ranjit, Dev K; Rideout, Marc C; Nefzi, Adel; Ostresh, John M; Pinilla, Clemencia; Segall, Anca M


    Our lab has isolated hexameric peptides that are structure-selective ligands of Holliday junctions (HJ), central intermediates of several DNA recombination reactions. One of the most potent of these inhibitors, WRWYCR, has shown antibacterial activity in part due to its inhibition of DNA repair proteins. To increase the therapeutic potential of these inhibitors, we searched for small molecule inhibitors with similar activities. We screened 11 small molecule libraries comprising over nine million individual compounds and identified a potent N-methyl aminocyclic thiourea inhibitor that also traps HJs formed during site-specific recombination reactions in vitro. This inhibitor binds specifically to protein-free HJs and can inhibit HJ resolution by RecG helicase, but only showed modest growth inhibition of bacterial with a hyperpermeable outer membrane; nonetheless, this is an important step in developing a functional analog of the peptide inhibitors. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Application of photostable quantum dots for indirect immunofluorescent detection of specific bacterial serotypes on small marine animals (United States)

    Decho, Alan W.; Beckman, Erin M.; Chandler, G. Thomas; Kawaguchi, Tomohiro


    An indirect immunofluorescence approach was developed using semiconductor quantum dot nanocrystals to label and detect a specific bacterial serotype of the bacterial human pathogen Vibrio parahaemolyticus, attached to small marine animals (i.e. benthic harpacticoid copepods), which are suspected pathogen carriers. This photostable labeling method using nanotechnology will potentially allow specific serotypes of other bacterial pathogens to be detected with high sensitivity in a range of systems, and can be easily applied for sensitive detection to other Vibrio species such as Vibrio cholerae.

  7. Group-specific small-subunit rRNA hybridization probes to characterize filamentous foaming in activated sludge systems.


    de los Reyes, F L; Ritter, W; Raskin, L.


    Foaming in activated sludge systems is characterized by the formation of a thick, chocolate brown-colored scum that floats on the surface of aeration basins and secondary clarifiers. These viscous foams have been associated with the presence of filamentous mycolic acid-containing actinomycetes. To aid in evaluating the microbial representation in foam, we developed and characterized group-, genus-, and species-specific oligonucleotide probes targeting the small subunit rRNA of the Mycobacteri...

  8. Intra-specific pelage color variation in a South American small rodent species

    Directory of Open Access Journals (Sweden)

    M. L. Sandoval Salinas

    Full Text Available Abstract Intra-specific color variation is often underestimated by researchers, and among mammals, intra-specific differences in coloration are poorly documented for most species. The main goal of this study was to apply an objective color measurement methodology to the study of a specific problem: the detection, if any, of patterns of changes in the fur color of specimens of Akodon budini in relation to biological (i.e., sex and environmental (i.e., season variables. We hypothesize that coat color will be more homogeneous in males than in females and that coat color will be darker in winter than in summer, the latter being orange. We measured the pelage color on five points over the dorsal surface of 26 A. budini museum specimens using a spectroradiometer and a diffuse illumination cabin. We used Principal Component Analysis to describe the association between the color variables, sex and season, and each of the observations. We then used general linear models of Analysis of Variance to examine relationships between color data, season, and sex. The results clearly confirm the hypothesis related to seasonal coat color change but do not directly confirm the hypothesis related to changes in coat color in relation to sex, and we show the complexity of the studied pattern. In conclusion, undoubtedly, the studied variables should accordingly be considered when studying the coloration of specimens for characterization, identification and discrimination of different taxonomic units based on color.

  9. Specificity of insulin signalling in human skeletal muscle as revealed by small interfering RNA. (United States)

    Krook, A; Zierath, J R


    Insulin action on metabolically active tissues is a complex process involving positive and negative feedback regulation to control whole body glucose homeostasis. At the cellular level, glucose and lipid metabolism, as well as protein synthesis, are controlled through canonical insulin signalling cascades. The discovery of small interfering RNA (siRNA) allows for the molecular dissection of critical components of the regulation of metabolic and gene regulatory events in insulin-sensitive tissues. The application of siRNA to tissues of human origin allows for the molecular dissection of the mechanism(s) regulating glucose and lipid metabolism. Penetration of the pathways controlling insulin action in human tissue may aid in discovery efforts to develop diabetes prevention and treatment strategies. This review will focus on the use of siRNA to validate critical regulators controlling insulin action in human skeletal muscle, a key organ important for the control of whole body insulin-mediated glucose uptake and metabolism.

  10. Single-station and Small Source Regions GMPE for Site-specific PSHA (United States)

    Gao, J. C.; Lee, C. T.


    Modern ground motion prediction equations (GMPEs) are based on datasets of ground-motion parameters recorded at multiple stations and different earthquakes in various source regions. This would cause excessive ground-motion variability and lead to overestimate of exceedance probability in probabilistic seismic hazard analysis (PSHA). Recent efforts on decomposition for aleatory and epistemic variabilities and moving of the epistemic uncertainty to logic tree reveal that hazard level remains unchanged. To reduce the epistemic uncertainty so that the total variability is reduced in a GMPE becomes critical in the PSHA. In the present study, a total of 30,602 strong-motion records from TSMIP in Taiwan are selected and used to accomplish the regression analysis of a regional GMPE at the first step. Then, 9 stations in different part of Taiwan, each contains at least 55 records, are selected to complete a single-station GMPE, respectively, at the second step. The results reveal that the sigma of the regional GMPE is 0.626 in ln unit and the sigma of single-station GMPE is ranging 0.416 to 0.567. The single-station sigma is about 9% to 33% reduction from the regional one. At last, source zones are further divided in GMPEs, the sigma of single-station and small source regions GMPEs can be reduced 16% to 36% relative to the regional one. When PSHA is performed by adopting the single-station sigma, the hazard is 11% to 48% smaller then that regional sigma is used. The result of a PSHA may be further reduced, if this single-station to small source region attenuation relationship is used.

  11. Specific and nonspecific B-cell function in the small intestines of patients with Whipple's disease. (United States)

    Geelhaar, Anika; Moos, Verena; Schinnerling, Katina; Allers, Kristina; Loddenkemper, Christoph; Fenollar, Florence; LaScola, Bernard; Raoult, Didier; Schneider, Thomas


    Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection.

  12. Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers. (United States)

    Chopra, Sameer; Liu, Jie; Alemozaffar, Mehrdad; Nichols, Peter W; Aron, Manju; Weisenberger, Daniel J; Collings, Clayton K; Syan, Sumeet; Hu, Brian; Desai, Mihir; Aron, Monish; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning; Siegmund, Kimberly D


    The clinical management of small renal masses (SRMs) is challenging since the current methods for distinguishing between benign masses and malignant renal cell carcinomas (RCCs) are frequently inaccurate or inconclusive. In addition, renal cancer subtypes also have different treatments and outcomes. High false negative rates increase the risk of cancer progression and indeterminate diagnoses result in unnecessary and potentially morbid surgical procedures. We built a predictive classification model for kidney tumors using 697 DNA methylation profiles from six different subgroups: clear cell, papillary and chromophobe RCC, benign angiomylolipomas, oncocytomas, and normal kidney tissues. Furthermore, the DNA methylation-dependent classifier has been validated in 272 ex vivo needle biopsy samples from 100 renal masses (71% SRMs). In general, the results were highly reproducible (89%, n=70) in predicting identical malignant subtypes from biopsies. Overall, 98% of adjacent-normals (n=102) were correctly classified as normal, while 92% of tumors (n=71) were correctly classified malignant and 86% of benign (n=29) were correctly classified benign by this classification model. Overall, this study provides molecular-based support for using routine needle biopsies to determine tumor classification of SRMs and support the clinical decision-making.

  13. A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins. (United States)

    Bellucci, Joseph J; Bhattacharyya, Jayanta; Chilkoti, Ashutosh


    We provide the first demonstration that isopeptide ligation, a noncanonical activity of the enzyme sortase A, can be used to modify recombinant proteins. This reaction was used in vitro to conjugate small molecules to a peptide, an engineered targeting protein, and a full-length monoclonal antibody with an exquisite level of control over the site of conjugation. Attachment to the protein substrate occurred exclusively through isopeptide bonds at a lysine ε-amino group within a specific amino acid sequence. This reaction allows more than one molecule to be site-specifically conjugated to a protein at internal sites, thereby overcoming significant limitations of the canonical native peptide ligation reaction catalyzed by sortase A. Our method provides a unique chemical ligation procedure that is orthogonal to existing methods, supplying a new method to site-specifically modify lysine residues that will be a valuable addition to the protein conjugation toolbox.

  14. Occupational exposure in small and medium scale industry with specific reference to heat and noise. (United States)

    Singh, Lakhwinder Pal; Bhardwaj, Arvind; Deepak, Kishore Kumar


    This study was undertaken to assess heat and noise exposure and occupational safety practices in small and medium scale casting and forging units (SMEs) of Northern India. We conducted personal interviews of 350 male workers of these units through a comprehensive questionnaire and collected information on heat and noise exposure, use of protective equipment, sweat loss and water intake, working hour. The ambient wet bulb globe temperature (WBGT index) was measured using quest temp 34/36o area heat stress monitor. A-weighted Leq ambient noise was measured using a quest sound level meter "ANSI SI. 43-1997 (R 2002) type-1 model SOUNDPRO SE/DL". We also incorporated OSHA norms for hearing conservation which include - an exchange rate of 5dB(A), criterion level at 90dB(A), criterion time of eight hours, threshold level is equal to 80dB(A), upper limit is equal to 140dB(A) and with F/S response rate. Results of the study revealed that occupational heat exposure in melting, casting, forging and punching sections is high compared to ACGIH/NIOSH norms. Ambience noise in various sections like casting / molding, drop forging, cutting presses, punching, grinding and barreling process was found to be more than 90dB(A). About 95% of the workers suffered speech interference where as high noise annoyance was reported by only 20%. Overall, 68% workers were not using any personal protective equipment (PPE). The study concluded that the proportion of SME workers exposed to high level heat stress and noise (60 - 72 hrs/week) is high. The workers engaged in forging and grinding sections are more prone to noise induced hearing loss (NIHL) at higher frequencies as compared to workers of other sections. It is recommended that there is a strong need to implement the standard of working hours as well as heat stress and noise control measures.

  15. Cytotoxic murine monoclonal antibody LAM8 with specificity for human small cell carcinoma of the lung. (United States)

    Stahel, R A; O'Hara, C J; Mabry, M; Waibel, R; Sabbath, K; Speak, J A; Bernal, S D


    The reactivity of the murine immunoglobulin monoclonal antibody LAM8 directed against a membrane antigen of human small cell carcinoma (SCC) of the lung was investigated on human cell lines and tissues. Indirect immunofluorescence staining, radioimmunoassays, and cytotoxicity assays showed LAM8 antibody to selectively react with SCC but not with non-SCC lung cancer cell lines and extrapulmonary tumor cell lines. Unlike other SCC antibodies, including those we have previously described, highly preferential reactivity with SCC tissues was also demonstrated by immunoperoxidase staining of deparaffinized formalin-fixed tissue sections. Membrane and cytoplasmic staining was seen in of 9 of 12 SCC tissues. No significant staining was seen in non-SCC lung cancer and a wide range of other tumors, including mesothelioma and bronchial carcinoids. Significant LAM8 reactivity was also absent in normal tissues of all major organs. Few tumors and epithelial tissues, including bronchial epithelium had rare LAM8 positive cells which were always less than 2% of the entire cell population. In vitro treatment with antibody and human complement was highly cytotoxic to SCC cells, but had not effect on bone marrow progenitor cells. Immunoblotting of membrane extracts separated on sodium dodecyl sulfate-polyacrylamide gels showed the LAM8 antigen to have a band of an approximate molecular weight of 135,000 and a cluster of bands with approximate molecular weights of 90,000. This reactivity was lost after incubation of the extracts with periodate. LAM8 antibody shows a highly preferential reactivity with SCC cell lines and formalin-fixed paraffin-embedded SCC tissues and is selectively cytotoxic to cells expressing LAM8 antigen.

  16. Occupational exposure in small and medium scale industry with specific reference to heat and noise

    Directory of Open Access Journals (Sweden)

    Lakhwinder Pal Singh


    Full Text Available This study was undertaken to assess heat and noise exposure and occupational safety practices in small and medium scale casting and forging units (SMEs of Northern India. We conducted personal interviews of 350 male workers of these units through a comprehensive questionnaire and collected information on heat and noise exposure, use of protective equipment, sweat loss and water intake, working hour. The ambient wet bulb globe temperature (WBGT index was measured using quest temp 34/36o area heat stress monitor. A-weighted Leq ambient noise was measured using a quest sound level meter "ANSI SI. 43-1997 (R 2002 type-1 model SOUNDPRO SE/DL". We also incorporated OSHA norms for hearing conservation which include - an exchange rate of 5dB(A, criterion level at 90dB(A, criterion time of eight hours, threshold level is equal to 80dB(A, upper limit is equal to 140dB(A and with F/S response rate. Results of the study revealed that occupational heat exposure in melting, casting, forging and punching sections is high compared to ACGIH/NIOSH norms. Ambience noise in various sections like casting / molding, drop forging, cutting presses, punching, grinding and barreling process was found to be more than 90dB(A. About 95% of the workers suffered speech interference where as high noise annoyance was reported by only 20%. Overall, 68% workers were not using any personal protective equipment (PPE. The study concluded that the proportion of SME workers exposed to high level heat stress and noise (60 - 72 hrs/week is high. The workers engaged in forging and grinding sections are more prone to noise induced hearing loss (NIHL at higher frequencies as compared to workers of other sections. It is recommended that there is a strong need to implement the standard of working hours as well as heat stress and noise control measures.

  17. Group-specific small-subunit rRNA hybridization probes to characterize filamentous foaming in activated sludge systems. (United States)

    de los Reyes, F L; Ritter, W; Raskin, L


    Foaming in activated sludge systems is characterized by the formation of a thick, chocolate brown-colored scum that floats on the surface of aeration basins and secondary clarifiers. These viscous foams have been associated with the presence of filamentous mycolic acid-containing actinomycetes. To aid in evaluating the microbial representation in foam, we developed and characterized group-, genus-, and species-specific oligonucleotide probes targeting the small subunit rRNA of the Mycobacterium complex, Gordona spp., and Gordona (Nocardia) amarae, respectively. The use of a universal base analog, 5-nitroindole, in oligonucleotide probe design was evaluated by comparing the characteristics of two different versions of the Mycobacterium complex probe. The temperature of dissociation of each probe was determined. Probe specificity studies with a diverse collection of 67 target and nontarget rRNAs demonstrated the specificity of the probes to the target groups. Whole-cell hybridizations with fluorescein- and rhodamine-labeled probes were performed with pure cultures of various members of the Mycobacterium complex as well as with environmental samples from a full-scale activated sludge plant which experienced foaming. Quantitative membrane hybridizations with activated sludge and anaerobic digester foam showed that 15.0 to 18.3% of the total small-subunit rRNAs could be attributed to members of the Mycobacterium complex, of which a vast majority consisted of Gordona rRNA. Several G. amarae strains made up only a very small percentage of the Gordona strains present. We demonstrated that group-specific rRNA probes are useful tools for the in situ monitoring and identification of filamentous bacteria in activated sludge systems.

  18. Tissue-specific expression and cDNA cloning of small nuclear ribonucleoprotein-associated polypeptide N

    Energy Technology Data Exchange (ETDEWEB)

    McAllister, G.; Amara, S.G.; Lerner, M.R. (Yale Univ. School of Medicine, New Haven, CT (USA))


    Sera from some patients with systemic lupus erythematosus and other autoimmune diseases have antibodies against nuclear antigens. An example is anti-Sm sera, which recognize proteins associated with small nuclear RNA molecules (small nuclear ribonucleoprotein (snRNP) particles). In this paper anti-Sm sera were used to probe immunoblots of various rat tissues. A previously unidentified M{sub r} 28,000 polypeptide was recognized by these anti-Sm sera. This polypeptide, referred to as N, is expressed in a tissue-specific manner, being most abundant in rat brain, less so in heart, and undetectable in the other tissues examined. Immunoprecipitation experiments using antibodies directed against the cap structure of small nuclear RNAs have demonstrated that N is a snRNP-associated polypeptide. Anti-Sm serum was also used to isolate a partial cDNA clone ({lambda}rb91) from a rat brain phage {lambda}gt11 cDNA expression library. A longer cDNA clone was obtained by rescreening the library with {lambda}rb91. In vitro transcription and subsequent translation of this subcloned, longer insert (pGMA2) resulted in a protein product with the same electrophoretic and immunological properties as N, confirming that pGMA2 encodes N. The tissue distribution of N and the involvement of snRNP particles in nuclear pre-mRNA processing may imply a role for N in tissue-specific pre-mRNA splicing.

  19. The synthetic genetic interaction network reveals small molecules that target specific pathways in Sacchromyces cerevisiae. (United States)

    Tamble, Craig M; St Onge, Robert P; Giaever, Guri; Nislow, Corey; Williams, Alexander G; Stuart, Joshua M; Lokey, R Scott


    High-throughput elucidation of synthetic genetic interactions (SGIs) has contributed to a systems-level understanding of genetic robustness and fault-tolerance encoded in the genome. Pathway targets of various compounds have been predicted by comparing chemical-genetic synthetic interactions to a network of SGIs. We demonstrate that the SGI network can also be used in a powerful reverse pathway-to-drug approach for identifying compounds that target specific pathways of interest. Using the SGI network, the method identifies an indicator gene that may serve as a good candidate for screening a library of compounds. The indicator gene is selected so that compounds found to produce sensitivity in mutants deleted for the indicator gene are likely to abrogate the target pathway. We tested the utility of the SGI network for pathway-to-drug discovery using the DNA damage checkpoint as the target pathway. An analysis of the compendium of synthetic lethal interactions in yeast showed that superoxide dismutase 1 (SOD1) has significant SGI connectivity with a large subset of DNA damage checkpoint and repair (DDCR) genes in Saccharomyces cerevisiae, and minimal SGIs with non-DDCR genes. We screened a sod1Δ strain against three National Cancer Institute (NCI) compound libraries using a soft agar high-throughput halo assay. Fifteen compounds out of ∼3100 screened showed selective toxicity toward sod1Δ relative to the isogenic wild type (wt) strain. One of these, 1A08, caused a transient increase in growth in the presence of sublethal doses of DNA damaging agents, suggesting that 1A08 inhibits DDCR signaling in yeast. Genome-wide screening of 1A08 against the library of viable homozygous deletion mutants further supported DDCR as the relevant targeted pathway of 1A08. When assayed in human HCT-116 colorectal cancer cells, 1A08 caused DNA-damage resistant DNA synthesis and blocked the DNA-damage checkpoint selectively in S-phase.

  20. Methodology for Training Small Domain-specific Language Models and Its Application in Service Robot Speech Interface

    Directory of Open Access Journals (Sweden)

    ONDAS Stanislav


    Full Text Available The proposed paper introduces the novel methodology for training small domain-specific language models only from domain vocabulary. Proposed methodology is intended for situations, when no training data are available and preparing of appropriate deterministic grammar is not trivial task. Methodology consists of two phases. In the first phase the “random” deterministic grammar, which enables to generate all possible combination of unigrams and bigrams is constructed from vocabulary. Then, prepared random grammar serves for generating the training corpus. The “random” n-gram model is trained from generated corpus, which can be adapted in second phase. Evaluation of proposed approach has shown usability of the methodology for small domains. Results of methodology assessment favor designed method instead of constructing the appropriate deterministic grammar.

  1. Structural Comparison, Substrate Specificity, and Inhibitor Binding of AGPase Small Subunit from Monocot and Dicot: Present Insight and Future Potential

    Directory of Open Access Journals (Sweden)

    Kishore Sarma


    Full Text Available ADP-glucose pyrophosphorylase (AGPase is the first rate limiting enzyme of starch biosynthesis pathway and has been exploited as the target for greater starch yield in several plants. The structure-function analysis and substrate binding specificity of AGPase have provided enormous potential for understanding the role of specific amino acid or motifs responsible for allosteric regulation and catalytic mechanisms, which facilitate the engineering of AGPases. We report the three-dimensional structure, substrate, and inhibitor binding specificity of AGPase small subunit from different monocot and dicot crop plants. Both monocot and dicot subunits were found to exploit similar interactions with the substrate and inhibitor molecule as in the case of their closest homologue potato tuber AGPase small subunit. Comparative sequence and structural analysis followed by molecular docking and electrostatic surface potential analysis reveal that rearrangements of secondary structure elements, substrate, and inhibitor binding residues are strongly conserved and follow common folding pattern and orientation within monocot and dicot displaying a similar mode of allosteric regulation and catalytic mechanism. The results from this study along with site-directed mutagenesis complemented by molecular dynamics simulation will shed more light on increasing the starch content of crop plants to ensure the food security worldwide.

  2. A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown

    DEFF Research Database (Denmark)

    Higgins, Geoff S; Prevo, Remko; Lee, Yin-Fai


    radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B...... polymerase ) as a potential tumor-specific target. Subsequent investigations showed that POLQ knockdown resulted in radiosensitization of a panel of tumor cell lines from different primary sites while having little or no effect on normal tissue cell lines. These findings raise the possibility that POLQ...

  3. Sex-Specific Metabolic Outcomes in Offspring of Female Rats Born Small or Exposed to Stress During Pregnancy. (United States)

    Cheong, Jean N; Cuffe, James S M; Jefferies, Andrew J; Anevska, Kristina; Moritz, Karen M; Wlodek, Mary E


    Low birth weight increases adult metabolic disease risk in both the first (F1) and second (F2) generation. Physiological stress during pregnancy in F1 females that were born small induces F2 fetal growth restriction, but the long-term metabolic health of these F2 offspring is unknown. Uteroplacental insufficiency (restricted) or sham (control) surgery was performed in F0 rats. F1 females (control, restricted) were allocated to unstressed or stressed pregnancies. F2 offspring exposed to maternal stress in utero had reduced birth weight. At 6 months, F2 stressed males had elevated fasting glucose. In contrast, F2 restricted males had reduced pancreatic β-cell mass. Interestingly, these metabolic deficits were not present at 12 month. F2 males had increased adrenal mRNA expression of steroidogenic acute regulatory protein and IGF-1 receptor when their mothers were born small or exposed to stress during pregnancy. Stressed control F2 males had increased expression of adrenal genes that regulate androgen signaling at 6 months, whereas expression increased in restricted male and female offspring at 12 months. F2 females from stressed mothers had lower area under the glucose curve during glucose tolerance testing at 12 months compared with unstressed females but were otherwise unaffected. If F1 mothers were either born small or exposed to stress during her pregnancy, F2 offspring had impaired physiological outcomes in a sex- and age-specific manner. Importantly, stress during pregnancy did not exacerbate disease risk in F2 offspring of mothers born small, suggesting that they independently program disease in offspring through different mechanisms.

  4. A Feasibility Study of a Field-specific Weather Service for Small-scale Farms in a Topographically Complex Watershed (United States)

    Kim, S. O.; Shim, K. M.; Shin, Y. S.; Yun, J. I.


    Adequate downscaling of synoptic forecasts is a prerequisite for improved agrometeorological service to rural areas in South Korea where complex terrain and small farms are common. Geospatial schemes based on topoclimatology were used to scale down the Korea Meteorological Administration (KMA) temperature forecasts to the local scale (~30 m) across a rural catchment. Local temperatures were estimated at 14 validation sites at 0600 and 1500 LST in 2013/2014 using these schemes and were compared with observations. A substantial reduction in the estimation error was found for both 0600 and 1500 temperatures compared with uncorrected KMA products. Improvement was most remarkable at low lying locations for the 0600 temperature and at the locations on west- and south-facing slopes for the 1500 temperature. Using the downscaled real-time temperature data, a pilot service has started to provide field-specific weather information tailored to meet the requirements of small-scale farms. For example, the service system makes a daily outlook on the phenology of crop species grown in a given field using the field-specific temperature data. When the temperature forecast is given for tomorrow morning, a frost risk index is calculated according to a known phenology-frost injury relationship. If the calculated index is higher than a pre-defined threshold, a warning is issued and delivered to the grower's cellular phone with relevant countermeasures to help protect crops against frost damage. The system was implemented for a topographically complex catchment of 350km2with diverse agricultural activities, and more than 400 volunteer farmers are participating in this pilot service to access user-specific weather information.

  5. Isoform-specific monobody inhibitors of small ubiquitin-related modifiers engineered using structure-guided library design. (United States)

    Gilbreth, Ryan N; Truong, Khue; Madu, Ikenna; Koide, Akiko; Wojcik, John B; Li, Nan-Sheng; Piccirilli, Joseph A; Chen, Yuan; Koide, Shohei


    Discriminating closely related molecules remains a major challenge in the engineering of binding proteins and inhibitors. Here we report the development of highly selective inhibitors of small ubiquitin-related modifier (SUMO) family proteins. SUMOylation is involved in the regulation of diverse cellular processes. Functional differences between two major SUMO isoforms in humans, SUMO1 and SUMO2/3, are thought to arise from distinct interactions mediated by each isoform with other proteins containing SUMO-interacting motifs (SIMs). However, the roles of such isoform-specific interactions are largely uncharacterized due in part to the difficulty in generating high-affinity, isoform-specific inhibitors of SUMO/SIM interactions. We first determined the crystal structure of a "monobody," a designed binding protein based on the fibronectin type III scaffold, bound to the yeast homolog of SUMO. This structure illustrated a mechanism by which monobodies bind to the highly conserved SIM-binding site while discriminating individual SUMO isoforms. Based on this structure, we designed a SUMO-targeted library from which we obtained monobodies that bound to the SIM-binding site of human SUMO1 with K(d) values of approximately 100 nM but bound to SUMO2 400 times more weakly. The monobodies inhibited SUMO1/SIM interactions and, unexpectedly, also inhibited SUMO1 conjugation. These high-affinity and isoform-specific inhibitors will enhance mechanistic and cellular investigations of SUMO biology.

  6. Isoform-specific monobody inhibitors of small ubiquitin-related modifiers engineered using structure-guided library design

    Energy Technology Data Exchange (ETDEWEB)

    Gilbreth, Ryan N.; Truong, Khue; Madu, Ikenna; Koide, Akiko; Wojcik, John B.; Li, Nan-Sheng; Piccirilli, Joseph A.; Chen, Yuan; Koide, Shohei (UC); (CHNMC)


    Discriminating closely related molecules remains a major challenge in the engineering of binding proteins and inhibitors. Here we report the development of highly selective inhibitors of small ubiquitin-related modifier (SUMO) family proteins. SUMOylation is involved in the regulation of diverse cellular processes. Functional differences between two major SUMO isoforms in humans, SUMO1 and SUMO2/3, are thought to arise from distinct interactions mediated by each isoform with other proteins containing SUMO-interacting motifs (SIMs). However, the roles of such isoform-specific interactions are largely uncharacterized due in part to the difficulty in generating high-affinity, isoform-specific inhibitors of SUMO/SIM interactions. We first determined the crystal structure of a 'monobody,' a designed binding protein based on the fibronectin type III scaffold, bound to the yeast homolog of SUMO. This structure illustrated a mechanism by which monobodies bind to the highly conserved SIM-binding site while discriminating individual SUMO isoforms. Based on this structure, we designed a SUMO-targeted library from which we obtained monobodies that bound to the SIM-binding site of human SUMO1 with K{sub d} values of approximately 100 nM but bound to SUMO2 400 times more weakly. The monobodies inhibited SUMO1/SIM interactions and, unexpectedly, also inhibited SUMO1 conjugation. These high-affinity and isoform-specific inhibitors will enhance mechanistic and cellular investigations of SUMO biology.

  7. Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells. (United States)

    Trembley, Janeen H; Unger, Gretchen M; Korman, Vicci L; Tobolt, Diane K; Kazimierczuk, Zygmunt; Pinna, Lorenzo A; Kren, Betsy T; Ahmed, Khalil


    CK2, a pleiotropic Ser/Thr kinase, is an important target for cancer therapy. We tested our novel tenfibgen-based nanocapsule for delivery of the inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and an siRNA directed against both CK2α and α' catalytic subunits to prostate cancer cells. We present data on the TBG nanocapsule itself and on CK2 inhibition or downregulation in treated cells, including effects on Nuclear Factor-kappa B (NF-κB) p65. By direct comparison of two CK2-directed cargos, our data provide proof that the TBG encapsulation design for delivery of drugs specifically to cancer cells has strong potential for small molecule- and nucleic acid-based cancer therapy.

  8. Differential representation of sunflower ESTs in enriched organ-specific cDNA libraries in a small scale sequencing project

    Directory of Open Access Journals (Sweden)

    Heinz Ruth A


    Full Text Available Abstract Background Subtractive hybridization methods are valuable tools for identifying differentially regulated genes in a given tissue avoiding redundant sequencing of clones representing the same expressed genes, maximizing detection of low abundant transcripts and thus, affecting the efficiency and cost effectiveness of small scale cDNA sequencing projects aimed to the specific identification of useful genes for breeding purposes. The objective of this work is to evaluate alternative strategies to high-throughput sequencing projects for the identification of novel genes differentially expressed in sunflower as a source of organ-specific genetic markers that can be functionally associated to important traits. Results Differential organ-specific ESTs were generated from leaf, stem, root and flower bud at two developmental stages (R1 and R4. The use of different sources of RNA as tester and driver cDNA for the construction of differential libraries was evaluated as a tool for detection of rare or low abundant transcripts. Organ-specificity ranged from 75 to 100% of non-redundant sequences in the different cDNA libraries. Sequence redundancy varied according to the target and driver cDNA used in each case. The R4 flower cDNA library was the less redundant library with 62% of unique sequences. Out of a total of 919 sequences that were edited and annotated, 318 were non-redundant sequences. Comparison against sequences in public databases showed that 60% of non-redundant sequences showed significant similarity to known sequences. The number of predicted novel genes varied among the different cDNA libraries, ranging from 56% in the R4 flower to 16 % in the R1 flower bud library. Comparison with sunflower ESTs on public databases showed that 197 of non-redundant sequences (60% did not exhibit significant similarity to previously reported sunflower ESTs. This approach helped to successfully isolate a significant number of new reported sequences

  9. Microplate-based assay for identifying small molecules that bind a specific intersubunit interface within the assembled HIV-1 capsid. (United States)

    Halambage, Upul D; Wong, Jason P; Melancon, Bruce J; Lindsley, Craig W; Aiken, Christopher


    Despite the availability of >30 effective drugs for managing HIV-1 infection, no current therapy is curative, and long-term management is challenging owing to the emergence and spread of drug-resistant mutants. Identification of drugs against novel HIV-1 targets would expand the current treatment options and help to control resistance. The highly conserved HIV-1 capsid protein represents an attractive target because of its multiple roles in replication of the virus. However, the low antiviral potencies of the reported HIV-1 capsid-targeting inhibitors render them unattractive for therapeutic development. To facilitate the identification of more-potent HIV-1 capsid inhibitors, we developed a scintillation proximity assay to screen for small molecules that target a biologically active and specific intersubunit interface in the HIV-1 capsid. The assay, which is based on competitive displacement of a known capsid-binding small-molecule inhibitor, exhibited a signal-to-noise ratio of >9 and a Z factor of >0.8. In a pilot screen of a chemical library containing 2,400 druglike compounds, we obtained a hit rate of 1.8%. This assay has properties that are suitable for screening large compound libraries to identify novel HIV-1 capsid ligands with antiviral activity.

  10. Interaction of structure-specific and promiscuous G-protein-coupled receptors mediates small-molecule signaling in Caenorhabditis elegans. (United States)

    Park, Donha; O'Doherty, Inish; Somvanshi, Rishi K; Bethke, Axel; Schroeder, Frank C; Kumar, Ujendra; Riddle, Donald L


    A chemically diverse family of small-molecule signals, the ascarosides, control developmental diapause (dauer), olfactory learning, and social behaviors of the nematode model organism, Caenorhabditis elegans. The ascarosides act upstream of conserved signaling pathways, including the insulin, TGF-β, serotonin, and guanylyl cyclase pathways; however, the sensory processes underlying ascaroside function are poorly understood. Because ascarosides often are multifunctional and show strongly synergistic effects, characterization of their receptors will be essential for understanding ascaroside biology and may provide insight into molecular mechanisms that produce synergistic outcomes in small-molecule sensing. Based on DAF-8 immunoprecipitation, we here identify two G-protein-coupled receptors, DAF-37 and DAF-38, which cooperatively mediate ascaroside perception. daf-37 mutants are defective in all responses to ascr#2, one of the most potent dauer-inducing ascarosides, although this mutant responds normally to other ascarosides. In contrast, daf-38 mutants are partially defective in responses to several different ascarosides. Through cell-specific overexpression, we show that DAF-37 regulates dauer when expressed in ASI neurons and adult behavior when expressed in ASK neurons. Using a photoaffinity-labeled ascr#2 probe and amplified luminescence assays (AlphaScreen), we demonstrate that ascr#2 binds to DAF-37. Photobleaching fluorescent energy transfer assays revealed that DAF-37 and DAF-38 form heterodimers, and we show that heterodimerization strongly increases cAMP inhibition in response to ascr#2. These results suggest that that the ascarosides' intricate signaling properties result in part from the interaction of highly structure-specific G-protein-coupled receptors such as DAF-37 with more promiscuous G-protein-coupled receptors such as DAF-38.

  11. Interaction of structure-specific and promiscuous G-protein–coupled receptors mediates small-molecule signaling in Caenorhabditis elegans (United States)

    Park, Donha; O'Doherty, Inish; Somvanshi, Rishi K.; Bethke, Axel; Schroeder, Frank C.; Kumar, Ujendra; Riddle, Donald L.


    A chemically diverse family of small-molecule signals, the ascarosides, control developmental diapause (dauer), olfactory learning, and social behaviors of the nematode model organism, Caenorhabditis elegans. The ascarosides act upstream of conserved signaling pathways, including the insulin, TGF-β, serotonin, and guanylyl cyclase pathways; however, the sensory processes underlying ascaroside function are poorly understood. Because ascarosides often are multifunctional and show strongly synergistic effects, characterization of their receptors will be essential for understanding ascaroside biology and may provide insight into molecular mechanisms that produce synergistic outcomes in small-molecule sensing. Based on DAF-8 immunoprecipitation, we here identify two G-protein–coupled receptors, DAF-37 and DAF-38, which cooperatively mediate ascaroside perception. daf-37 mutants are defective in all responses to ascr#2, one of the most potent dauer-inducing ascarosides, although this mutant responds normally to other ascarosides. In contrast, daf-38 mutants are partially defective in responses to several different ascarosides. Through cell-specific overexpression, we show that DAF-37 regulates dauer when expressed in ASI neurons and adult behavior when expressed in ASK neurons. Using a photoaffinity-labeled ascr#2 probe and amplified luminescence assays (AlphaScreen), we demonstrate that ascr#2 binds to DAF-37. Photobleaching fluorescent energy transfer assays revealed that DAF-37 and DAF-38 form heterodimers, and we show that heterodimerization strongly increases cAMP inhibition in response to ascr#2. These results suggest that that the ascarosides' intricate signaling properties result in part from the interaction of highly structure-specific G-protein–coupled receptors such as DAF-37 with more promiscuous G-protein–coupled receptors such as DAF-38. PMID:22665789

  12. Pharmacokinetic and Biodistribution Assessment of a Near Infrared-Labeled PSMA-Specific Small Molecule in Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Joy L. Kovar


    Full Text Available Prostate cancer is the most frequently diagnosed cancer in men and often requires surgery. Use of near infrared (NIR technologies to perform image-guided surgery may improve accurate delineation of tumor margins. To facilitate preclinical testing of such outcomes, here we developed and characterized a PSMA-targeted small molecule, YC-27. IRDye 800CW was conjugated to YC-27 or an anti-PSMA antibody used for reference. Human 22Rv1, PC3M-LN4, and/or LNCaP prostate tumor cells were exposed to the labeled compounds. In vivo targeting and clearance properties were determined in tumor-bearing mice. Organs and tumors were excised and imaged to assess probe localization. YC-27 exhibited a dose dependent increase in signal upon binding. Binding specificity and internalization were visualized by microscopy. In vitro and in vivo blocking studies confirmed YC-27 specificity. In vivo, YC-27 showed good tumor delineation and tissue contrast at doses as low as 0.25 nmole. YC-27 was cleared via the kidneys but bound the proximal tubules of the renal cortex and epididymis. Since PSMA is also broadly expressed on the neovasculature of most tumors, we expect YC-27 will have clinical utility for image-guided surgery and tumor resections.

  13. Habitat-specific bioaccumulation of methylmercury in invertebrates of small mid-latitude lakes in North America

    Energy Technology Data Exchange (ETDEWEB)

    Chetelat, John, E-mail: john.chetelat@ec.gc.c [Groupe de recherche interuniversitaire en limnologie, Departement de sciences biologiques, Universite de Montreal, Montreal, Quebec H3C 3J7 (Canada); Amyot, Marc; Garcia, Edenise [Groupe de recherche interuniversitaire en limnologie, Departement de sciences biologiques, Universite de Montreal, Montreal, Quebec H3C 3J7 (Canada)


    We examined habitat-specific bioaccumulation of methylmercury (MeHg) in aquatic food webs by comparing concentrations in pelagic zooplankton to those in littoral macroinvertebrates from 52 mid-latitude lakes in North America. Invertebrate MeHg concentrations were primarily correlated with water pH, and after controlling for this influence, pelagic zooplankton had significantly higher MeHg concentrations than littoral primary consumers but lower MeHg than littoral secondary consumers. Littoral primary consumers and pelagic zooplankton are two dominant prey for fish, and greater MeHg in zooplankton is likely sufficient to increase bioaccumulation in pelagic feeders. Intensive sampling of 8 lakes indicated that habitat-specific bioaccumulation in invertebrates (of similar trophic level) may result from spatial variation in aqueous MeHg concentration or from more efficient uptake of aqueous MeHg into the pelagic food web. Our findings demonstrate that littoral-pelagic differences in MeHg bioaccumulation are widespread in small mid-latitude lakes. - Methylmercury levels in dominant invertebrate prey for fish differ between littoral and pelagic habitats within a lake.

  14. Assessing specific oligonucleotides and small molecule antibiotics for the ability to inhibit the CRD-BP-CD44 RNA interaction.

    Directory of Open Access Journals (Sweden)

    Dustin T King

    Full Text Available Studies on Coding Region Determinant-Binding Protein (CRD-BP and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3'UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862-3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862-3055, only three antisense oligonucleotides (DD4, DD7 and DD10 were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions.

  15. Recurrence of mediastinal node cancer after lobe-specific systematic nodal dissection for non-small-cell lung cancer. (United States)

    Maniwa, Tomohiro; Okumura, Takehiro; Isaka, Mitsuhiro; Nakagawa, Kazuo; Ohde, Yasuhisa; Kondo, Haruhiko


    The standard surgical treatment for patients with non-small-cell lung cancer (NSCLC) is lobectomy with systematic nodal dissection (SND). Lobe-specific patterns of nodal metastases have been recognized, and lobe-specific SND (L-SND) has been reported. We performed L-SND depending on patient-related factors, such as age or the presence of diabetes or respiratory dysfunction, or in the context of specific tumour-related factors, such as the presence of a tumour with a wide area of ground-glass opacity. Between September 2002 and December 2008, 335 consecutive patients with clinical and intraoperative N0 NSCLC underwent curative lobectomies at Shizuoka Cancer Center Hospital. Among these 335 patients, 206 underwent SND (Group A) and 129 underwent L-SND. Of the 129 patients undergoing L-SND, 98 underwent L-SND due to patient-related factors (Group B) and 31 underwent L-SND due to tumour-related factors (Group C). There were no significant differences in morbidity or blood loss between patients undergoing SND or L-SND, but there was a significant difference in the mean operative times. The 5-year disease-free survival (5-DFS) and 5-year overall survival (5-OS) of patients in Group C were 100%. Although the patients in Group B showed no significant difference in 5-DFS and 5-OS compared with Group A, patients in Group B had significantly more initial recurrence of mediastinal node cancer than did the Group A patients (P = 0.0050). The recurrence of mediastinal node cancer in patients undergoing L-SND was significantly greater than that in those undergoing SND.

  16. Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Tao Cui

    Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

  17. Cellular cross talk in the small intestinal mucosa: postnatal lymphocytic immigration elicits a specific epithelial transcriptional response

    DEFF Research Database (Denmark)

    Schjoldager, Katrine Ter-Borch Gram; Maltesen, Henrik R; Balmer, Sophie;


    such physiological cross talk between the immune system and the epithelium in the postnatal small intestinal mucosa is lacking. We have investigated the transcriptome changes occurring in the postnatal mouse small intestine using DNA microarray technology, immunocytochemistry, and quantitative real-time RT...... migration into the small intestinal mucosa....

  18. Physiological outflow boundary conditions methodology for small arteries with multiple outlets: a patient-specific hepatic artery haemodynamics case study. (United States)

    Aramburu, Jorge; Antón, Raúl; Bernal, Nebai; Rivas, Alejandro; Ramos, Juan Carlos; Sangro, Bruno; Bilbao, José Ignacio


    Physiological outflow boundary conditions are necessary to carry out computational fluid dynamics simulations that reliably represent the blood flow through arteries. When dealing with complex three-dimensional trees of small arteries, and therefore with multiple outlets, the robustness and speed of convergence are also important. This study derives physiological outflow boundary conditions for cases in which the physiological values at those outlets are not known (neither in vivo measurements nor literature-based values are available) and in which the tree exhibits symmetry to some extent. The inputs of the methodology are the three-dimensional domain and the flow rate waveform and the systolic and diastolic pressures at the inlet. The derived physiological outflow boundary conditions, which are a physiological pressure waveform for each outlet, are based on the results of a zero-dimensional model simulation. The methodology assumes symmetrical branching and is able to tackle the flow distribution problem when the domain outlets are at branches with a different number of upstream bifurcations. The methodology is applied to a group of patient-specific arteries in the liver. The methodology is considered to be valid because the pulsatile computational fluid dynamics simulation with the inflow flow rate waveform (input of the methodology) and the derived outflow boundary conditions lead to physiological results, that is, the resulting systolic and diastolic pressures at the inlet match the inputs of the methodology, and the flow split is also physiological.

  19. Antiviral activity of Small interfering RNAs: Specificity testing using heterologous virus reveals interferon-related effects overlooked by conventional mismatch controls

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Lorenzen, Niels; Pedersen, Finn Skou


    RNA interference by small interfering RNAs (siRNAs) is considered to be a highly specific method for knockdown of gene expression in eukaryotic cells via degradation of target mRNA. Mutated siRNA molecules with 1–4 mismatching nucleotides compared to the target mRNA are regularly used as specific...

  20. Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment

    Directory of Open Access Journals (Sweden)

    Yuan Fei


    Full Text Available Abstract Background In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model, or log-normal survival analysis. Methods Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS. DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. Results The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0–2% at 1 year, 0–12% at 3 years, and 0–1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10–12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1–6% at 1 year, 15–26% at 3 years, and 0–12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. Conclusion Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the

  1. Small RNA Library Cloning Procedure for Deep Sequencing of Specific Endogenous siRNA Classes in Caenorhabditis elegans (United States)

    Ow, Maria C.; Lau, Nelson C.; Hall, Sarah E.


    In recent years, distinct classes of small RNAs ranging in size from ~21 to 26 nucleotides have been discovered and shown to play important roles in a wide array of cellular functions. Because of the abundance of these small RNAs, library preparation from an RNA sample followed by deep sequencing provides the identity and quantity of a particular class of small RNAs. In this chapter we describe a detailed protocol for preparing small RNA libraries for deep sequencing on the Illumina platform from the nematode C. elegans. PMID:24920360

  2. BAC CGH-array identified specific small-scale genomic imbalances in diploid DMBA-induced rat mammary tumors

    Directory of Open Access Journals (Sweden)

    Samuelson Emma


    Full Text Available Abstract Background Development of breast cancer is a multistage process influenced by hormonal and environmental factors as well as by genetic background. The search for genes underlying this malignancy has recently been highly productive, but the etiology behind this complex disease is still not understood. In studies using animal cancer models, heterogeneity of the genetic background and environmental factors is reduced and thus analysis and identification of genetic aberrations in tumors may become easier. To identify chromosomal regions potentially involved in the initiation and progression of mammary cancer, in the present work we subjected a subset of experimental mammary tumors to cytogenetic and molecular genetic analysis. Methods Mammary tumors were induced with DMBA (7,12-dimethylbenz[a]anthrazene in female rats from the susceptible SPRD-Cu3 strain and from crosses and backcrosses between this strain and the resistant WKY strain. We first produced a general overview of chromosomal aberrations in the tumors using conventional kartyotyping (G-banding and Comparative Genome Hybridization (CGH analyses. Particular chromosomal changes were then analyzed in more details using an in-house developed BAC (bacterial artificial chromosome CGH-array platform. Results Tumors appeared to be diploid by conventional karyotyping, however several sub-microscopic chromosome gains or losses in the tumor material were identified by BAC CGH-array analysis. An oncogenetic tree analysis based on the BAC CGH-array data suggested gain of rat chromosome (RNO band 12q11, loss of RNO5q32 or RNO6q21 as the earliest events in the development of these mammary tumors. Conclusions Some of the identified changes appear to be more specific for DMBA-induced mammary tumors and some are similar to those previously reported in ACI rat model for estradiol-induced mammary tumors. The later group of changes is more interesting, since they may represent anomalies that involve

  3. Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration

    NARCIS (Netherlands)

    M. Verburg (Melissa); I.B. Renes (Ingrid); D.J. van Nispen; S. Ferdinandusse; M. Jorritsma; H.A. Büller (Hans); A.W.C. Einerhand (Sandra); J. Dekker (Jan)


    textabstractThe rapidly dividing small intestinal epithelium is very sensitive to the cytostatic drug methotrexate. We investigated the regulation of epithelial gene expression in rat jejunum during methotrexate-induced damage and regeneration. Ten differentiation markers were loca

  4. Detector to detector corrections: a comprehensive experimental study of detector specific correction factors for beam output measurements for small radiotherapy beams

    DEFF Research Database (Denmark)

    Azangwe, Godfrey; Grochowska, Paulina; Georg, Dietmar


    Purpose: The aim of the present study is to provide a comprehensive set of detector specific correction factors for beam output measurements for small beams, for a wide range of real time and passive detectors. The detector specific correction factors determined in this study may be potentially u...... measurements, the authors recommend the use of detectors that require relatively little correction, such as unshielded diodes, diamond detectors or microchambers, and solid state detectors such as alanine, TLD, Al2O3:C, or scintillators.......Purpose: The aim of the present study is to provide a comprehensive set of detector specific correction factors for beam output measurements for small beams, for a wide range of real time and passive detectors. The detector specific correction factors determined in this study may be potentially...... useful as a reference data set for small beam dosimetry measurements. Methods: Dose response of passive and real time detectors was investigated for small field sizes shaped with a micromultileaf collimator ranging from 0.6 × 0.6 cm2 to 4.2 × 4.2 cm2 and the measurements were extended to larger fields...

  5. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P


    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  6. Dynamics of speckles with a small number of scattering events: specific features of manifestation of the Doppler effect. (United States)

    Ulyanov, Sergey S


    Spectra of intensity fluctuations of dynamic non-Gaussian speckles formed with a small number of scattering events have been studied theoretically and experimentally. A new type of manifestation of the Doppler effect has been observed. The dependence of frequency position of the Doppler peak and the shape of the Doppler spectrum on the number of scatterers has been analyzed.

  7. Transglutaminase 2-specific coeliac disease autoantibodies induce morphological changes and signs of inflammation in the small-bowel mucosa of mice. (United States)

    Kalliokoski, Suvi; Piqueras, Victoria Ortín; Frías, Rafael; Sulic, Ana-Marija; Määttä, Juha A E; Kähkönen, Niklas; Viiri, Keijo; Huhtala, Heini; Pasternack, Arja; Laurila, Kaija; Sblattero, Daniele; Korponay-Szabó, Ilma R; Mäki, Markku; Caja, Sergio; Kaukinen, Katri; Lindfors, Katri


    Coeliac disease is hallmarked by an abnormal immune reaction against ingested wheat-, rye- and barley-derived gluten and the presence of transglutaminase 2 (TG2)-targeted autoantibodies. The small-bowel mucosal damage characteristic of the disorder develops gradually from normal villus morphology to inflammation and finally to villus atrophy with crypt hyperplasia. Patients with early-stage coeliac disease have TG2-autoantibodies present in serum and small-intestinal mucosa and they may already suffer from abdominal symptoms before the development of villus atrophy. Previously, we have shown that intraperitoneal injections of coeliac patient-derived sera or purified immunoglobulin fraction into mice induce a condition mimicking early-stage coeliac disease. In the current study, we sought to establish whether recombinantly produced patient-derived TG2-targeted autoantibodies are by themselves sufficient for the development of such an experimentally induced condition in immune-compromised mice. Interestingly, mice injected with coeliac patient TG2-antibodies had altered small-intestinal mucosal morphology, increased lamina propria cellular infiltration and disease-specific autoantibodies deposited in the small bowel, but did not evince clinical features of the disease. Thus, coeliac patient-derived TG2-specific autoantibodies seem to be sufficient for the induction of subtle small-bowel mucosal alterations in mice, but the development of clinical features probably requires additional factors such as other antibody populations relevant in coeliac disease.

  8. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz


    regulated by small Rho GTPases. Deletion of either Cdc42 or Rac1 in the NC results in size reduction of multiple NC target structures because of increased cell-cycle exit, while NC cells emigrating from the neural tube are not affected. Consistently, Cdc42 or Rac1 inactivation reduces self......The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially...

  9. The importance of specific human capital, planning and familiarity in Dutch small firm ownership transfers : a seller’s perspective

    NARCIS (Netherlands)

    Teeffelen, Lex van; Uhlaner, Lorraine; Driessen, Martijn


    This study focuses on the transfer process and the importance of human capital and succession planning as firm resource from the seller’s perspective. It further differentiates amongst two types of human capital - specific and generic - to predict the transfer duration, obtained price and satisf

  10. Specific IgG Antibodies React to Mimotopes of BK Polyomavirus, a Small DNA Tumor Virus, in Healthy Adult Sera (United States)

    Pietrobon, Silvia; Bononi, Ilaria; Mazzoni, Elisa; Lotito, Francesca; Manfrini, Marco; Puozzo, Andrea; Destro, Federica; Guerra, Giovanni; Nocini, Pier Francesco; Martini, Fernanda; Tognon, Mauro G.


    BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods. Serum antibodies against this polyomavirus were revealed using immunological techniques, which, however, cross-react with other polyomaviruses such as JC (JCPyV) and Simian Virus 40. These non-specific data indicate the need of novel immunological methods and new investigations to check in a specific manner, BKPyV spread in humans. To this aim, mimotopes from BKPyV structural capsid protein 1 (VP1) were employed for specific immunological reactions to IgG antibodies of human serum samples. An indirect enzyme-linked immunosorbent assay with synthetic peptides mimicking immunogenic epitopes of BKPyV VP1 was set up and employed to test sera of healthy adult subjects. Data from this innovative immunological assay indicate that serum antibodies against BKPyV VP1 mimotopes are detectable in healthy subjects ranging from 18 to 90 years old. The overall prevalence of serum samples that reacted to BKPyV VP1 mimotopes was 72%. The strong points from this investigation are the novelty of the immunological method, its simplicity of the approach, and the specificity of BKPyV antibody reaction to VP1 mimotopes. PMID:28321224

  11. Cell Type-Specific Activation of AKT and ERK Signaling Pathways by Small Negatively-Charged Magnetic Nanoparticles (United States)

    Rauch, Jens; Kolch, Walter; Mahmoudi, Morteza


    The interaction of nanoparticles (NPs) with living organisms has become a focus of public and scientific debate due to their potential wide applications in biomedicine, but also because of unwanted side effects. Here, we show that superparamagnetic iron oxide NPs (SPIONs) with different surface coatings can differentially affect signal transduction pathways. Using isogenic pairs of breast and colon derived cell lines we found that the stimulation of ERK and AKT signaling pathways by SPIONs is selectively dependent on the cell type and SPION type. In general, cells with Ras mutations respond better than their non-mutant counterparts. Small negatively charged SPIONs (snSPIONs) activated ERK to a similar extent as epidermal growth factor (EGF), and used the same upstream signaling components including activation of the EGF receptor. Importantly, snSPIONs stimulated the proliferation of Ras transformed breast epithelial cells as efficiently as EGF suggesting that NPs can mimic physiological growth factors.

  12. Gender-specific reduction of estrogen-sensitive small RNA, miR-30b, in subjects with schizophrenia. (United States)

    Mellios, Nikolaos; Galdzicka, Marzena; Ginns, Edward; Baker, Stephen P; Rogaev, Evgeny; Xu, Jun; Akbarian, Schahram


    Estrogen signaling pathways affect cortical function and metabolism, are thought to play a role in the pathophysiology of schizophrenia, and exert neuroprotective effects in female subjects at risk. However, the molecular signatures of estrogen signaling in normal and diseased cerebral cortex remain largely unexplored. Expression of the estrogen-sensitive small RNA, microRNA-30b (miR-30b), was studied in 30 controls and 30 matched samples from subjects diagnosed with schizophrenia from prefrontal cortex (PFC), as well as in 23 samples from parietal cortex (12 controls and 11 schizophrenia cases). The majority of case and control samples were genotyped for an estrogen receptor α (Esr1) sequence variant (rs2234693) previously associated with genetic risk, and a subset of them were subjected to further analysis to determine expression of mature and precursor forms of miR-30b (pre/pri-miR-30b). Gender-dimorphic expression was also explored in mouse frontal cortex and hippocampus. A significant interaction between gender and diagnosis was discovered for changes in mature miR-30b levels, so that miR-30b expression was significantly reduced in the cerebral cortex of female but not male subjects with schizophrenia. In addition, disease-related changes in miR-30b expression in a subset of female subjects were further modulated by Esr1 genotype. Changes after antipsychotic drug exposure remained insignificant. These preliminary findings point to the possibility that disease-related changes in the expression of small noncoding RNAs such as miR-30b in schizophrenia could be influenced by gender and potentially regulated by estrogen signaling.

  13. A small intergenic region drives exclusive tissue-specific expression of the adjacent genes in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Valle Estela M


    Full Text Available Abstract Background Transcription initiation by RNA polymerase II is unidirectional from most genes. In plants, divergent genes, defined as non-overlapping genes organized head-to-head, are highly represented in the Arabidopsis genome. Nevertheless, there is scarce evidence on functional analyses of these intergenic regions. The At5g06290 and At5g06280 loci are head-to-head oriented and encode a chloroplast-located 2-Cys peroxiredoxin B (2CPB and a protein of unknown function (PUF, respectively. The 2-Cys peroxiredoxins are proteins involved in redox processes, they are part of the plant antioxidant defence and also act as chaperons. In this study, the transcriptional activity of a small intergenic region (351 bp shared by At5g06290 and At5g06280 in Arabidopsis thaliana was characterized. Results Activity of the intergenic region in both orientations was analyzed by driving the β-glucuronidase (GUS reporter gene during the development and growth of Arabidopsis plants under physiological and stressful conditions. Results have shown that this region drives expression either of 2cpb or puf in photosynthetic or vascular tissues, respectively. GUS expression driven by the promoter in 2cpb orientation was enhanced by heat stress. On the other hand, the promoter in both orientations has shown similar down-regulation of GUS expression under low temperatures and other stress conditions such as mannitol, oxidative stress, or fungal elicitor. Conclusion The results from this study account for the first evidence of an intergenic region that, in opposite orientation, directs GUS expression in different spatially-localized Arabidopsis tissues in a mutually exclusive manner. Additionally, this is the first demonstration of a small intergenic region that drives expression of a gene whose product is involved in the chloroplast antioxidant defence such as 2cpb. Furthermore, these results contribute to show that 2cpb is related to the heat stress defensive system

  14. Characterization of a novel small molecule subtype specific estrogen-related receptor alpha antagonist in MCF-7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Michael J Chisamore

    Full Text Available BACKGROUND: The orphan nuclear receptor estrogen-related receptor alpha (ERRalpha is a member of the nuclear receptor superfamily. It was identified through a search for genes encoding proteins related to estrogen receptor alpha (ERalpha. An endogenous ligand has not been found. Novel ERRalpha antagonists that are highly specific for binding to the ligand binding domain (LBD of ERRalpha have been recently reported. Research suggests that ERRalpha may be a novel drug target to treat breast cancer and/or metabolic disorders and this has led to an effort to characterize the mechanisms of action of N-[(2Z-3-(4,5-dihydro-1,3-thiazol-2-yl-1,3-thiazolidin-2-yl idene]-5H dibenzo[a,d][7]annulen-5-amine, a novel ERRalpha specific antagonist. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate this ERRalpha ligand inhibits ERRalpha transcriptional activity in MCF-7 cells by luciferase assay but does not affect mRNA levels measured by real-time RT-PCR. Also, ERalpha (ESR1 mRNA levels were not affected upon treatment with the ERRalpha antagonist, but other ERRalpha (ESRRA target genes such as pS2 (TFF1, osteopontin (SPP1, and aromatase (CYP19A1 mRNA levels decreased. In vitro, the ERRalpha antagonist prevents the constitutive interaction between ERRalpha and nuclear receptor coactivators. Furthermore, we use Western blots to demonstrate ERRalpha protein degradation via the ubiquitin proteasome pathway is increased by the ERRalpha-subtype specific antagonist. We demonstrate by chromatin immunoprecipitation (ChIP that the interaction between ACADM, ESRRA, and TFF1 endogenous gene promoters and ERRalpha protein is decreased when cells are treated with the ligand. Knocking-down ERRalpha (shRNA led to similar genomic effects seen when MCF-7 cells were treated with our ERRalpha antagonist. CONCLUSIONS/SIGNIFICANCE: We report the mechanism of action of a novel ERRalpha specific antagonist that inhibits transcriptional activity of ERRalpha, disrupts the constitutive

  15. Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease ▿ (United States)

    Geelhaar, Anika; Moos, Verena; Schinnerling, Katina; Allers, Kristina; Loddenkemper, Christoph; Fenollar, Florence; LaScola, Bernard; Raoult, Didier; Schneider, Thomas


    Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection. PMID:20696822

  16. Site-specific tagging proteins with a rigid, small and stable transition metal chelator, 8-hydroxyquinoline, for paramagnetic NMR analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yin; Huang, Feng [Nankai University, State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) (China); Huber, Thomas [Australian National University, Research School of Chemistry (Australia); Su, Xun-Cheng, E-mail: [Nankai University, State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) (China)


    Design of a paramagnetic metal binding motif in a protein is a valuable way for understanding the function, dynamics and interactions of a protein by paramagnetic NMR spectroscopy. Several strategies have been proposed to site-specifically tag proteins with paramagnetic lanthanide ions. Here we report a simple approach of engineering a transition metal binding motif via site-specific labelling of a protein with 2-vinyl-8-hydroxyquinoline (2V-8HQ). The protein-2V-8HQ adduct forms a stable complex with transition metal ions, Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). The paramagnetic effects generated by these transition metal ions were evaluated by NMR spectroscopy. We show that 2V-8HQ is a rigid and stable transition metal binding tag. The coordination of the metal ion can be assisted by protein sidechains. More importantly, tunable paramagnetic tensors are simply obtained in an α-helix that possesses solvent exposed residues in positions i and i + 3, where i is the residue to be mutated to cysteine, i + 3 is Gln or Glu or i − 4 is His. The coordination of a sidechain carboxylate/amide or imidazole to cobalt(II) results in different structural geometries, leading to different paramagnetic tensors as shown by experimental data.

  17. Phage display selection on whole cells yields a small peptide specific for HCV receptor human CD81

    Institute of Scientific and Technical Information of China (English)



    The human CD81(hCD81),the most recently proposed receptor of hepatitis C virus(HCV),can especifically bind to HCV envelope glycoprotein 2(E2).In this study,hCD81-expressing murine NIH/3T3 cells were used to select hCD81-binding peptides from a phage displayed nonapeptide library(PVIII9aaCys).Eighteen of the 75clones selected from the library showed specific binding to the hCD81-expressing NIH/3T3 cells by enzyme linked immunosorbent assay(ELISA)and competitive inhibition test.Twelve out of the 18 clones shared the amino acid motif SPQYWTGPA.Sequence comparison of the motif showed no amino acid homology with the native HCV E2.The motif-containing phages could competitively inhibit the ability of HCV E2 binding to native hCD81-expressing MOLT-4 cells,and induce HCV E2 specific immune response in vivo.These results suggest that the selected motif SPQYWTGPA should be a mimotope of HCV E2 to bind to hCD81 molecules.Our findings cast new light on developing HCV receptor antagonists.

  18. Specific small-molecule activator of Aurora kinase A induces autophosphorylation in a cell-free system. (United States)

    Kishore, A Hari; Vedamurthy, B M; Mantelingu, K; Agrawal, Shipra; Reddy, B A Ashok; Roy, Siddhartha; Rangappa, K S; Kundu, Tapas K


    Aurora kinases are essential for chromosomal segregation and cell division and thereby important for maintaining the proper genomic integrity. There are three classes of aurora kinases in humans: A, B, and C. Aurora kinase A is frequently overexpressed in various cancers. The link of the overexpression and tumorigenesis is yet to be understood. By employing virtual screening, we have found that anacardic acid, a pentadecane aliphatic chain containing hydroxylcarboxylic acid, from cashew nut shell liquid could be docked in Aurora kinases A and B. Remarkably, we found that anacardic acid could potently activate the Aurora kinase A mediated phosphorylation of histone H3, but at a similar concentration the activity of aurora kinase B remained unaffected in vitro. Mechanistically, anacardic acid induces the structural changes and also the autophosphorylation of the aurora kinase A to enhance the enzyme activity. This data thus indicate anacardic acid as the first small-molecule activator of Aurora kinase, which could be highly useful for probing the function of hyperactive (overexpressed) Aurora kinase A.

  19. Rapid enzyme-linked immunosorbent assay for the detection of hantavirus-specific antibodies in divergent small mammals. (United States)

    Cautivo, Karla; Schountz, Tony; Acuña-Retamar, Mariana; Ferrés, Marcela; Torres-Pérez, Fernando


    We assessed the utility of an enzyme-linked immunosorbent assay (ELISA) for the detection of hantavirus-specific antibodies from sera of Oligoryzomys longicaudatus, the principal reservoir of Andes virus (ANDV), using an antigen previously developed for detection of antibodies to Sin Nombre virus (SNV) in sera from Peromyscus maniculatus. The assay uses a protein A/G horseradish peroxidase conjugate and can be performed in as little as 1.5 hours. Serum samples from Oligoryzomys longicaudatus collected in central-south Chile were used and the assay identified several that were antibody positive. This assay can be used for the rapid detection of antibodies to divergent hantaviruses from geographically and phylogenetically distant rodent species.

  20. Rapid Enzyme-Linked Immunosorbent Assay for the Detection of Hantavirus-Specific Antibodies in Divergent Small Mammals

    Directory of Open Access Journals (Sweden)

    Karla Cautivo


    Full Text Available We assessed the utility of an enzyme-linked immunosorbent assay (ELISA for the detection of hantavirus-specific antibodies from sera of Oligoryzomys longicaudatus, the principal reservoir of Andes virus (ANDV, using an antigen previously developed for detection of antibodies to Sin Nombre virus (SNV in sera from Peromyscus maniculatus. The assay uses a protein A/G horseradish peroxidase conjugate and can be performed in as little as 1.5 hours. Serum samples from Oligoryzomys longicaudatus collected in central-south Chile were used and the assay identified several that were antibody positive. This assay can be used for the rapid detection of antibodies to divergent hantaviruses from geographically and phylogenetically distant rodent species.

  1. First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Gupta N


    Full Text Available Neha Gupta, Hassan Hatoum, Grace K DyDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USAAbstract: Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007 is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel. A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.Keywords: ABI-007, Abraxane, nab

  2. Projections of specific morphological types of neurons within the myenteric plexus of the small intestine of the guinea-pig. (United States)

    Song, Z M; Brookes, S J; Costa, M


    The projections of myenteric neurons within the myenteric plexus of the guinea-pig small intestine were established using retrograde tracing in organotypic culture. Three days after applying the fluorescent dye DiI to a single internodal strand in the myenteric plexus, 500-1000 nerve cell bodies were labelled. Of these, 77% were located oral to the application site, 15% were located anally and 7% were located within 1 mm of this site. Three major morphological types of neurons could be distinguished. Dogiel type I neurons had lamellar dendrites and single axons, Dogiel type II neurons had large smooth cell bodies and several long processes, and filamentous neurons had smooth ovoid cell bodies, single axons and several filamentous dendrites. Dogiel type I, II and filamentous neurons accounted for 54.6%, 38% and 7.4% of all filled cells, respectively. Labelled nerve cell bodies were present up to 13 mm aboral to the DiI application site; all neurons more than 2 mm aboral had Dogiel type I features. On the oral side, Dogiel type I neurons were found up to 110 mm, Dogiel type II neurons up to 100 mm and filamentous neurons up to 80 mm. Neurons with 2 mm oral or aboral to the DiI application site were located up to 7 mm circumferentially and were mainly Dogiel type II cells. This work revealed remarkable polarity within the myenteric plexus, with a significant prevalence of myenteric neurons projecting anally for longer distances than those projecting orally. These long pathways are probably involved in the coordination of intestinal motility.

  3. A field-based method to derive macroinvertebrate benchmark for specific conductivity adapted for small data sets and demonstrated in the Hun-Tai River Basin, Northeast China. (United States)

    Zhao, Qian; Jia, Xiaobo; Xia, Rui; Lin, Jianing; Zhang, Yuan


    Ionic mixtures, measured as specific conductivity, have been increasingly concerned because of their toxicities to aquatic organisms. However, identifying protective values of specific conductivity for aquatic organisms is challenging given that laboratory test systems cannot examine more salt-intolerant species nor effects occurring in streams. Large data sets used for deriving field-based benchmarks are rarely available. In this study, a field-based method for small data sets was used to derive specific conductivity benchmark, which is expected to prevent the extirpation of 95% of local taxa from circum-neutral to alkaline waters dominated by a mixture of SO4(2-) and HCO3(-) anions and other dissolved ions. To compensate for the smaller sample size, species level analyses were combined with genus level analyses. The benchmark is based on extirpation concentration (XC95) values of specific conductivity for 60 macroinvertebrate genera estimated from 296 sampling sites in the Hun-Tai River Basin. We derived the specific conductivity benchmark by using a 2-point interpolation method, which yielded the benchmark of 249 μS/cm. Our study tailored the method that was developed by USEPA to derive aquatic life benchmark for specific conductivity for basin scale application, and may provide useful information for water pollution control and management.

  4. GeneRegionScan: a Bioconductor package for probe-level analysis of specific, small regions of the genome. (United States)

    Folkersen, Lasse; Diez, Diego; Wheelock, Craig E; Haeggström, Jesper Z; Goto, Susumu; Eriksson, Per; Gabrielsen, Anders


    Whole-genome microarrays allow us to interrogate the entire transcriptome of a cell. Affymetrix microarrays are constructed using several probes that match to different regions of a gene and a summarization step reduces this complexity into a single value, representing the expression level of the gene or the expression level of an exon in the case of exon arrays. However, this simplification eliminates information that might be useful when focusing on specific genes of interest. To address these limitations, we present a software package for the R platform that allows detailed analysis of expression at the probe level. The package matches the probe sequences against a target gene sequence (either mRNA or DNA) and shows the expression levels of each probe along the gene. It also features functions to fit a linear regression based on several genetic models that enables study of the relationship between gene expression and genotype. The software is implemented as a platform-independent R package available through the Bioconductor repository at It is licensed as GPL 2.0. Supplementary data are available at Bioinformatics online.

  5. Site-Specific Photolabeling of the IgG Fab Fragment Using a Small Protein G Derived Domain. (United States)

    Kanje, Sara; von Witting, Emma; Chiang, Samuel C C; Bryceson, Yenan T; Hober, Sophia


    Antibodies are widely used reagents for recognition in both clinic and research laboratories all over the world. For many applications, antibodies are labeled through conjugation to different reporter molecules or therapeutic agents. Traditionally, antibodies are covalently conjugated to reporter molecules via primary amines on lysines or thiols on cysteines. While efficient, such labeling is variable and nonstoichiometric and may affect an antibody's binding to its target. Moreover, an emerging field for therapeutics is antibody-drug conjugates, where a toxin or drug is conjugated to an antibody in order to increase or incorporate a therapeutic effect. It has been shown that homogeneity and controlled conjugation are crucial in these therapeutic applications. Here we present two novel protein domains developed from an IgG-binding domain of Streptococcal Protein G. These domains show obligate Fab binding and can be used for site-specific and covalent attachment exclusively to the constant part of the Fab fragment of an antibody. The two different domains can covalently label IgG of mouse and human descent. The labeled antibodies were shown to be functional in both an ELISA and in an NK-cell antibody-dependent cellular cytotoxicity assay. These engineered protein domains provide novel tools for controlled labeling of Fab fragments and full-length IgG.

  6. Raman and surface enhanced Raman spectroscopic studies of specific, small molecule activator of histone acetyltransferase p300 (United States)

    Kundu, Partha P.; Pavan Kumar, G. V.; Mantelingu, Kempegowda; Kundu, Tapas K.; Narayana, Chandrabhas


    We report for the first time, the Raman and surface enhanced Raman scattering (SERS) studies of N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide (CTB). This molecule is specific activator of human histone acetyltransferase (HAT), p300, and serves as lead molecule to design anti-neoplastic therapeutics. A detailed Raman and SERS band assignments have been performed for CTB, which are compared with the density functional theory calculations. The observed red shift of N sbnd H stretching frequency from the computed wavenumber indicates the weakening of N sbnd H bond resulting from proton transfer to the neighboring oxygen atom. We observe Ag sbnd N vibrational mode at 234 cm -1 in SERS of CTB. This indicates there is a metal-molecule bond leading to chemical enhancement in SERS. We also observe, enhancement in the modes pertaining to substituted benzene rings and methyl groups. Based on SERS analysis we propose the adsorption sites and the orientation of CTB on silver surface.

  7. The Fleas of Endemic and Introduced Small Mammals in Central Highland Forests of Madagascar: Faunistics, Species Diversity, and Absence of Host Specificity. (United States)

    Goodman, Steven M; Randrenjarison Andriniaina, H Rico; Soarimalala, Voahangy; Beaucournu, Jean-Claude


    Data are presented on the flea species of the genera Paractenopsyllus (Ceratophyllidae, Leptopsyllinae) and Synopsyllus (Pulicidae, Xenopsyllinae) obtained from small mammals during two 2014 seasonal surveys at a montane humid forest site (Ambohitantely) in the Central Highlands of Madagascar. The mammal groups included the endemic family Tenrecidae (tenrecs) and subfamily Nesomyinae (rodents) and two introduced families Muridae (rodents) and Soricidae (shrews); no fleas were recovered from the latter family. The surveys were conducted at the end of the wet and dry seasons with 288 individual small mammals captured, including 12 endemic and four introduced species. These animals yielded 344 fleas, representing nine species endemic to Madagascar; no introduced species was collected. Some seasonal variation was found in the number of trapped small mammals, but no marked difference was found in species richness. For flea species represented by sufficient samples, no parasite-host specificity was found, and there is evidence for considerable lateral exchange in the local flea fauna between species of tenrecs and the two rodent families (endemic and introduced). The implications of these results are discussed with regards to small mammal species richness and community structure, as well as a possible mechanism for the maintenance of sylvatic cycles of bubonic plague in the montane forests of Madagascar.

  8. [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency. (United States)

    Jensen, Jonas B; Sundelin, Elias I; Jakobsen, Steen; Gormsen, Lars C; Munk, Ole L; Frøkiær, Jørgen; Jessen, Niels


    Metformin is the most commonly prescribed oral antidiabetic drug, with well-documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies.

  9. Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol. (United States)

    Duin, Evert C; Wagner, Tristan; Shima, Seigo; Prakash, Divya; Cronin, Bryan; Yáñez-Ruiz, David R; Duval, Stephane; Rümbeli, Robert; Stemmler, René T; Thauer, Rudolf Kurt; Kindermann, Maik


    Ruminants, such as cows, sheep, and goats, predominantly ferment in their rumen plant material to acetate, propionate, butyrate, CO2, and methane. Whereas the short fatty acids are absorbed and metabolized by the animals, the greenhouse gas methane escapes via eructation and breathing of the animals into the atmosphere. Along with the methane, up to 12% of the gross energy content of the feedstock is lost. Therefore, our recent report has raised interest in 3-nitrooxypropanol (3-NOP), which when added to the feed of ruminants in milligram amounts persistently reduces enteric methane emissions from livestock without apparent negative side effects [Hristov AN, et al. (2015) Proc Natl Acad Sci USA 112(34):10663-10668]. We now show with the aid of in silico, in vitro, and in vivo experiments that 3-NOP specifically targets methyl-coenzyme M reductase (MCR). The nickel enzyme, which is only active when its Ni ion is in the +1 oxidation state, catalyzes the methane-forming step in the rumen fermentation. Molecular docking suggested that 3-NOP preferably binds into the active site of MCR in a pose that places its reducible nitrate group in electron transfer distance to Ni(I). With purified MCR, we found that 3-NOP indeed inactivates MCR at micromolar concentrations by oxidation of its active site Ni(I). Concomitantly, the nitrate ester is reduced to nitrite, which also inactivates MCR at micromolar concentrations by oxidation of Ni(I). Using pure cultures, 3-NOP is demonstrated to inhibit growth of methanogenic archaea at concentrations that do not affect the growth of nonmethanogenic bacteria in the rumen.

  10. The tRNA-Derived Small RNAs Regulate Gene Expression through Triggering Sequence-Specific Degradation of Target Transcripts in the Oomycete Pathogen Phytophthora sojae (United States)

    Wang, Qinhu; Li, Tingting; Xu, Ke; Zhang, Wei; Wang, Xiaolong; Quan, Junli; Jin, Weibo; Zhang, Meixiang; Fan, Guangjin; Wang, Ming-Bo; Shan, Weixing


    Along with the well-studied microRNA (miRNA) and small interfering RNA (siRNA) is a new class of transfer RNA-derived small RNA (tsRNA), which has recently been detected in multiple organisms and is implicated in gene regulation. However, while miRNAs and siRNAs are known to repress gene expression through sequence-specific RNA cleavage or translational repression, how tsRNAs regulate gene expression remains unclear. Here we report the identification and functional characterization of tsRNAs in the oomycete pathogen Phytophthora sojae. We show that multiple tRNAs are processed into abundant tsRNAs, which accumulate in a similar developmental stage-specific manner and are negatively correlated with the expression of predicted target genes. Degradome sequencing and 5′ RLM RACE experiments indicate tsRNAs can trigger degradation of target transcripts. Transient expression assays using GUS sensor constructs confirmed the requirement of sequence complementarity in tsRNA-mediated RNA degradation in P. sojae. Our results show that the tsRNA are a class of functional endogenous sRNAs and suggest that tsRNA regulate gene expression through inducing sequence-specific degradation of target RNAs in oomycetes. PMID:28066490

  11. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen


    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  12. Improved specificity of {sup 18}F-FDG PET/CT for lymph node staging of non-small cell lung cancer considering calcified lymph node as benign

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Seong Young; Seo, Young Soon; Min, Jung Joon; Song, Ho Chun; Na, Kook Joo; Choi, Chan; Kim, Young Chul; Kim, Yun Hyun; Bom, Hee Seung [Chonnam National University Hospital, Gwangju (Korea, Republic of)


    We evaluated the diagnostic value of {sup 18}F-FDG PET/CT (PET/CT) in lymph node staging of non-small cell lung cancer (NSCLC) considering calcification and histologic types as well as FDG uptake. Fifty-three patients (38 men, 15 women; mean age, 62 years) with NSCLC underwent surgical resection (tumor resection and lymph node dissection) after PET/CT. After surgery, we compared PET/CT results with the biopsy results, and analyzed lymph node metastases, based on histologic types. PET diagnosis of lymph node metastasis was determined by maximum SUV (maxSUV) > 3.0, and PET/CT diagnosis was determined by maxSUV > 3.0 without lymph node calcification. By PET diagnosis, the sensitivity, specificity, and accuracy of overall lymph node staging were 45% (13 of 29), 91% (228 of 252), and 86% (241 of 281). Specificity was 91% in both squamous cell carcinoma and adenocarcinoma, while sensitivity was 71% in squamous cell carcinoma and 36% in adenocarcinoma. When we excluded calcified lymph node with maxSUV > 3.0 from metastasis by PET/CT diagnosis, specificity improved to 98% in squamous cell carcinoma and 97% in adenocarcinoma. The degree of improvement was not dependent on histologic types. PET/CT improved specificity of lymph node staging by reducing false positive lymph node regardless of histologic types of NSCLC.

  13. Chemotherapeutic drugs induce PPAR-gamma expression and show sequence-specific synergy with PPAR-gamma ligands in inhibition of non-small cell lung cancer. (United States)

    Reddy, Raju C; Srirangam, Anjaiah; Reddy, Kaunteya; Chen, Jun; Gangireddy, Srinivasareddy; Kalemkerian, Gregory P; Standiford, Theodore J; Keshamouni, Venkateshwar G


    Preclinical studies have shown that peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligands can exert antitumor effects against non-small cell lung cancer (NSCLC) and a variety of other cancers. In this study, we investigate the potential use of a PPAR-gamma ligand, troglitazone (Tro), in combination with either of two chemotherapeutic agents, cisplatin (Cis) or paclitaxel (Pac), for the treatment of NSCLC. In vitro, treatment of NSCLC cell lines with Tro potentiated Cis- or Pac-induced growth inhibition. The potentiation of growth inhibition was observed only when Cis or Pac treatment was followed by Tro and not vice versa, demonstrating a sequence-specific effect. Median effect analysis revealed a synergistic interaction between Tro and Cis in the inhibition of NSCLC cell growth and confirmed the sequence-specific effect. We also found that Cis or Pac up-regulated the expression of PPAR-gamma protein, accounting for the observed sequence-specific synergy. Similarly, experiments performed using a NSCLC xenograft model demonstrated enhanced effectiveness of combined treatment with Cis and PPAR-gamma ligands, Tro or pioglitazone. Tumors from Cis-treated mice also demonstrated enhanced PPAR-gamma expression. Together, our data demonstrate a novel sequence-specific synergy between PPAR-gamma ligands and chemotherapeutic agents for lung cancer treatment.

  14. Chemotherapeutic Drugs Induce PPAR-γ Expression and Show Sequence-Specific Synergy with PPAR-γ Ligands in Inhibition of Non-Small Cell Lung Cancer1 (United States)

    Reddy, Raju C; Srirangam, Anjaiah; Reddy, Kaunteya; Chen, Jun; Gangireddy, Srinivasareddy; Kalemkerian, Gregory P; Standiford, Theodore J; Keshamouni, Venkateshwar G


    Preclinical studies have shown that peroxisome proliferator-activated receptor γ (PPAR-γ) ligands can exert antitumor effects against non-small cell lung cancer (NSCLC) and a variety of other cancers. In this study, we investigate the potential use of a PPAR-γ ligand, troglitazone (Tro), in combination with either of two chemotherapeutic agents, cisplatin (Cis) or paclitaxel (Pac), for the treatment of NSCLC. In vitro, treatment of NSCLC cell lines with Tro potentiated Cis- or Pac-induced growth inhibition. The potentiation of growth inhibition was observed only when Cis or Pac treatment was followed by Tro and not vice versa, demonstrating a sequence-specific effect. Median effect analysis revealed a synergistic interaction between Tro and Cis in the inhibition of NSCLC cell growth and confirmed the sequence-specific effect. We also found that Cis or Pac up-regulated the expression of PPAR-γ protein, accounting for the observed sequence-specific synergy. Similarly, experiments performed using a NSCLC xenograft model demonstrated enhanced effectiveness of combined treatment with Cis and PPAR-γ ligands, Tro or pioglitazone. Tumors from Cis-treated mice also demonstrated enhanced PPAR-γ expression. Together, our data demonstrate a novel sequence-specific synergy between PPAR-γ ligands and chemotherapeutic agents for lung cancer treatment. PMID:18516296

  15. Molecular cloning, characterization and tissue specificity of the expression of the ovine CSRP2 and CSRP3 genes from Small-tail Han sheep (Ovis aries). (United States)

    Liu, Guanqing; Zhang, Chunlan; Wang, Guizhi; Ji, Zhibin; Liu, Zhaohua; Chao, Tianle; Zhang, Saisai; Wang, Jianmin


    Two genes, cysteine- and glycine-rich protein 2 (CSRP2) and cysteine- and glycine-rich protein 3 (CSRP3), play important roles in tissue-specific cell growth and development. However, few CSRP2 and CSRP3 genes have been functionally characterized in sheep. In this study, the full-length cDNAs of the CSRP2 and CSRP3 genes were cloned from Small-tail Han sheep by rapid amplification of cDNA ends-PCR. The GenBank accession numbers of the full-length CSRP2 and CSRP3 cDNA sequences are KJ743957 and KJ743958, respectively. The full-length cDNA of ovine CSRP2 was 917bp, with a 582-bp open reading frame encoding 193 amino acids. The complete ovine CSRP3 cDNA was 917bp, with a 585-bp open reading frame encoding 194 amino acids. Alignment and phylogenetic analyses revealed that their amino acid sequences are highly similar to those of other vertebrates, all of which contain two conserved LIM-only domains and a relatively conserved nuclear targeting sequence. To further validate the functions of the two genes, their mRNA expression patterns were evaluated in various Small-tail Han and Dorper sheep tissues using qRT-PCR analyses. CSRP2 was mainly detected in the aorta, whereas CSRP3 was highly concentrated in the heart and the muscle. CSRP3 was expressed to a higher level in the hearts of Small-tail Han sheep than in Dorper sheep (P<0.05). However, the opposite was found in the muscle (the longissimus dorsi and biceps femoris); CSRP3 was expressed to a higher level in Dorper sheep than in Small-tail Han sheep (P<0.05). We quantified the CRP3 protein (coded by the CSRP3 gene) levels in different tissues in Small-tail Han and Dorper sheep. We also detected a putative isoform of the CRP3 protein in sheep, which was significantly different in the heart tissue of the two breeds (P<0.05). The expression patterns of the two genes' mRNAs and CRP3 protein showed clear tissue specificity in both sheep breeds.

  16. High-affinity Near-infrared Fluorescent Small-molecule Contrast Agents for In Vivo Imaging of Prostate-specific Membrane Antigen

    Directory of Open Access Journals (Sweden)

    Valerie Humblet


    Full Text Available Surgical resection remains a definitive treatment for prostate cancer. Yet, prostate cancer surgery is performed without image guidance for tumor margin, extension beyond the capsule and lymph node positivity, and without verification of other occult metastases in the surgical field. Recently, several imaging systems have been described that exploit near-infrared (NIR fluorescent light for sensitive, real-time detection of disease pathology intraoperatively. In this study, we describe a high-affinity (9 nM, single nucleophile-containing, small molecule specific for the active site of the enzyme PSMA. We demonstrate production of a tetra-sulfonated heptamethine indocyanine NIR fluorescent derivative of this molecule using a high-yield LC/MS purification strategy. Interestingly, NIR fluorophore conjugation improves affinity over 20-fold, and we provide mechanistic insight into this observation. We describe the preparative production of enzymatically active PSMA using a baculovirus expression system and an adenovirus that co-expresses PSMA and GFP. We demonstrate sensitive and specific in vitro imaging of endogenous and ectopically expressed PSMA in human cells and in vivo imaging of xenograft tumors. We also discuss chemical strategies for improving performance even further. Taken together, this study describes nearly complete preclinical development of an optically based small-molecule contrast agent for image-guided surgery.

  17. Correlation of bulk sedimentary and compound-specific δ13C values indicates minimal pre-aging of n-alkanes in a small tropical watershed (United States)

    Lane, Chad S.; Horn, Sally P.; Taylor, Zachary P.; Kerr, Matthew T.


    Inherent to sedimentary compound-specific isotopic proxies of paleoecological and paleoclimate change is the assumption that biomarkers are coeval with the surrounding sedimentary matrix. Compound-specific radiocarbon analyses of lake and nearshore marine sediments have indicated a potential offset between the ages of terrestrial biomarkers and their surrounding sediments that could confound efforts to establish strong chronological control for compound-specific isotopic data. We conducted high-resolution compound-specific δ13C analyses of n-alkanes (δ13Calkane) in a well-studied sediment core from Laguna Castilla, Dominican Republic, and compared the results to bulk sedimentary δ13C (δ13Cbulk), fossil pollen, and sediment geochemistry to assess potential 'pre-aging' of alkanes in the terrestrial environment prior to deposition. We found significant positive correlations between δ13Cbulk values and δ13Calkane values, indicating little or no temporal lag in the response of δ13Calkane values to vegetation change and thus little or no offset in the age of terrestrially-derived compounds and the organic fraction of the sedimentary matrix. While this study highlights the need for further research into the variables affecting age offsets between proxy data, we propose the comparison of δ13Cbulk and δ13Calkane values as a method to assess potential age offsets between compound-specific and other proxy datasets, particularly in small watersheds with sediment records containing a high proportion of allochthonous organic matter. This method is more available to researchers than obtaining numerous compound-specific radiocarbon analyses, which are costly and not a routine service offered by radiocarbon facilities.

  18. Detector to detector corrections: A comprehensive experimental study of detector specific correction factors for beam output measurements for small radiotherapy beams

    Energy Technology Data Exchange (ETDEWEB)

    Azangwe, Godfrey, E-mail:; Grochowska, Paulina; Izewska, Joanna; Meghzifene, Ahmed [International Atomic Energy Agency, Vienna International Centre, PO Box 100, 1400 Vienna (Austria); Georg, Dietmar; Hopfgartner, Johannes; Lechner, Wolfgang [Department of Radiation Oncology, Medical University Vienna/AKH Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria and Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University Vienna, Vienna, Währinger Gürtel 18-20, A-1090 Vienna (Austria); Andersen, Claus E.; Beierholm, Anders R.; Helt-Hansen, Jakob [Center for Nuclear Technologies, Technical University of Denmark, Risø Campus, DK-4000 Roskilde (Denmark); Mizuno, Hideyuki; Fukumura, Akifumi [National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba-shi 263-8555 (Japan); Yajima, Kaori [Association for Nuclear Technology in Medicine, 7-16, Nihonbashikodenmacho, chuou-ku, Tokyo 103-0001 (Japan); Gouldstone, Clare; Sharpe, Peter [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW (United Kingdom); Palmans, Hugo [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW, United Kingdom and EBG MedAustron GmbH, Medical Physics Department, A-2700 Wiener Neustadt (Austria)


    Purpose: The aim of the present study is to provide a comprehensive set of detector specific correction factors for beam output measurements for small beams, for a wide range of real time and passive detectors. The detector specific correction factors determined in this study may be potentially useful as a reference data set for small beam dosimetry measurements. Methods: Dose response of passive and real time detectors was investigated for small field sizes shaped with a micromultileaf collimator ranging from 0.6 × 0.6 cm{sup 2} to 4.2 × 4.2 cm{sup 2} and the measurements were extended to larger fields of up to 10 × 10 cm{sup 2}. Measurements were performed at 5 cm depth, in a 6 MV photon beam. Detectors used included alanine, thermoluminescent dosimeters (TLDs), stereotactic diode, electron diode, photon diode, radiophotoluminescent dosimeters (RPLDs), radioluminescence detector based on carbon-doped aluminium oxide (Al{sub 2}O{sub 3}:C), organic plastic scintillators, diamond detectors, liquid filled ion chamber, and a range of small volume air filled ionization chambers (volumes ranging from 0.002 cm{sup 3} to 0.3 cm{sup 3}). All detector measurements were corrected for volume averaging effect and compared with dose ratios determined from alanine to derive a detector correction factors that account for beam perturbation related to nonwater equivalence of the detector materials. Results: For the detectors used in this study, volume averaging corrections ranged from unity for the smallest detectors such as the diodes, 1.148 for the 0.14 cm{sup 3} air filled ionization chamber and were as high as 1.924 for the 0.3 cm{sup 3} ionization chamber. After applying volume averaging corrections, the detector readings were consistent among themselves and with alanine measurements for several small detectors but they differed for larger detectors, in particular for some small ionization chambers with volumes larger than 0.1 cm{sup 3}. Conclusions: The results demonstrate

  19. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;


    determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy.......Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...

  20. Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: towards the next generation HIV-1 inhibitors. (United States)

    Radi, Marco; Falchi, Federico; Garbelli, Anna; Samuele, Alberta; Bernardo, Vincenzo; Paolucci, Stefania; Baldanti, Fausto; Schenone, Silvia; Manetti, Fabrizio; Maga, Giovanni; Botta, Maurizio


    Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. Here we describe the identification of the first small molecules specifically designed to inhibit the HIV-1 replication by targeting the RNA binding site of the human DEAD-Box RNA helicase DDX3. Optimization of a easily synthetically accessible hit (1) identified by application of a high-throughput docking approach afforded the promising compounds 6 and 8 which proved to inhibit both the helicase and ATPase activity of DDX3 and to reduce the viral load of peripheral blood mononuclear cells (PBMC) infected with HIV-1.

  1. Subcellular localization of the stripe disease-specific protein encoded by rice stripe virus (RSV) in its vector, the small brown planthopper, Laodelphax striatellus

    Institute of Scientific and Technical Information of China (English)


    The stripe disease-specific protein (SP) encoded by the rice stripe virus (RSV) was successfully used as a localization signal of the virus in its vector, the small brown lanthopper, Laodelphax striatellus Fallen. Immunogold parficles in large numbers were detected in various parts of the viruliferous females: the ovum, surface of chorion, the midgut lumen, and the columnar cells. Whereas there was none of these particles in the non-viruliferous females and males,and testis of viruliferous males. Endosymbionts (mycetocytes)were abundant, harboring ovaries of both viruliferous and non-viruliferous females, but none in the testis of males. The results provided us with the direct proof that RSV is a ciruculative and propagative plant virus and it was transovarially transmitted alongside with endosymbionts of its vector. Therefore, we deem it a nice lead for future studies on the mechanism of RSV transmission and functioning of its viral proteins.

  2. Detection of EGFR mutations in plasma and biopsies from non-small cell lung cancer patients by allele-specific PCR assays

    DEFF Research Database (Denmark)

    Weber, Britta; Meldgaard, Peter; Hager, Henrik


    BACKGROUND: Lung cancer patients with mutations in the epidermal growth factor receptor (EGFR) are primary candidates for EGFR-targeted therapy. Reliable analyses of such mutations have previously been possible only in tumour tissue. Here, we demonstrate that mutations can be detected in plasma...... samples with allele-specific PCR assays. METHODS: Pairs of the diagnostic biopsy and plasma obtained just prior to start of erlotinib treatment were collected from 199 patients with adenocarcinoma of non-small-cell lung cancer. DNA from both sample types was isolated and examined for the presence...... identified in 24/199 (12%) plasma samples and 28/196 (14%) biopsy samples, and 17/196 (9%) matched pairs contained the same mutation. Six EGFR mutations were present only in plasma samples but not in the biopsy samples. The overall concordance of the EGFR gene mutations detected in plasma and biopsy tissue...

  3. Stage and cell-specific expression and intracellular localization of the small heat shock protein Hsp27 during oogenesis and spermatogenesis in the Mediterranean fruit fly, Ceratitis capitata. (United States)

    Economou, Katerina; Kotsiliti, Elena; Mintzas, Anastassios C


    The cell-specific expression and intracellular distribution of the small heat protein Hsp27 was investigated in the ovaries and testes of the Mediterranean fruit fly, Ceratitis capitata (medfly), under both normal and heat shock conditions. For this study, a gfp-hsp27 strain was used to detect the chimeric protein by confocal microscopy. In unstressed ovaries, the protein was expressed throughout egg development in a stage and cell-specific pattern. In germarium, the protein was detected in the cytoplasm of the somatic cells in both unstressed and heat-shocked ovaries. In the early stages of oogenesis of unstressed ovaries, the protein was mainly located in the perinuclear region of the germ cells and in the cytoplasm of the follicle cells, while in later stages (9-10) it was distributed in the cytoplasm of the germ cells. In late stages (12-14), the protein changed localization pattern and was exclusively associated with the nuclei of the somatic cells. In heat shocked ovaries, the protein was mainly located in the nuclei of the somatic cells throughout egg chamber's development. In unstressed testes, the chimeric protein was detected in the nuclei of primary spermatocytes and in the filamentous structures of spermatid bundles, called actin cones. Interestingly, after a heat shock, the protein presented the same cell-specific localization pattern as in unstressed testes. Furthermore, the protein was also detected in the nuclei of the epithelial cells of the deferent duct, the accessory glands and the ejaculatory bulb. Our data suggest that medfly Hsp27 may have cell-specific functions, especially in the nucleus. Moreover, the association of this protein to actin cones during spermatid individualization, suggests a possible role of the protein in the formation and stabilization of actin cones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells. (United States)

    Lund, Riikka J; Rahkonen, Nelly; Malonzo, Maia; Kauko, Leni; Emani, Maheswara Reddy; Kivinen, Virpi; Närvä, Elisa; Kemppainen, Esko; Laiho, Asta; Skottman, Heli; Hovatta, Outi; Rasool, Omid; Nykter, Matti; Lähdesmäki, Harri; Lahesmaa, Riitta


    POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing analysis of polyA(+) and smallRNA transcriptomes present in hPSCs and regulated in POLR3G-dependent manner. Our data reveal that POLR3G regulates a specific subset of the hPSC transcriptome, including multiple transcript types, such as protein-coding genes, long intervening non-coding RNAs, microRNAs and small nucleolar RNAs, and affects RNA splicing. The primary function of POLR3G is in the maintenance rather than repression of transcription. The majority of POLR3G polyA(+) transcriptome is regulated during differentiation, and the key pluripotency factors bind to the promoters of at least 30% of the POLR3G-regulated transcripts. Among the direct targets of POLR3G, POLG is potentially important in sustaining stem cell status in a POLR3G-dependent manner. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type. (United States)

    Conlon, Niamh; Silva, Annacarolina; Guerra, Esther; Jelinic, Petar; Schlappe, Brooke A; Olvera, Narciso; Mueller, Jennifer J; Tornos, Carmen; Jungbluth, Achim A; Young, Robert H; Oliva, Esther; Levine, Douglas; Soslow, Robert A


    Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare ovarian neoplasm that occurs in young women and has a poor prognosis. The histologic diagnosis of SCCOHT can be challenging due to its rarity and relatively nonspecific histologic features, which range from the classic, first-described small cell morphology to a pattern in which there are large cells with abundant eosinophilic cytoplasm. Many entities can be in the differential diagnosis and to date, immunohistochemical stains have shown no distinctive profile and have been of limited aid. SMARCA4 (also known as BRG1) mutations have recently been reported at high frequency in these tumors. SMARCA4 is an important component of the SWI/SNF complex that regulates gene expression through alteration of nucleosome conformation. Studies to date have suggested that immunohistochemical loss of expression of SMARCA4 is associated with the presence of a SMARCA4 mutation in most cases. In this study, the sensitivity and specificity of the immunohistochemical loss of SMARCA4 expression for the diagnosis of SCCOHT is examined in the context of the differential diagnosis with other primary or metastatic ovarian tumors. All but one of the SCCOHT showed loss of SMARCA4 expression (16/17; 94%), while of 279 other tumors tested, only two tumors (one clear cell carcinoma and one ovarian melanoma) showed loss of SMARCA4 expression. We conclude that SMARCA4 immunohistochemistry is highly sensitive and specific for a diagnosis of SCCOHT and is of clinical utility in the differential diagnosis of poorly differentiated ovarian tumors.

  6. Small intestinal mucosa IgE plasma cells and specific anti-cow milk IgE in children with cow milk protein intolerance. (United States)

    Schrander, J J; Dellevoet, J J; Arends, J W; Forget, P P; Kuijten, R


    In a prospective study we looked for the presence of both IgE plasma cells in small bowel mucosa and specific serum IgE antibodies to cow milk in children suspected of cow milk protein intolerance. Thirty-one children with complaints possibly due to cow milk intolerance were submitted to two consecutive cow milk elimination/challenge tests. The diagnosis of cow milk protein intolerance was confirmed in 16 of our 31 patients on the basis of two positive elimination/challenge tests. IgE plasma cells were found in nine of 16 patients with proven cow milk protein intolerance and in only one of the 15 patients without cow milk protein intolerance (p < .01). The RAST for cow milk was positive in six of 16 infants with cow milk protein intolerance and in two of the 15 other infants. Serum IgE level was of no value for the diagnosis of cow milk protein intolerance. Neither of these diagnostic procedures was sensitive enough to be used as a screening test for cow milk protein intolerance. Furthermore, the relationship between specific IgE antibodies for cow milk and the presence of mucosal IgE plasma cells was poor: five of nine infants with cow milk protein intolerance and the presence of mucosal IgE plasma cells had negative RASTs for cow milk.

  7. A Small Indel Mutant Mouse Model of Epidermolytic Palmoplantar Keratoderma and Its Application to Mutant-specific shRNA Therapy. (United States)

    Lyu, Ya-Su; Shi, Pei-Liang; Chen, Xiao-Ling; Tang, Yue-Xiao; Wang, Yan-Fang; Liu, Rong-Rong; Luan, Xiao-Rui; Fang, Yu; Mei, Ru-Huan; Du, Zhen-Fang; Ke, Hai-Ping; Matro, Erik; Li, Ling-En; Lin, Zhao-Yu; Zhao, Jing; Gao, Xiang; Zhang, Xian-Ning


    Epidermolytic palmoplantar keratoderma (EPPK) is a relatively common autosomal-dominant skin disorder caused by mutations in the keratin 9 gene (KRT9), with few therapeutic options for the affected so far. Here, we report a knock-in transgenic mouse model that carried a small insertion-deletion (indel) mutant of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), corresponding to the human mutation KRT9/c.500delAinsGGCT (p.Tyr167delinsTrpLeu), which resulted in a human EPPK-like phenotype in the weight-stress areas of the fore- and hind-paws of both Krt9(+/mut) and Krt9(mut/mut) mice. The phenotype confirmed that EPPK is a dominant-negative condition, such that mice heterozygotic for the K9-mutant allele (Krt9(+/mut)) showed a clear EPPK-like phenotype. Then, we developed a mutant-specific short hairpin RNA (shRNA) therapy for EPPK mice. Mutant-specific shRNAs were systematically identified in vitro using a luciferase reporter gene assay and delivered into Krt9(+/mut) mice. shRNA-mediated knockdown of mutant protein resulted in almost normal morphology and functions of the skin, whereas the same shRNA had a negligible effect in wild-type K9 mice. Our results suggest that EPPK can be treated by gene therapy, and this has significant implications for future clinical application.

  8. Quantum dots immunofluorescence histochemical detection of EGFR gene mutations in the non-small cell lung cancers using mutation-specific antibodies

    Directory of Open Access Journals (Sweden)

    Qu YG


    Full Text Available Yan-Gang Qu,1 Qian Zhang,2 Qi Pan,3 Xian-Da Zhao,4 Yan-Hua Huang,2 Fu-Chun Chen,3 Hong-Lei Chen41Department of Pathology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, 2Department of Molecular Pathology, Wuhan Nano Tumor Diagnosis Engineering Research Center, Wuhan, Hubei, People’s Republic of China; 3Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, People’s Republic of China; 4Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei, People’s Republic of ChinaBackground: Epidermal growth factor receptor (EGFR mutation status plays an important role in therapeutic decision making for non-small cell lung cancer (NSCLC patients. Since EGFR mutation-specific antibodies (E746-A750del and L858R have been developed, EGFR mutation detection by immunohistochemistry (IHC is a suitable screening test. On this basis, we want to establish a new screening test, quantum dots immunofluorescence histochemistry (QDs-IHC, to assess EGFR gene mutation in NSCLC tissues, and we compared it to traditional IHC and amplification refractory mutation system (ARMS.Materials and methods: EGFR gene mutations were detected by QDs-IHC, IHC, and ADx-ARMS in 65 cases of NSCLC composed of 55 formalin-fixed, paraffin-embedded specimens and ten pleural effusion cell blocks, including 13 squamous cell carcinomas, two adenosquamous carcinomas, and 50 adenocarcinomas.Results: Positive rates of EGFR gene mutations detected by QDs-IHC, IHC, and ADx-ARMS were 40.0%, 36.9%, and 46.2%, respectively, in 65 cases of NSCLC patients. The sensitivity of QDs-IHC when detecting EGFR mutations, as compared to ADx-ARMS, was 86.7% (26/30; the specificity for both antibodies was 100.0% (26/26. IHC sensitivity was 80.0% (24/30 and the specificity was 92.31% (24/26. When detecting EGFR mutations, QDs-IHC and ADx-ARMS had perfect consistency (κ=0.882; P<0.01. Excellent agreement was observed

  9. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)


    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were

  10. Comparative study of the binding pockets of mammalian proprotein convertases and its implications for the design of specific small molecule inhibitors

    Directory of Open Access Journals (Sweden)

    Sun Tian, Wu Jianhua


    Full Text Available Proprotein convertases are enzymes that proteolytically cleave protein precursors in the secretory pathway to yield functional proteins. Seven mammalian subtilisin/Kex2p-like proprotein convertases have been identified: furin, PC1, PC2, PC4, PACE4, PC5 and PC7. The binding pockets of all seven proprotein convertases are evolutionarily conserved and highly similar. Among the seven proprotein convertases, the furin cleavage site motif has recently been characterized as a 20-residue motif that includes one core region P6-P2´ inside the furin binding pocket. This study extended this information by examining the 3D structural environment of the furin binding pocket surrounding the core region P6-P2´ of furin substrates. The physical properties of mutations in the binding pockets of the other six mammalian proprotein convertases were compared. The results suggest that: 1 mutations at two positions, Glu230 and Glu257, change the overall density of the negative charge of the binding pockets, and govern the substrate specificities of mammalian proprotein convertases; 2 two proprotein convertases (PC1 and PC2 may have reduced sensitivity for positively charged residues at substrate position P5 or P6, whereas the substrate specificities of three proprotein convertases (furin, PACE4, and PC5 are similar to each other. This finding led to a novel design of a short peptide pattern for small molecule inhibitors: [K/R]-X-V-X-K-R. Compared with the widely used small molecule dec-RVKR-cmk that inhibits all seven proprotein convertases, a finely-tuned derivative of the short peptide pattern [K/R]-X-V-X-K-R may have the potential to more effectively inhibit five of the proprotein convertases (furin, PC4, PACE4, PC5 and PC7 compared to the remaining two (PC1 and PC2. The results not only provide insights into the molecular evolution of enzyme function in the proprotein convertase family, but will also aid the study of the functional redundancy of proprotein

  11. DNA immunization combined with scFv phage display identifies antagonistic GCGR specific antibodies and reveals new epitopes on the small extracellular loops. (United States)

    van der Woning, Bas; De Boeck, Gitte; Blanchetot, Christophe; Bobkov, Vladimir; Klarenbeek, Alex; Saunders, Michael; Waelbroeck, Magali; Laeremans, Toon; Steyaert, Jan; Hultberg, Anna; De Haard, Hans


    The identification of functional monoclonal antibodies directed against G-protein coupled receptors (GPCRs) is challenging because of the membrane-embedded topology of these molecules. Here, we report the successful combination of llama DNA immunization with scFv-phage display and selections using virus-like particles (VLP) and the recombinant extracellular domain of the GPCR glucagon receptor (GCGR), resulting in glucagon receptor-specific antagonistic antibodies. By immunizing outbred llamas with plasmid DNA containing the human GCGR gene, we sought to provoke their immune system, which generated a high IgG1 response. Phage selections on VLPs allowed the identification of mAbs against the extracellular loop regions (ECL) of GCGR, in addition to multiple VH families interacting with the extracellular domain (ECD) of GCGR. Identifying mAbs binding to the ECL regions of GCGR is challenging because the large ECD covers the small ECLs in the energetically most favorable 'closed conformation' of GCGR. Comparison of Fab with scFv-phage display demonstrated that the multivalent nature of scFv display is essential for the identification of GCGR specific clones by selections on VLPs because of avid interaction. Ten different VH families that bound 5 different epitopes on the ECD of GCGR were derived from only 2 DNA-immunized llamas. Seven VH families demonstrated interference with glucagon-mediated cAMP increase. This combination of technologies proved applicable in identifying multiple functional binders in the class B GPCR context, suggesting it is a robust approach for tackling difficult membrane proteins.

  12. Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures. (United States)

    Du, Zhimei; Treiber, David; McCarter, John D; Fomina-Yadlin, Dina; Saleem, Ramsey A; McCoy, Rebecca E; Zhang, Yuling; Tharmalingam, Tharmala; Leith, Matthew; Follstad, Brian D; Dell, Brad; Grisim, Brent; Zupke, Craig; Heath, Carole; Morris, Arvia E; Reddy, Pranhitha


    The continued need to improve therapeutic recombinant protein productivity has led to ongoing assessment of appropriate strategies in the biopharmaceutical industry to establish robust processes with optimized critical variables, that is, viable cell density (VCD) and specific productivity (product per cell, qP). Even though high VCD is a positive factor for titer, uncontrolled proliferation beyond a certain cell mass is also undesirable. To enable efficient process development to achieve consistent and predictable growth arrest while maintaining VCD, as well as improving qP, without negative impacts on product quality from clone to clone, we identified an approach that directly targets the cell cycle G1-checkpoint by selectively inhibiting the function of cyclin dependent kinases (CDK) 4/6 with a small molecule compound. Results from studies on multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrate that the selective inhibitor can mediate a complete and sustained G0/G1 arrest without impacting G2/M phase. Cell proliferation is consistently and rapidly controlled in all recombinant cell lines at one concentration of this inhibitor throughout the production processes with specific productivities increased up to 110 pg/cell/day. Additionally, the product quality attributes of the mAb, with regard to high molecular weight (HMW) and glycan profile, are not negatively impacted. In fact, high mannose is decreased after treatment, which is in contrast to other established growth control methods such as reducing culture temperature. Microarray analysis showed major differences in expression of regulatory genes of the glycosylation and cell cycle signaling pathways between these different growth control methods. Overall, our observations showed that cell cycle arrest by directly targeting CDK4/6 using selective inhibitor compound can be utilized consistently and rapidly to optimize process parameters, such as cell growth, qP, and glycosylation profile in

  13. Critical role of △DNMT3B4/2 in regulating RASSF1A promoter specific DNA methylation in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Shu-hang; LIU Nin-hong; WANG Jie; BAI Hua; MAO Li


    Background △DNMT3B (a new DNMT3B subfamily) expression is initiated through a novel promoter.We identified at least 7 transcription variants of △DNMT3B as a result of alternative pre-mRNA processing.The aim of this study was to detect the expression pattern of △DNMT3B variants in non-small cell lung cancer (NSCLC) and to explore the role of △DNMT3B variants in regulating the promoter-specific DNA methylation.Methods Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual △DNMT3B variants according to their splicing pattems.The expressions of seven △DNMT3B variants were measured in 13 cell lines,109 NSCLC patients,and the corresponding normal lung tissues using reverse transcription-PCR (RT-PCR).The status of the p16 and RASSF1A promoter methylations in the tumors was detected using a methylation specific PCR (MSP).The relationships of the expression patterns of the △DNMT3B variants were analyzed by observing the status of p16 and RASSF1A promoter methylations in the tumors.The siRNA and the anti-sense oligo-dioxynucleotide specifically targeting the junction of exon 5 and 7 of △DNMT3B were designed and transfected by lipofectmane 2000 into H1299 and H358 cell lines.RASSF1A promoter methylation from cells treated by siRNA-△DNMT3B4/2 was detected using MSP and Bisulfite sequencing,and Western blotting was used to detect the protein expression of DNMT3B and △DNMT3B.Cell growth and cell cycle distribution were measured by applying real-time cell growth analysis and flowcytometry,respectively.Results △DNMT3B variants,not DNMT3B,were the predominant transcripts in both NSCLC cell lines and primary tumors.The expression of △DNMT3B4 strongly correlated to the promoter methylation status of RASSFIA in a primary NSCLC.The knockdown of △DNMT3B4/2 by RNA-interference or anti-sense approaches resulted in a complete demethylation of RASSF1A promoter with the reactJvation of a RASSFIA gene expression in less than 12

  14. Discovery of a Small-Molecule Inhibitor of Protein-MicroRNA Interaction Using Binding Assay with a Site-Specifically Labeled Lin28. (United States)

    Lim, Donghyun; Byun, Wan Gi; Koo, Ja Young; Park, Hankum; Park, Seung Bum


    MicroRNAs (miRNAs) regulate gene expression by targeting protein-coding transcripts that are involved in various cellular processes. Thus, miRNA biogenesis has been recognized as a novel therapeutic target. Especially, the let-7 miRNA family is well-known for its tumor suppressor functions and is downregulated in many cancer cells. Lin28 protein binds to let-7 miRNA precursors to inhibit their maturation. Herein, we developed a FRET-based, high-throughput screening system to identify small-molecule inhibitors of the Lin28-let-7 interaction. We employed unnatural amino acid mutagenesis and bioorthogonal chemistry for the site-specific fluorescent labeling of Lin28, which ensures the robustness and reliability of the FRET-based protein-miRNA binding assay. Using this direct binding assay, we identified an inhibitor of the oncogenic Lin28-let-7 interaction. The inhibitor enhanced the production of let-7 miRNAs in Lin28-expressing cancer cells and reduced the level of let-7 target oncogene products.

  15. In Situ Dynamics of F-Specific RNA Bacteriophages in a Small River: New Way to Assess Viral Propagation in Water Quality Studies. (United States)

    Fauvel, Blandine; Gantzer, Christophe; Cauchie, Henry-Michel; Ogorzaly, Leslie


    The occurrence and propagation of enteric viruses in rivers constitute a major public health issue. However, little information is available on the in situ transport and spread of viruses in surface water. In this study, an original in situ experimental approach using the residence time of the river water mass was developed to accurately follow the propagation of F-specific RNA bacteriophages (FRNAPHs) along a 3-km studied river. Surface water and sediment of 9 sampling campaigns were collected and analyzed using both infectivity and RT-qPCR assays. In parallel, some physico-chemical variables such as flow rate, water temperature, conductivity and total suspended solids were measured to investigate the impact of environmental conditions on phage propagation. For campaigns with low flow rate and high temperature, the results highlight a decrease of infectious phage concentration along the river, which was successfully modelled according to a first-order negative exponential decay. The monitoring of infectious FRNAPHs belonging mainly to the genogroup II was confirmed with direct phage genotyping and total phage particle quantification. Reported k decay coefficients according to exponential models allowed for the determination of the actual in situ distance and time necessary for removing 90 % of infectious phage particles. This present work provides a new way to assess the true in situ viral propagation along a small river. These findings can be highly useful in water quality and risk assessment studies to determine the viral contamination spread from a point contamination source to the nearest recreational areas.

  16. Paclitaxel alters the expression and specific activity of deoxycytidine kinase and cytidine deaminase in non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Patel Shitalben R


    Full Text Available Abstract Background We observed that paclitaxel altered the pharmacokinetic properties of gemcitabine in patients with non-small cell lung cancer (NSCLC and limited the accumulation of gemcitabine and its metabolites in various primary and immortalized human cells. Therefore, we classified the drug-drug interaction and the effects of paclitaxel on deoxycytidine kinase (dCK and cytidine deaminase (CDA in three NSCLC cell lines. These enzymes are responsible for the metabolism of gemcitabine to its deaminated metabolite dFdU (80% of the parent drug and the phosphorylated metabolites dFdCMP, dFdCDP and dFdCTP. These metabolites appear to relate to sensitivity and tolerability of gemcitabine based on previous animal and laboratory studies. Methods Three immortalized human cells representative of the most common histological subtypes identified in patients with advanced NSCLC were exposed to the individual drugs or combinations to complete a multiple drug effect analysis. These same cell lines were exposed to vehicle-control or paclitaxel and the mRNA levels, protein expression and specific activity of dCK and CDA were compared. Comparisons were made using a two-tailed paired t-test or analysis of variance with a P value of Results The multiple drug effect analysis indicated synergy for H460, H520 and H838 cells independent of sequence. As anticipated, paclitaxel-gemcitabine increased the number of G2/M cells, whereas gemcitabine-paclitaxel increased the number of G0/G1 or S cells. Paclitaxel significantly decreased dCK and CDA mRNA levels in H460 and H520 cells (40% to 60%, P Conclusion In summary, paclitaxel altered the mRNA levels and specific activity of dCK and CDA and these effects could be dependent on histological subtype. More cell and animal studies are needed to further characterize the relationship between mRNA levels and the overall drug-drug interaction and the potential to use histological subtype as a predictive factor in the

  17. Predictive and prognostic value of preoperative serum tumor markers is EGFR mutation-specific in resectable non-small-cell lung cancer (United States)

    Jiang, Richeng; Wang, Xinyue; Li, Kai


    Background The predictive and prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), squamous cell carcinoma antigen (SCCA) and neuron-specific enolase (NSE) has been investigated in non-small-cell lung cancer (NSCLC) patients. However, few studies have directly focused on the association between these markers and epidermal growth factor receptor (EGFR) mutation status or mutation subtypes. Patients and methods We retrospectively analyzed 1016 patients with stage I-IIIA NSCLC who underwent complete resection between 2008 and 2012. Correlations between serum tumor marker levels and EGFR mutations and survival parameters were analyzed and prognostic factors were identified. Results Cyfra21-1 levels (P = 0.032 for disease-free survival [DFS]; P < 0.001 for overall survival [OS]) and clinical stage were identified as independent predictive and prognostic factors in EGFR-mutated adenocarcinoma patients. CEA levels (P < 0.001 for DFS; P = 0.002 for OS) and clinical stage were independently predictive and prognostic in EGFR wild-type adenocarcinoma patients. Further stratification analysis revealed that in EGFR exon 19 deletion adenocarcinomas, elevated Cyfra21-1 was an independent prognostic factor (P = 0.002). Within the Leu858Arg substitution subgroup, increased CEA (P = 0.005) and clinical stage were predictive factors of DFS, while elevated CEA (P = 0.005) and Cyfra21-1 (P = 0.027) were independent prognostic factors. Conclusion Cyfra21-1 and CEA exhibit different predictive and prognostic values between EGFR-mutated and wild-type adenocarcinomas, as well as between EGFR mutation subtypes. The prognostic impact of preoperative serum tumor markers should be evaluated together with EGFR mutation status. PMID:27072585

  18. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen


    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine de...

  19. Specific Regional and Age-Related Small Noncoding RNA Expression Patterns Within Superior Temporal Gyrus of Typical Human Brains Are Less Distinct in Autism Brains (United States)

    Stamova, Boryana; Ander, Bradley P.; Barger, Nicole; Sharp, Frank R.


    Small noncoding RNAs play a critical role in regulating messenger RNA throughout brain development and when altered could have profound effects leading to disorders such as autism spectrum disorders (ASD). We assessed small noncoding RNAs, including microRNA and small nucleolar RNA, in superior temporal sulcus association cortex and primary auditory cortex in typical and ASD brains from early childhood to adulthood. Typical small noncoding RNA expression profiles were less distinct in ASD, both between regions and changes with age. Typical micro-RNA coexpression associations were absent in ASD brains. miR-132, miR-103, and miR-320 micro-RNAs were dysregulated in ASD and have previously been associated with autism spectrum disorders. These diminished region- and age-related micro-RNA expression profiles are in line with previously reported findings of attenuated messenger RNA and long noncoding RNA in ASD brain. This study demonstrates alterations in superior temporal sulcus in ASD, a region implicated in social impairment, and is the first to demonstrate molecular alterations in the primary auditory cortex. PMID:26350727

  20. Species-specific impacts of a small marine reserve on reef fish production and fishing productivity in the Turks and Caicos Islands

    NARCIS (Netherlands)

    Tupper, M.H.; Rudd, M.A.


    Marine reserves are widely considered to potentially benefit reef fisheries through emigration, yet the empirical basis for predicting the extent of this for small reserves is weak. The effects of fishing pressure and habitat on biomass and catch per unit effort (CPUE) of three species of exploited

  1. Species-specific impacts of a small marine reserve on reef fish production and fishing productivity in the Turks and Caicos Islands


    Tupper, M.H.; Rudd, M.A.


    Marine reserves are widely considered to potentially benefit reef fisheries through emigration, yet the empirical basis for predicting the extent of this for small reserves is weak. The effects of fishing pressure and habitat on biomass and catch per unit effort (CPUE) of three species of exploited reef fish were studied at South Caicos, Turks and Caicos Islands. Distribution and abundance of hogfish (Lachnolaimus maximus) and white margate (Haemulon album) were inversely correlated with cove...

  2. MISSEL: a method to identify a large number of small species-specific genomic subsequences and its application to viruses classification. (United States)

    Fiscon, Giulia; Weitschek, Emanuel; Cella, Eleonora; Lo Presti, Alessandra; Giovanetti, Marta; Babakir-Mina, Muhammed; Ciotti, Marco; Ciccozzi, Massimo; Pierangeli, Alessandra; Bertolazzi, Paola; Felici, Giovanni


    Continuous improvements in next generation sequencing technologies led to ever-increasing collections of genomic sequences, which have not been easily characterized by biologists, and whose analysis requires huge computational effort. The classification of species emerged as one of the main applications of DNA analysis and has been addressed with several approaches, e.g., multiple alignments-, phylogenetic trees-, statistical- and character-based methods. We propose a supervised method based on a genetic algorithm to identify small genomic subsequences that discriminate among different species. The method identifies multiple subsequences of bounded length with the same information power in a given genomic region. The algorithm has been successfully evaluated through its integration into a rule-based classification framework and applied to three different biological data sets: Influenza, Polyoma, and Rhino virus sequences. We discover a large number of small subsequences that can be used to identify each virus type with high accuracy and low computational time, and moreover help to characterize different genomic regions. Bounding their length to 20, our method found 1164 characterizing subsequences for all the Influenza virus subtypes, 194 for all the Polyoma viruses, and 11 for Rhino viruses. The abundance of small separating subsequences extracted for each genomic region may be an important support for quick and robust virus identification. Finally, useful biological information can be derived by the relative location and abundance of such subsequences along the different regions.

  3. Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy. (United States)

    Kobayashi, Makoto; Ikezoe, Takayuki; Uemura, Yoshiki; Takeuchi, Tamotsu; Ueno, Hisayuki; Ohtsuki, Yuji; Taguchi, Hirokuni


    We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.

  4. In vivo screening of modified siRNAs for non-specific antiviral effect in a small fish model: number and localization in the strands are important

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Bramsen, Jesper Bertram; Pakula, Malgorzata Maria;


    but often only examining the expression of specific immunologically relevant genes in selected cell populations typically blood cells from treated animals or humans. Assays using a relevant physiological state in biological models as read-out are not common. Here we use a fish model where the innate......, increase the antiviral effect of siRNAs. The applied fish model represents a potent tool for conducting fast but statistically and scientifically relevant evaluations of chemically optimized siRNAs with respect to non-specific antiviral effects in vivo....

  5. Molecular Detection of Neuron-Specific ELAV-Like-Positive Cells in the Peripheral Blood of Patients with Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vito D’Alessandro


    Full Text Available Background: n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision-like genes belong to a family codifying for onconeural RNA-binding proteins. Anti-Hu-antibodies (anti-Hu-Ab are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN, and low titres of anti-Hu-Ab, were found in newly diagnosed Small Cell Lung Cancer (SCLC. The aim of this study is to develop a sensitive and quantitative molecular real-time PCR assay to detect SCLC cells in peripheral blood (PB through nELAV-like transcripts quantification.

  6. 1 kb of the lactase-phlorizin hydrolase promoter directs post-weaning decline and small intestinal-specific expression in transgenic mice

    DEFF Research Database (Denmark)

    Troelsen, J T; Mehlum, A; Spodsberg, N


    Adult-type hypolactasia is a genetic condition making approximately one half of the human population intolerant to milk because of abdominal symptoms. The cause is a post-weaning down-regulation of the intestinal-specific enzyme lactase-phlorizin hydrolase (LPH) reducing the intestinal capacity...

  7. The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. (United States)

    Pereira-Leal, J B; Seabra, M C


    The Rab/Ypt/Sec4 family forms the largest branch of the Ras superfamily of GTPases, acting as essential regulators of vesicular transport pathways. We used the large amount of information in the databases to analyse the mammalian Rab family. We defined Rab-conserved sequences that we designate Rab family (RabF) motifs using the conserved PM and G motifs as "landmarks". The Rab-specific regions were used to identify new Rab proteins in the databases and suggest rules for nomenclature. Surprisingly, we find that RabF regions cluster in and around switch I and switch II regions, i.e. the regions that change conformation upon GDP or GTP binding. This finding suggests that specificity of Rab-effector interaction cannot be conferred solely through the switch regions as is usually inferred. Instead, we propose a model whereby an effector binds to RabF (switch) regions to discriminate between nucleotide-bound states and simultaneously to other regions that confer specificity to the interaction, possibly Rab subfamily (RabSF) specific regions that we also define here. We discuss structural and functional data that support this model and its general applicability to the Ras superfamily of proteins.

  8. Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches (United States)

    Ajandouz, El Hassan; Berdah, Stéphane; Moutardier, Vincent; Bege, Thierry; Birnbaum, David Jérémie; Perrier, Josette; Di Pasquale, Eric; Maresca, Marc


    In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans. PMID:27483321

  9. Comparative analysis of virus-specific small RNA profiles of three biologically distinct strains of Potato virus Y in infected potato (Solanum tuberosum) cv. Russet Burbank. (United States)

    Naveed, Khalid; Mitter, Neena; Harper, Artemus; Dhingra, Amit; Pappu, Hanu R


    Deep sequencing technology has enabled the analysis of small RNA profiles of virus-infected plants and could provide insights into virus-host interactions. Potato virus Y is an economically important viral pathogen of potato worldwide. In this study, we investigated the nature and relative levels of virus-derived small interfering RNAs (vsiRNAs) in potato cv. Russet Burbank infected with three biologically distinct and economically important strains of PVY, the ordinary strain (PVY-O), tobacco veinal-necrotic strain (PVY-N) and tuber necrotic strain (PVY-NTN). The analysis showed an overall abundance of vsiRNAs of 20-24nt in PVY-infected plants. Considerable differences were present in the distribution of vsiRNAs as well as total small RNAs. The 21nt class was the most prevalent in PVY-infected plants irrespective of the virus strain, whereas in healthy potato plants, the 24nt class was the most dominant. vsiRNAs were derived from every position in the PVY genome, though certain hotspots were identified for each of the PVY strains. Among the three strains used, the population of vsiRNAs of different size classes was relatively different with PVY-NTN accumulating the highest level of vsiRNAs, while PVY-N infected plants had the least population of vsiRNAs. Unique vsiRNAs mapping to PVY genome in PVY-infected plants amounted to 3.13, 1.93 and 1.70% for NTN, N and O, respectively. There was a bias in the generation of vsiRNAs from the plus strand of the genome in comparison to the negative strand. The highest number of total vsiRNAs was from the cytoplasmic inclusion protein gene (CI) in PVY-O and PVY-NTN strains, whereas from PVY-N, the NIb gene produced maximum total vsiRNAs. These findings indicate that the three PVY strains interact differently in the same host genetic background and provided insights into virus-host interactions in an important food crop.

  10. Selectivity and specificity of small molecule fluorescent dyes/probes used for the detection of Zn2+ and Ca2+ in cells. (United States)

    Figueroa, Julio A Landero; Vignesh, Kavitha Subramanian; Deepe, George S; Caruso, Joseph


    Fluorescent dyes are widely used in the detection of labile (free or exchangeable) Zn(2+) and Ca(2+) in living cells. However, their specificity over other cations and selectivity for detection of labile vs. protein-bound metal in cells remains unclear. We characterized these important properties for commonly used Zn(2+) and Ca(2+) dyes in a cellular environment. By tracing the fluorescence emission signal along with UV-Vis and size exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS) in tandem, we demonstrated that among the dyes used for Zn(2+), Zinpyr-1 fluoresces in the low molecular mass (LMM) region containing labile Zn(2+), but also fluoresces in different molecular mass regions where zinc ion is detected. However, FluoZin™-3 AM, Newport Green™ DCF and Zinquin ethyl ester display weak fluorescence, lack of metal specificity and respond strongly in the high molecular mass (HMM) region. Four Ca(2+) dyes were studied in an unperturbed cellular environment, and two of these were tested for binding behavior under an intracellular Ca(2+) release stimulus. A majority of Ca(2+) was in the labile form as tested by SEC-ICP-MS, but the fluorescence from Calcium Green-1™ AM, Oregon Green® 488 BAPTA-1, Fura red™ AM and Fluo-4 NW dyes in cells did not correspond to free Ca(2+) detection. Instead, the dyes showed non-specific fluorescence in the mid- and high-molecular mass regions containing Zn, Fe and Cu. Proteomic analysis of one of the commonly seen fluorescing regions showed the possibility for some dyes to recognize Zn and Cu bound to metallothionein 2. These studies indicate that Zn(2+) and Ca(2+) binding dyes manifest fluorescence responses that are not unique to recognition of labile metals and bind other metals, leading to suboptimal specificity and selectivity.

  11. [Tissue-specific reaction of the mucous coat of herbals' small gut under the influence of spaceflight factors on board biosat "Foton M3"]. (United States)

    Atiakshin, D A; Bykov, E G; Il'in, E A; Pashkov, A N


    Methods of light-optical microscopy, morpho- and cytometry and histochemisty were used to study the epithelial lining of herbal's small gut after 12-day flight in biosat "Foton M3". Changes in mucous coat histoarchitectonics included branching of villi and cystic lumps lined with prismatic epithelium. Shortening of the mucous membrane villi was accompanied by reduction of prismatic epithelium height, increase in the number of goblet cells and change of their dislocation, stimulation of excretion of biosynthesis products on the brush border surface pointing to impairment of the interstitial barrier function. Nothing evidenced change in mitotic index of the crypts epithelium in animals of the vivarium control, in the Kontur facility simulating the flight condition, and in the space flown herbals. There was a minor individual variability of changes in the epithelium mucous membrane due to the simulated flight factors.

  12. Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size of Amino Acid by Decreasing Expression of Specific Transporters in the Small Intestine (United States)

    Luo, Min; Zhang, Xin; Sun, Wen Juan; Jiao, Ning; Li, De Fa; Yin, Jing Dong


    Dietary protein restriction is not only beneficial to health and longevity in humans, but also protects against air pollution and minimizes feeding cost in livestock production. However, its impact on amino acid (AA) absorption and metabolism is not quite understood. Therefore, the study aimed to explore the effect of protein restriction on nitrogen balance, circulating AA pool size, and AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 ± 1.5 kg were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial. Growth (n = 24), nitrogen balance (n = 6), and the expression of small intestinal AA and peptide transporters (n = 6) were evaluated. In Exp.2, 12 barrows weighting 22.7 ± 1.3 kg were surgically fitted with catheters in the portal and jejunal veins as well as the carotid artery and assigned to a diet containing 14 or 18% CP. A series of blood samples were collected before and after feeding for determining the pool size of circulating AA and AA absorption in the portal vein, respectively. Protein restriction did not sacrifice body weight gain and protein retention, since nitrogen digestibility was increased as dietary protein content reduced. However, the pool size of circulating AA except for lysine and threonine, and most AA flux through the portal vein were reduced in pigs fed the low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1) was stimulated, but the expression of the neutral and cationic AA transporter systems was depressed. These results evidenced that protein restriction with essential AA-balanced diets, decreased AA absorption and reduced circulating AA pool size. Increased expression of small intestinal peptide transporter PepT-1 could not compensate for the depressed expression of jejunal AA transporters for AA absorption. PMID:27611307

  13. Protein Restriction with Amino Acid-Balanced Diets Shrinks Circulating Pool Size of Amino Acid by Decreasing Expression of Specific Transporters in the Small Intestine. (United States)

    Qiu, Kai; Qin, Chun Fu; Luo, Min; Zhang, Xin; Sun, Wen Juan; Jiao, Ning; Li, De Fa; Yin, Jing Dong


    Dietary protein restriction is not only beneficial to health and longevity in humans, but also protects against air pollution and minimizes feeding cost in livestock production. However, its impact on amino acid (AA) absorption and metabolism is not quite understood. Therefore, the study aimed to explore the effect of protein restriction on nitrogen balance, circulating AA pool size, and AA absorption using a pig model. In Exp.1, 72 gilts weighting 29.9 ± 1.5 kg were allocated to 1 of the 3 diets containing 14, 16, or 18% CP for a 28-d trial. Growth (n = 24), nitrogen balance (n = 6), and the expression of small intestinal AA and peptide transporters (n = 6) were evaluated. In Exp.2, 12 barrows weighting 22.7 ± 1.3 kg were surgically fitted with catheters in the portal and jejunal veins as well as the carotid artery and assigned to a diet containing 14 or 18% CP. A series of blood samples were collected before and after feeding for determining the pool size of circulating AA and AA absorption in the portal vein, respectively. Protein restriction did not sacrifice body weight gain and protein retention, since nitrogen digestibility was increased as dietary protein content reduced. However, the pool size of circulating AA except for lysine and threonine, and most AA flux through the portal vein were reduced in pigs fed the low protein diet. Meanwhile, the expression of peptide transporter 1 (PepT-1) was stimulated, but the expression of the neutral and cationic AA transporter systems was depressed. These results evidenced that protein restriction with essential AA-balanced diets, decreased AA absorption and reduced circulating AA pool size. Increased expression of small intestinal peptide transporter PepT-1 could not compensate for the depressed expression of jejunal AA transporters for AA absorption.

  14. Association of Lung Inflammatory Cells with Small Airways Function and Exhaled Breath Markers in Smokers - Is There a Specific Role for Mast Cells?

    Directory of Open Access Journals (Sweden)

    Yvonne Nussbaumer-Ochsner

    Full Text Available Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath.Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test, measurement of fractional exhaled nitric oxide (FeNO and pH/8-isoprostane in exhaled breath condensate (EBC. Lung tissue sections containing cancer-free large (LA and small airways (SA were stained for inflammatory cells. Mucosal (MCT respectively connective tissue mast cells (MCTC and interleukin-17A (IL-17A expression by mast cells was analysed using a double-staining protocol.The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances. IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39, for the FEV1% pred. (rs= 0.37 and for FEV1/FVC ratio (rs=0.38 with MCT in SA (P<0.05 for all instances. 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44, there was no correlation for pH or FeNO with cellular distribution in SA.Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the

  15. Small-Scale Habitat-Specific Variation and Adaptive Divergence of Photosynthetic Pigments in Different Alkali Soils in Reed Identified by Common Garden and Genetic Tests (United States)

    Qiu, Tian; Jiang, LiLi; Li, ShanZhi; Yang, YunFei


    Flexibility of photosynthetic pigment traits is an important adaptive mechanism through which plants can increase mean fitness in a variable environment. Unlike morphological traits in plants, photosythesis has been shown to exhibit phenotypic plasticity, responding rapidly to environmental conditions. Meanwhile, local adaptation at small scales is considered to be rare. Thus, detecting the small-scale adaptive divergence of photosynthetic pigments presents a challenge. Leaf concentrations of photosynthetic pigments under stressful conditions may be reduced or maintained. Concentrations of some pigments and/or ratio of Chlorophyll a (Chla) to Chlorophyll b (Chlb) do not change markedly in some species, such as the common reed, Phragmites australis, a cosmopolitan grass and common invader. Little is known about photosynthetic responses of this plant to varying levels of alkali salt. Few studies have attempted to account for the relationship between pigment accumulation and leaf position in wild plant populations in grasslands. In this study, photosynthetic pigment concentrations and the total Chl(a+b)/Car ratio decreased as the growing season progressed and were shown to be significantly lower in the habitat with a higher soil pH value and less moisture when compared between habitats. The Chla/Chlb ratio did not differ significantly between habitats, although it increased significantly over time. Leaves in the middle position may be functionally important in the response to soil conditions because only pigment concentrations and the Chl(a+b)/Car ratio of those leaves varied between habitats significantly. The outlier loci, used to evaluate molecular signatures of selection, were detected by Arlequin, Bayescan, and Bayenv analyses. In the simulated habitats of common garden, the local genotypes had higher values of Chla, Chlb, Chl(a+b), Car in their home habitat than did genotypes originating from the other habitat. QST–FST comparisons provided evidence of

  16. Assessing, mapping and validating site-specific ecotoxicological risk for pesticide mixtures: a case study for small scale hot spots in aquatic and terrestrial environments. (United States)

    Vaj, Claudia; Barmaz, Stefania; Sørensen, Peter Borgen; Spurgeon, David; Vighi, Marco


    Mixture toxicity is a real world problem and as such requires risk assessment solutions that can be applied within different geographic regions, across different spatial scales and in situations where the quantity of data available for the assessment varies. Moreover, the need for site specific procedures for assessing ecotoxicological risk for non-target species in non-target ecosystems also has to be recognised. The work presented in the paper addresses the real world effects of pesticide mixtures on natural communities. Initially, the location of risk hotspots is theoretically estimated through exposure modelling and the use of available toxicity data to predict potential community effects. The concept of Concentration Addition (CA) is applied to describe responses resulting from exposure of multiple pesticides The developed and refined exposure models are georeferenced (GIS-based) and include environmental and physico-chemical parameters, and site specific information on pesticide usage and land use. As a test of the risk assessment framework, the procedures have been applied on a suitable study areas, notably the River Meolo basin (Northern Italy), a catchment characterised by intensive agriculture, as well as comparative area for some assessments. Within the studied areas, the risks for individual chemicals and complex mixtures have been assessed on aquatic and terrestrial aboveground and belowground communities. Results from ecological surveys have been used to validate these risk assessment model predictions. Value and limitation of the approaches are described and the possibilities for larger scale applications in risk assessment are also discussed.

  17. A small RNA mediated regulation of a stress-activated retrotransposon and the tissue specific transposition during the reproductive period in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Wataru eMatsunaga


    Full Text Available Transposable elements (TEs are key elements that facilitate genome evolution of the host organism. A number of studies have assessed the functions of TEs, which change gene expression in the host genome. Activation of TEs is controlled by epigenetic modifications such as DNA methylation and histone modifications. Several recent studies have reported that TEs can also be activated by biotic or abiotic stress in some plants. We focused on a Ty1/copia retrotransposon, ONSEN, that is activated by heat stress in Arabidopsis. We found that transcriptional activation of ONSEN was regulated by an siRNA-related pathway, and the activation could also be induced by oxidative stress. Mutants deficient in small interfering RNA (siRNA biogenesis that were exposed to heat stress at the initial stages of vegetative growth showed transgenerational transposition. The transposition was also detected in the progeny, which originated from tissue that had differentiated after exposure to the heat stress. The results indicated that in some undifferentiated cells, transpositional activity could be maintained quite long after exposure to the heat stress.

  18. Analysis of the small non-protein-coding RNA profile of mouse spermatozoa reveals specific enrichment of piRNAs within mature spermatozoa. (United States)

    Hutcheon, Kate; McLaughlin, Eileen A; Stanger, Simone J; Bernstein, Ilana R; Dun, Matthew D; Eamens, Andrew L; Nixon, Brett


    Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality and fertilization competence. Here we demonstrate that mouse spermatozoa possess a complex small non-protein-coding RNA (sRNA) profile, the composition of which is markedly influenced by their epididymal transit. Thus, although miRNAs are highly represented in the spermatozoa of the proximal epididymis, this sRNA class is largely diminished in mature spermatozoa of the distal epididymis. Coincident with this, a substantial enrichment in Piwi-interacting RNA (piRNA) abundance in cauda spermatozoa was detected. Further, features of cauda piRNAs, including; predominantly 29-31 nts in length; preference for uracil at their 5' terminus; no adenine enrichment at piRNA nt 10, and; predominantly mapping to intergenic regions of the mouse genome, indicate that these piRNAs are generated by the PIWIL1-directed primary piRNA production pathway. Accordingly, PIWIL1 was detected via immunoblotting and mass spectrometry in epididymal spermatozoa. These data provide insight into the complexity and dynamic nature of the sRNA profile of spermatozoa and raise the intriguing prospect that piRNAs are generated in situ in maturing spermatozoa. Such information is of particular interest in view of the potential role for paternal sRNAs in influencing conception, embryo development and intergenerational inheritance.

  19. Focus E-learning on Specific Small Target Groups (doi: 10.3991/ijac.v1i2.536

    Directory of Open Access Journals (Sweden)

    Vivek Ratna


    Full Text Available We hear criticism about the education system in several countries. It’s been said that schools and many institutions are experimenting with several old methods of education that are not founded on scientific grounds but on (political beliefs. Many organizations still deliver training in classrooms or push standard content via the internet to individual employees. In 2005 Bill Gates called secondary schools an outdated tool for the training of tomorrow’s workforce. This paper about e-learning and e-development will show trends in technology and in learning and cooperative behaviors. All these and other factors have an influence on effective learning. It deals with the importance of content-driven and small professionally coached online workgroups supporting a practical guided learning process through questions. This is a promising development that can take away many threats of the current education in schools and Organizations. Also, this approach shows under what conditions the concept of Life Long Learning can be successful. Organizations will have to pursue this if they wish to overcome ‘the battle for the hard to find well educated employee’. The conclusion is straight forward: formulate clear targets for formal and informal learning, know your audience, listen and create for them recognizable conditions and measure the ROI.

  20. Diagnostic accuracy of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging of small renal masses in real practice: sensitivity and specificity according to subjective radiologic interpretation. (United States)

    Kim, Jae Heon; Sun, Hwa Yeon; Hwang, Jiyoung; Hong, Seong Sook; Cho, Yong Jin; Doo, Seung Whan; Yang, Won Jae; Song, Yun Seob


    The aim of this study was to investigate the diagnostic accuracy of contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) of small renal masses in real practice. Contrast-enhanced CT and MRI were performed between February 2008 and February 2013 on 68 patients who had suspected small (≤4 cm) renal cell carcinoma (RCC) based on ultrasonographic measurements. CT and MRI radiographs were reviewed, and the findings of small renal masses were re-categorized into five dichotomized scales by the same two radiologists who had interpreted the original images. Receiver operating characteristics curve analysis was performed, and sensitivity and specificity were determined. Among the 68 patients, 60 (88.2 %) had RCC and eight had benign disease. The diagnostic accuracy rates of contrast-enhanced CT and MRI were 79.41 and 88.23 %, respectively. Diagnostic accuracy was greater when using contrast-enhanced MRI because too many masses (67.6 %) were characterized as "4 (probably solid cancer) or 5 (definitely solid cancer)." The sensitivity of contrast-enhanced CT and MRI for predicting RCC were 79.7 and 88.1 %, respectively. The specificities of contrast-enhanced CT and MRI for predicting RCC were 44.4 and 33.3 %, respectively. Fourteen diagnoses (20.5 %) were missed or inconsistent compared with the final pathological diagnoses. One appropriate nephroureterectomy and five unnecessary percutaneous biopsies were performed for RCC. Seven unnecessary partial nephrectomies were performed for benign disease. Although contrast-enhanced CT and MRI showed high sensitivity for detecting small renal masses, specificity remained low.

  1. 3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue. (United States)

    Pedersen, Peter L


    Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent

  2. Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

    Directory of Open Access Journals (Sweden)

    Bakonyi Neto Alexandre


    Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

  3. Silencing of advanced glycosylation and glycosylation and product-specific receptor (RAGE) inhibits the metastasis and growth of non-small cell lung cancer. (United States)

    Yu, Yan Xia; Pan, Wen Chong; Cheng, Yu Feng


    Non-small cell lung cancer (NSCLC) constitutes the main cases of lung cancer and is the world's most common and lethal cancer owing to regional invasion or distant metastasis. Growing morbidity and lethality demonstrates that valid molecular target in management of NSCLC metastasis is still absence. The receptor of advanced glycation end-products (RAGE) has been identified as an oncogenic gene and appears to promote the growth and metastasis of various cancers. Here, we investigated if RAGE targeted by RNA interference (RNAi) might have certain effect on the restraint of the growth of NSCLC and tumor metastasis. Wound healing and Transwell invasion assays indicated that RAGE favored the metastatic capabilities of NSCLC H1975 cells. Besides, soft-agar colony assay revealed that silencing RAGE significantly blocked colony-forming capability of H1975 cells in vitro. Furthermore, we observed that RAGE participated in H1975 cells growth, metastasis and epithelial-mesenchymal transition (EMT) by regulating interdict crux intracellular signaling pathways, including phosphatidylinositol-3 kinase/serine-threonine kinase (PI3K/AKT) and V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog/RAF proto-oncogene serine/threonine-protein kinase (KRAS/RAF-1). In xenograft model, significantly reduction intumor growth and Ki67 expression was demonstrated in nude mice inoculation with RAGE down-regulation H1975 cells. To conclude, our study demonstrated that RAGE played a crucial role in the metastasis and growth of NSCLC by regulating PI3K/AKT and KRAS/RAF-1 signaling pathways, thereby might be a promising therapeutic target for NSCLC.

  4. Specific cation interactions as the cause of slow dynamics and hysteresis in dye and perovskite solar cells: a small-perturbation study. (United States)

    Contreras, Lidia; Idígoras, Jesús; Todinova, Anna; Salado, Manuel; Kazim, Samrana; Ahmad, Shahzada; Anta, Juan A


    Hysteresis is one of the most remarkable features of perovskite solar cells; however, it is also present in other kinds of devices such as dye-sensitized solar cells. Hysteresis is due to underlying slow dynamic processes that interfere with the process of charge separation which depends critically on the selective contacts used. In this work we focus on the low-frequency (0.1-10 Hz) dynamics using impedance and intensity-modulated photocurrent spectroscopy and found that both perovskite solar cells (PSCs) and "viscous electrolyte containing" dye-sensitized solar cells (DSSCs) can be described on the same fundamental grounds. By comparing different electrolyte compositions in DSSCs and both methylammonium and formamidinium-based PSCs, we find a connection between the polar nature of the cations and the low-frequency component of these solar cells. There is evidence that in both cases ion transport and specific chemical interactions with the TiO2 surface give rise to the slow dynamics and the hysteresis. This is mainly inferred from the slope of the capacitance vs. applied voltage which shows accumulation behavior for the formulations with higher dipole moments only.

  5. Controlling the specificity of modularly assembled small molecules for RNA via ligand module spacing: targeting the RNAs that cause myotonic muscular dystrophy. (United States)

    Lee, Melissa M; Childs-Disney, Jessica L; Pushechnikov, Alexei; French, Jonathan M; Sobczak, Krzysztof; Thornton, Charles A; Disney, Matthew D


    tetramer also bind approximately 13- and approximately 63-fold more tightly to DM1 RNAs than does MBNL1. The modularly assembled compounds are cell permeable and nontoxic as determined by flow cytometry. The results establish that for these two systems: (i) a programmable modular assembly approach can provide synthetic ligands for RNA with affinities and specificities that exceed those of natural proteins; and, (ii) the spacing of ligand modules can be used to tune specificity for one RNA target over another.

  6. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. (United States)

    Valsasina, Barbara; Beria, Italo; Alli, Cristina; Alzani, Rachele; Avanzi, Nilla; Ballinari, Dario; Cappella, Paolo; Caruso, Michele; Casolaro, Alessia; Ciavolella, Antonella; Cucchi, Ulisse; De Ponti, Anna; Felder, Eduard; Fiorentini, Francesco; Galvani, Arturo; Gianellini, Laura M; Giorgini, Maria L; Isacchi, Antonella; Lansen, Jaqueline; Pesenti, Enrico; Rizzi, Simona; Rocchetti, Maurizio; Sola, Francesco; Moll, Jürgen


    Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings.

  7. Mutations affecting lysine-35 of gpNu1, the small subunit of bacteriophage lambda terminase, alter the strength and specificity of holoterminase interactions with DNA. (United States)

    Hwang, Y; Feiss, M


    The small subunit of lambda terminase, gpNu1, contains a low-affinity ATPase activity that is stimulated by nonspecific dsDNA. The location of the gpNu1 ATPase center is suggested by a sequence match between gpNu1 (29-VLRGGGKG-36) and the phosphate-binding loop, or P-loop (GXXXXGKT/S), of known ATPase. The proposed P-loop of gpNu1 is just downstream of a putative helix-turn-helix DNA-binding motif, located between residues 5 and 24. Published work has shown that changing lysine-35 of the proposed P-loop of gpNu1 alters the response of the ATPase activity to DNA, as follows. The changes gpNu1 k35A and gpNu1 K35D increase the level of DNA required for maximal stimulation of the gpNu1 ATPase by factors of 2- and 10-fold, respectively. The maximally stimulated ATPase activities of the mutant enzymes are indistinguishable from that of the wild-type enzyme. In the present work, the effects of changing lysine-35 on the cos-cleavage and DNA-packaging activities of terminase were examined. In vitro, the gpNu1 K35A enzyme cleaved cos as efficiently as the wild-type enzyme, but required a 2-fold increased level of substrate DNA for saturation, suggesting a slight reduction in DNA affinity. In a crude DNA-packaging system using cleaved lambda DNA as substrate, the gpNu1 K35A enzyme had a 10-fold defect. In vivo, lambda Nu1 K35A showed a 2-fold reduction in cos cleavage, but no packaged DNA was detected. The primary defect of the gpNu1 K35A enzyme was concluded to be in a post-cos-cleavage step of DNA packaging. In in vitro cos-cleavage experiments, the gpNu1 K35D enzyme had a 10-fold increased requirement for saturation by substrate DNA. Furthermore, the cos-cleavage activity of gpNu1 K35D enzyme was strongly inhibited by the presence of nonspecific DNA, indicating that the gpNu1 K35D enzyme is unable to discriminate effectively between cos and nonspecific DNA. No cos cleavage was observed in vivo for lambda Nu1 K35D, a result consistent with the discrimination defect found in

  8. Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pøhl, Mette; Olsen, Karen Ege; Holst, Rene


    BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell...... proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7......) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7...

  9. The diagnostic value of small bowel wall vascularity after sulfur hexafluoride-filled microbubble injection in patients with Crohn's disease. Correlation with the therapeutic effectiveness of specific anti-inflammatory treatment

    Energy Technology Data Exchange (ETDEWEB)

    Quaia, Emilio [Department of Radiology, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste (Italy)], E-mail:; Migaleddu, Vincenzo [Sardinian Mediterranean Imaging Research Group - SMIRG no profit foundation, Via Gorizia no 11 07100 Sassari (Italy); Baratella, Elisa; Pizzolato, Riccardo; Rossi, Alexia; Grotto, Maurizio; Cova, Maria Assunta [Department of Radiology, Cattinara Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste (Italy)


    Purpose: To assess the value of small bowel wall vascularity after microbubble contrast agent injection in evaluating the therapeutic effectiveness of specific anti-inflammatory treatment in patients with Crohn's disease. Materials and methods: Fifteen patients (7 male and 8 female; mean age {+-} SD, 40 years {+-} 6) with a biopsy-proven diagnosis of Crohn's disease - Crohn's disease activity index (CDAI) > 150 (n = 12 patients) or <150 (n = 3) - involving the terminal loop of the small bowel (wall thickness >5 mm) were included. In each patient the terminal loop was scanned by contrast-enhanced ultrasound (CEUS) after sulfur hexafluoride-filled microbubble injection before and after 6-month anti-inflammatory treatment. The vascularity of the terminal loop was quantified in gray-scale levels (0-255) by a manually drawn ROI encompassing the thickened bowel wall and it was correlated with CDAI. Result: Before the beginning of the specific treatment all patients revealed diffuse transparietal contrast enhancement after microbubble injection, except for 3 patients who revealed contrast enhancement limited to the submucosa. In 13 patients the slope of the first ascending tract and the area under the enhancement curve were significantly lower after anti-inflammatory treatment (P < 0.05; Wilcoxon test) with a significant correlation with the CDAI score ({rho} = 0.85, P < 0.05). In 2 patients no significant vascularity changes were found even though a mild reduction of CDAI score was identified (from 200 to 150 gray-scale levels). Conclusion: CEUS is a useful method to assess the therapeutic effectiveness of specific medical anti-inflammatory treatment in patients with Crohn's disease.

  10. Small acid-soluble spore proteins of Clostridium acetobutylicum are able to protect DNA in vitro and are specifically cleaved by germination protease GPR and spore protease YyaC. (United States)

    Wetzel, Daniela; Fischer, Ralf-Jörg


    Small acid-soluble proteins (SASPs) play an important role in protection of DNA in dormant bacterial endospores against damage by heat, UV radiation or enzymic degradation. In the genome of the strict anaerobe Clostridium acetobutylicum, five genes encoding SASPs have been annotated and here a further sixth candidate is suggested. The ssp genes are expressed in parallel dependent upon Spo0A, a master regulator of sporulation. Analysis of the transcription start points revealed a σG or a σF consensus promoter upstream of each ssp gene, confirming a forespore-specific gene expression. SASPs were termed SspA (Cac2365), SspB (Cac1522), SspD (Cac1620), SspF (Cac2372), SspH (Cac1663) and Tlp (Cac1487). Here it is shown that with the exception of Tlp, every purified recombinant SASP is able to bind DNA in vitro thereby protecting it against enzymic degradation by DNase I. Moreover, SspB and SspD were specifically cleaved by the two germination-specific proteases GPR (Cac1275) and YyaC (Cac2857), which were overexpressed in Escherichia coli and activated by an autocleavage reaction. Thus, for the first time to our knowledge, GPR-like activity and SASP specificity could be demonstrated for a YyaC-like protein. Collectively, the results assign SspA, SspB, SspD, SspF and SspH of C. acetobutylicum as members of α/β-type SASPs, whereas Tlp seems to be a non-DNA-binding spore protein of unknown function. In acetic acid-extracted proteins of dormant spores of C. acetobutylicum, SspA was identified almost exclusively, indicating its dominant biological role as a major α/β-type SASP in vivo.

  11. Small - Display Cartography

    DEFF Research Database (Denmark)

    Nissen, Flemming; Hvas, Anders; Münster-Swendsen, Jørgen

    This report comprises the work carried out in the work-package of small display cartography. The work-package has aimed at creating a general framework for the small-display cartography. A solid framework facilitates an increased use of spatial data in mobile devices - thus enabling, together...... with the rapidly evolving positioning techniques, a new category of position-dependent, map-based services to be introduced. The report consists of the following parts: Part I: Categorization of handheld devices, Part II: Cartographic design for small-display devices, Part III: Study on the GiMoDig Client ? Portal...... Service Communication and finally, Part IV: Concluding remarks and topics for further research on small-display cartography. Part II includes a separate Appendix D consisting of a cartographic design specification. Part III includes a separate Appendix C consisting of a schema specification, a separate...

  12. Specific Phobias (United States)

    ... Mental Health This information in Spanish ( en español ) Specific phobias Treatment More information on specific phobias A specific ... targeted psychotherapy. Return to top More information on Specific phobias Explore other publications and websites Phobias (Copyright © American ...

  13. Effect of maternal and post weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult Apc+/Min and wild type mice.

    Directory of Open Access Journals (Sweden)

    Jill Ann Mckay


    Full Text Available Increasing evidence supports the developmental origins of adult health and disease hypothesis which argues for a causal relationship between adverse early life nutrition and increased disease risk in adulthood. Modulation of epigenetic marks, e.g. DNA methylation and consequential altered gene expression, has been proposed as a mechanism mediating these effects. Via its role as a methyl donor, dietary folate supply may influence DNA methylation. As aberrant methylation is an early event in colorectal cancer (CRC pathogenesis, we hypothesised low maternal and/or post-weaning folate intake may influence methylation of genes involved in CRC development. We investigated the effects of maternal folate depletion during pregnancy and lactation on selected gene methylation in the small intestine (SI of wild type (WT and Apc+/Min mice at weaning and as adults. We also investigated the effects of folate depletion post-weaning on gene methylation in adult mice. Female C57Bl6/J mice were fed low or normal folate diets from mating with Apc+/Min males to the end of lactation. A sub set of offspring were killed at weaning. Remaining offspring were weaned on to low or normal folate diets, resulting in 4 treatment groups of Apc+/Min and WT mice. p53 was more methylated in weaning and adult WT compared with Apc+/Min mice (p>0.001. Igf2 and Apc were hypermethylated in adult Apc+/Mi n compared with WT mice (p=0.004 & p=0.012 respectively. Low maternal folate reduced p53 methylation in adults (p=0.04. Low post-weaning folate increased Apc methylation in Apc+/Min mice only (p=0.008 for interaction. These observations demonstrate that folate depletion in early life can alter epigenetic marks in a gene specific manner. Also, the differential effects of altered folate supply on DNA methylation in WT and Apc+/Min mice suggest that genotype may modulate epigenetic responses to environmental cues and may have implications for the development of personalised nutrition.

  14. The clinical value of tissue polypeptide specific antigen,neuron-specific enolase,carcinoembryonic antigen and CA125 level in small cell lung cancer%四项肿瘤标志联合检测在小细胞肺癌中的临床价值

    Institute of Scientific and Technical Information of China (English)

    李学祥; 周善良; 王慜杰; 韩彬彬; 齐军


    目的 探讨小细胞肺癌(SCLG)患者血清中组织多肽特异性抗原(TPS)、神经元特异烯醇化酶(NSE)、癌抗原125(CA125)和癌胚抗原(CEA)水平,对SCLC临床诊断、病情监测的临床意义.方法 用ELISA法检测271例SCLC和80例肺良性疾病患者及224名健康对照者血清TPS水平;同时用电化学发光法检测血清NSE、CA125和CEA水平;并用约登指数和受试者工作特征曲线(ROC曲线)分析4项肿瘤标志及其各项肿瘤标志联合检测SCLC患者的效能.结果 SCLC组的TPS、NSE、CA125和CEA血清水平明显高于肺良性疾病组和健康对照组(Z均>1.90,P均<0.01);广泛期SCLC患者的血清TPS和NSE明显高于局限期患者(Z分别为2.69、2.27,P分别为0.009、0.02).治疗后不同预后患者的TPS和NSE浓度差异有统计学意义(Z分别为4.06、3.11,P分别为0.001、0.007).多指标联合检测时,以TPS+NSE组合的敏感度最高(86.7%),其特异度、阳性预测值(PPV)和阴性预测值(NPV)分别为75.0%、81.0%和82.2%.结论 血清TPS、NSE、CA125和CEA均可作为SCLC的诊断指标,以TPS+NSE联合检测的临床价值最好.%Objective To investigate the clinical value of tissue polypeptide specific antigen(TPS),neuron-specific enolase(NSE),carcinoembryonie antigen(CEA)and CA125 in serum of small cell lung cancer(SCLC)patients and its significance in diagnosis and disease monitoring.Methods Serum leveh of TPS was detected using ELISA and serum levels of NSE,CA125 and CEA was detected using ECLin 27 1 SCLC patients.80 pulmonary benign disease patients and 224 normal healthy people.Diagnostic values of these tumor markers were analyzed by receiver operative characteristic(ROC)curve.Results The levels of TPS,NSE,CA125 and CEA iu the serum of SCLC group were signifieanfly higher than those in pulmonary benign disease and healthy group(Z>1.90,P<0.01).The levels of TPS and NSE in the serum of extensive stage small cell lung cancer(ESCLC)patients were significantly

  15. A chimeric fusion of the hASH1 and EZH2 promoters mediates high and specific reporter and suicide gene expression and cytotoxicity in small cell lung cancer cells

    DEFF Research Database (Denmark)

    Poulsen, T.T.; Pedersen, N.; Juel, H.


    Transcriptionally targeted gene therapy is a promising experimental modality for treatment of systemic malignancies such as small cell lung cancer (SCLC). We have identified the human achaete-scute homolog 1 (hASH1) and enhancer of zeste homolog 2 (EZH2) genes as highly upregulated in SCLC compar...

  16. Small Island Visitor Attractions

    Directory of Open Access Journals (Sweden)

    Haven Allahar


    Full Text Available This article proposes a process framework for developing and managing visitor attractions (VA in small island developing states with Trinidad and Tobago, a two-island state in the Caribbean, as the case study. An extensive literature review was conducted, supported by field observations, individual depth interviews, and small and large focus group meetings. The process framework identified four sets of processes: national policy formulation and legislation; inventory, classification, evaluation, and ranking of VA; general operations management involving project management activities; and site specific activities of development, operations, and maintenance. The value of the framework lies in the fact that no similar framework applicable to small islands was covered in the literature and validation was obtained from a panel of experts and a cross section of tourism stakeholders in Tobago.

  17. The specific binding to 21-nt double-stranded RNAs is crucial for the anti-silencing activity of Cucumber vein yellowing virus P1b and perturbs endogenous small RNA populations. (United States)

    Valli, Adrián; Oliveros, Juan Carlos; Molnar, Attila; Baulcombe, David; García, Juan Antonio


    RNA silencing mediated by siRNAs plays an important role as an anti-viral defense mechanism in plants and other eukaryotic organisms, which is usually counteracted by viral RNA silencing suppressors (RSSs). The ipomovirus Cucumber vein yellowing virus (CVYV) lacks the typical RSS of members of the family Potyviridae, HCPro, which is replaced by an unrelated RSS, P1b. CVYV P1b resembles potyviral HCPro in forming complexes with synthetic siRNAs in vitro. Electrophoretic mobility shift assays showed that P1b, like potyviral HCPro, interacts with double-stranded siRNAs, but is not able to bind single-stranded small RNAs or small DNAs. These assays also showed a preference of CVYV P1b for binding to 21-nt siRNAs, a feature also reported for HCPro. However, these two potyvirid RSSs differ in their requirements of 2-nucleotide (nt) 3' overhangs and 5' terminal phosphoryl groups for siRNA binding. Copurification assays confirmed in vivo P1b-siRNA interactions. We have demonstrated by deep sequencing of small RNA populations interacting in vivo with CVYV P1b that the size preference of P1b for small RNAs of 21 nt also takes place in the plant, and that expression of this RSS causes drastic changes in the endogenous small RNA populations. In addition, a site-directed mutagenesis analysis strongly supported the assumption that P1b-siRNA binding is decisive for the anti-silencing activity of P1b and localized a basic domain involved in the siRNA-binding activity of this protein.

  18. Plant Mobile Small RNAs


    Dunoyer, Patrice; Melnyk, Charles; Molnar, Attila; Slotkin, R Keith


    In plants, RNA silencing is a fundamental regulator of gene expression, heterochromatin formation, suppression of transposable elements, and defense against viruses. The sequence specificity of these processes relies on small noncoding RNA (sRNA) molecules. Although the spreading of RNA silencing across the plant has been recognized for nearly two decades, only recently have sRNAs been formally demonstrated as the mobile silencing signals. Here, we discuss the various types of mobile sRNA mol...

  19. Small Orbits

    CERN Document Server

    Borsten, L; Ferrara, S; Marrani, A; Rubens, W


    We study both the "large" and "small" U-duality charge orbits of extremal black holes appearing in D = 5 and D = 4 Maxwell-Einstein supergravity theories with symmetric scalar manifolds. We exploit a formalism based on cubic Jordan algebras and their associated Freudenthal triple systems, in order to derive the minimal charge representatives, their stabilizers and the associated "moduli spaces". After recalling N = 8 maximal supergravity, we consider N = 2 and N = 4 theories coupled to an arbitrary number of vector multiplets, as well as N = 2 magic, STU, ST^2 and T^3 models. While the STU model may be considered as part of the general N = 2 sequence, albeit with an additional triality symmetry, the ST^2 and T^3 models demand a separate treatment, since their representative Jordan algebras are Euclidean or only admit non-zero elements of rank 3, respectively. Finally, we also consider minimally coupled N = 2, matter coupled N = 3, and "pure" N = 5 theories.

  20. Propulsion Challenges for Small Spacecraft: 2005

    Institute of Scientific and Technical Information of China (English)

    Vadim Zakirov; LI Luming


    Small (<100 kg) spacecrafts are being developed in many countries but their propulsion systems still have many challenges. Although there is demand for small spacecraft propulsion, the number of missions at present is small due to several commercial and technical reasons. Poor performance of existing small spacecraft propulsion systems is one of the main reasons for the small number of missions. Several reasons are given for the poor performance of existing small spacecraft propulsion. Suggested improvements focus on small spacecraft and propulsion hardware mass optimization rather than on specific impulse enhancement. Propellantless propulsion systems are also recommended for small spacecraft interplanetary missions.

  1. Specificity of specific language impairment

    NARCIS (Netherlands)

    GoorhuisBrouwer, SM; WijnbergWilliams, BJ


    In children with specific language impairment (SLI) their problems are supposed to be specifically restricted to language. However, both on a theoretical basis as well as on a practical basis it is often difficult to make a sharp distinction between specific and nonspecific language disorders. In a

  2. Rugby-specific small-sided games training is an effective alternative to stationary cycling at reducing clinical risk factors associated with the development of type 2 diabetes: a randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Amy E Mendham

    Full Text Available The present study investigated whether rugby small-sided games (SSG could be an effective alternative to continuous stationary cycling (CYC training at reducing clinical risk factors associated with the development of type 2 diabetes mellitus (T2DM.Thirty-three middle-aged (48.6±6.6y, inactive men were randomized into a CYC (n=11, SSG (n=11, or control (CON, n=11 group. Participants trained 3d·wk(-1 for 8 weeks, while control participants maintained normal activity and dietary patterns. Exercise duration was matched between groups, which involved CYC or SSG (four quarters, interspersed with 2-min passive recovery. Both training programs were designed to induce similar internal loads of maximal heart rate (~80-85%HRmax and rating of perceived exertion. Pre- and post-intervention testing included dual-energy x-ray absorptiometry scan, graded exercise test, fasting 2 h oral glucose tolerance test and resting muscle biopsy. Western blotting was used to assess the content of skeletal muscle proteins associated with mitochondrial biogenesis and glucose regulation.Both CYC and SSG increased VO2 at 80%HRmax, and reduced glycated haemoglobin, glucose area under the curve (AUC; SSG, -2.3±2.4; CYC -2.2±1.6 mmol·L(1(120 min(1; p0.05. There were no differences within or between conditions for protein content of peroxisome proliferator-activated receptor gamma coactivator-1α, sirtuin-1, p53, glucose transporter-4, protein kinase AKT/PKB, myocyte enhancer factor 2A, mitochondrial transcription factor, nuclear respiratory factor (NRF-1, NRF-2 or mitochondrial complexes I-V (p>0.05.Rugby small-sided games is an effective alternative to continuous cycling for improving metabolic risk-factors associated with the prevention of T2DM. Despite such positive adaptations in clinical risk factors, there were no changes in the content of skeletal muscle proteins associated with glucose regulation and mitochondrial biogenesis.Australian New Zealand Clinical Trial

  3. Small Business Development Center (United States)

    Small Business Administration — Small Business Development Centers (SBDCs) provide assistance to small businesses and aspiring entrepreneurs throughout the United States and its territories. SBDCs...

  4. Plant Mobile Small RNAs (United States)

    Dunoyer, Patrice; Melnyk, Charles; Molnar, Attila; Slotkin, R. Keith


    In plants, RNA silencing is a fundamental regulator of gene expression, heterochromatin formation, suppression of transposable elements, and defense against viruses. The sequence specificity of these processes relies on small noncoding RNA (sRNA) molecules. Although the spreading of RNA silencing across the plant has been recognized for nearly two decades, only recently have sRNAs been formally demonstrated as the mobile silencing signals. Here, we discuss the various types of mobile sRNA molecules, their short- and long-range movement, and their function in recipient cells. PMID:23818501

  5. Epidermal growth factor receptor and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue-specific amino acid substitutions are associated with different histopathological prognostic factors in resected non-small-cell lung cancer. (United States)

    Seitlinger, Joseph; Renaud, Stéphane; Falcoz, Pierre-Emmanuel; Schaeffer, Mickaël; Olland, Anne; Reeb, Jérémie; Santelmo, Nicola; Legrain, Michèle; Voegeli, Anne-Claire; Weingertner, Noëlle; Chenard, Marie-Pierre; Beau-Faller, Michèle; Massard, Gilbert


    Epidermal growth factor receptor (mEGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue (mKRAS) mutations are the two main oncogenic drivers in resected non-small-cell lung cancer (NSCLC). We aimed to evaluate the correlation between histopathological prognostic factors and these mutations in resected NSCLC. We retrospectively reviewed data from 841 patients who underwent a surgical resection with a curative intent for NSCLC between 2007 and 2012. KRAS mutations were observed in 255 patients (32%) and mEGFR in 103 patients (12%). A correlation was observed between mKRAS patients and lymph node involvement [Cramer's V: 0.451, P V: 0.235, P = 0.02, OR: 3.04 (95% CI: 1.5-6.3), P = 0.004]. High lymph node ratio and angioinvasion were also significantly more frequent in mKRAS [Cramer's V: 0.373, P V: 0.269, P V: 0.459, P V: 0.45, P < 0.001 OR: 21.14 (95% CI: 9.2-48.3), P < 0.001, respectively]. We observed a correlation between mKRAS and negative histopathological prognostic factors and between mEGFR and positive prognostic factors. One can wonder whether histopathological prognostic factors are only clinical reflections of molecular alterations. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. A double blind, randomized, placebo controlled trial of the efficacy, quality of life and safety of food allergen-specific sublingual immunotherapy in client owned dogs with adverse food reactions: a small pilot study. (United States)

    Maina, Elisa; Cox, Eric


    Food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a novel and successful approach for desensitizing human patients to specific food allergens. It has not been tested in dogs. To investigate the efficacy, quality of life (QoL), tolerability and safety of FA-SLIT in dogs with adverse food reactions (AFR). Dogs with proven AFR were randomized to treatment (T group; n = 7) or placebo (P group; n = 6) to receive either FA-SLIT (based on the results of a food elimination trial) or glycerinated saline, respectively. The treatment was continued daily for 6 months with fortnightly dosage escalations. To evaluate the treatment, pruritus Visual Analog Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), QoL, faecal consistency scores, owner assessment, overall tolerability scores and blood analyses were assessed. Eleven dogs completed the study, two dogs in the T group were withdrawn by the owner after FA-SLIT exacerbated clinical signs of AFR. Statistical tests showed significant protection against food challenge induced clinical signs following FA-SLIT therapy, as indicated by reduced pVAS and CADESI scores (P < 0.05). The QoL did not differ between groups. The treatment was rated as effective or quite effective by 80% of the owners, whereas placebo was rated as ineffective by all owners. FA-SLIT was effective, well tolerated and safe. No severe adverse events were recorded; erythema and pruritus were reported in association with only 0.7% of the dispensed doses. Larger clinical trials with more extended maintenance immunotherapy periods will be needed to provide more precise estimates of efficacy and frequency of adverse events. © 2016 ESVD and ACVD.

  7. Gender-Specific Health Challenges Facing Women (United States)

    ... with twitter share with linkedin Gender-Specific Health Challenges Facing Women Global Research Global Research NIAID's Role ... Career Stage Postdocs' Guide to Gaining Independence Small Business Programs Compare NIAID’s Small Business Programs High-Priority ...

  8. Specific Dyslexia. (United States)

    Naidoo, Sandhya

    The investigation reported in this volume attempts to clarify some issues relating to the existence, nature, and causes of specific dyslexia. Based on an extended study of 98 boys of at least average intelligence with severe reading and spelling problems, the report provides detailed data relating to their developmental and perinatal histories,…

  9. Are Subject Small Clauses Really Small Clauses? (United States)

    Kubo, Miori


    This paper discusses the ongoing debate over small clauses concerning the structure of the verb phrase in "I consider Bill smart." It is demonstrated that the subject constituent in question is not a small clause, but a Noun Phrase (NP), following Noun (N). It is shown that some peculiar phenomena under the small clause analysis are natural…

  10. Application of serum levels of pro-gastrin releasing peptide, tissue polypeptide specific antigen and neuron specific enolase in therapy monitoring in small cell lung cancer patients%血清ProGRP、TPS及NSE在小细胞肺癌患者治疗监测中的应用

    Institute of Scientific and Technical Information of China (English)

    王慜杰; 李学祥; 高佳; 韩彬彬; 付超; 王景智; 张春; 齐军


    Objective To evaluate the clinical significance of serum levels of ProGRP, TPS and NSE in diagnosis and therapy monitoring in small cell lung cancer patients. Methods The levels of serum ProGRP, TPS and NSE in 51 SCLC patients (SCLC group), 60 benign pulmonary disease patients (benign disease group ) and 60 healthy people (healthy group ) were determined using chemiluminescent immunoassay, ELISA and electrochemiluminescent immunoassay respectively. Blood samples were collected and detected prior to therapy, before the second course of chemotherapy and the third course of chemotherapy consecutively in all the 51 SCLC patients. Results The serum ProGRP, TPS and NSE concentrations prior to chemotherapy in limited stage SCLC (LSCLC) were 136. 9(22.8-631.7)ng/L, 78. 2(56.4-114.6) U/L and 28.1(20.9-46.1)μg/L, respectively; And in extensive stage SCLC patients (ESCLC) were 1 106.6(41.2-2161.1) ng/L, 230. 9( 143.5-259.0) U/L and 81.1 (34.3-140.0)μg/L, respectively. The serum concentrations of the 3 markers in benign disease group were 19. 7 ( 9. 5-29. 1 )ng/L, 48. 7 ( 17.9-95.4) U/L and 12. 1(1.2-13.9) μg/L; and in healthy group were 20.3(10.7-30.6) ng/L, 50.3(19.5-70.7) U/L and 11.7 (1.1-13.4)μg/L, respectively. The Kruskal-Wallis test showed significantly statistical difference in different groups of the 3 tumor markers, Chi-Square were 51. 368,36. 532 and 81. 645( P <0. 01 ). Significant statistically differences showed when the concentrations of the 3 marks of the 2 control group were compared with that of the LSCLC group ( U =491, 827, 609 and 476, 831, 585,respectively, P < 0. 05 ). Differences were also statistically significant when the 2 control group compared with that of the ESCLC group ( U = 314,532,456 and 302,553,430, respectively, P < 0. 01 ). The AUC of ProGRP was 0.832 +0.029(95% CI:0.774-0.890). When cutoff value of ProGRP set as 37.7 ng/L, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and Youden

  11. HRT Specification

    CERN Document Server

    Möller, M


    In the context of the AIS Project (Advanced Informatics Systems for administration and management) a study has been conducted that resulted in the definition of a high level information systems model. Thirteen proposed systems were defined for detailed analysis. The Finance, Foundation, Human Resources, Logistics and Purchasing areas have been studied in detail. These studies have lead to the purchase and implementation of the ORIAC and SIRIAC packages, the Foundation database, the Oracle HR package, the Triton package and EDH and BHT. This specification describes the Human Resources Toolkit (HRT) intended to be used for accessing data in the HR and Foundation systems. This toolkit should help the divisions carry out their Human Resource management, planning and follow-up. It will have extensive report generation capabilities and offer a variety of standard graphs. It should have an easy-to-use graphical user interface and run on the CERN standard desktop platforms.

  12. Small satellites and their regulation

    CERN Document Server

    Jakhu, Ram S


    Since the launch of UoSat-1 of the University of Surrey (United Kingdom) in 1981, small satellites proved regularly to be useful, beneficial, and cost-effective tools. Typical tasks cover education and workforce development, technology demonstration, verification and validation, scientific and engineering research as well as commercial applications. Today the launch masses range over almost three orders of magnitude starting at less than a kilogram up to a few hundred kilograms, with budgets of less than US$ 100.00 and up to millions within very short timeframes of sometimes less than two years. Therefore each category of small satellites provides specific challenges in design, development and operations. Small satellites offer great potentials to gain responsive, low-cost access to space within a short timeframe for institutions, companies, regions and countries beyond the traditional big players in the space arena. For these reasons (particularly the low cost of construction, launch and operation), small (m...

  13. Cryoablation for Small Renal Masses

    Directory of Open Access Journals (Sweden)

    J. L. Dominguez-Escrig


    Full Text Available Advances in imaging techniques (CT and MRI and widespread use of imaging especially ultrasound scanning have resulted in a dramatic increase in the detection of small renal masses. While open partial nephrectomy is still the reference standard for the management of these small renal masses, its associated morbidity has encouraged clinicians to exploit the advancements in minimally invasive ablative techniques. The last decade has seen the rapid development of laparoscopic partial nephrectomy and novel ablative techniques such as, radiofrequency ablation (RFA, high-intensity focused ultrasound (HIFU, and cryoablation (CA. In particular, CA for small renal masses has gained popularity as it combines nephron-sparing surgery with a minimally invasive approach. Studies with up to 5-year followup have shown an overall and cancer-specific 5-year survival of 82% and 100%, respectively. This manuscript will focus on the principles and clinical applications of cryoablation of small renal masses, with detailed review of relevant literature.

  14. Lung cancer - small cell (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  15. Small Business Size Standards (United States)

    Small Business Administration — Certain government programs, such as SBA loan programs and contracting opportunities, are reserved for small business concerns. In order to qualify, businesses must...

  16. Specific phobias. (United States)

    Hamm, Alfons O


    Exposure based treatments in which patients are systematically confronted with their feared objects of situations are highly effective in the treatment of specific phobias and produce stable improvement both in reported fear and behavioral avoidance. Exposure in reality is more effective in most cases than exposure in sensu. For situations that are difficult to realize, exposure in virtual environments has become increasingly valuable. Exposure in vivo is clearly superior to pharmacotherapy, although cognitive enhancers have been successfully used recently to increase the effect of exposure therapy. The induction of relaxation is not a necessary precondition for exposure therapy. Rather the current mechanisms of change focus on extinction learning as being the central mechanism both on a cognitive level namely that the feared object is no longer associated with severely threatening consequence but also on an affective level, meaning that feared cue is no longer capable to activate the fear circuit in the brain. Accordingly future diagnostic categorizations of phobic disorders in the DSM-V should rather focus on the pattern of the fear response that needs to be changed than on the eliciting cues or situations that are avoided.

  17. Thinking Big about Getting Small: An Ideological Genealogy of Small-School Reform (United States)

    Kafka, Judith


    Background: Support for small schools, and specifically for the creation of small, autonomous schools of choice, has grown considerably in the past decade--particularly in the context of urban schooling. Funded by private and public monies, small-school initiatives have been implemented in most of the nation's city school districts and have become…

  18. Chartering Launchers for Small Satellites (United States)

    Hernandez, Daniel

    The question of how to launch small satellites has been solved over the years by the larger launchers offering small satellites the possibility of piggy-backing. Specific fixtures have been developed and commercialized: Arianespace developed the ASAP interface, the USAF studied ESPA, NASA has promoted Shuttle launch possibilities, Russian authorities and companies have been able to find solutions with many different launchers... It is fair to say that most launcher suppliers have worked hard and finally often been able to find solutions to launch most small satellites into orbit. It is also true, however, that most of these small satellites were technology demonstration missions capable of accepting a wide range of orbit and launch characteristics: orbit altitude and inclination, launch date, etc. In some cases the small satellite missions required a well-defined type of orbit and have therefore been obliged to hire a small launcher on which they were the prime passenger. In our paper we would like to propose an additional solution to all these possibilities: launchers could plan well in advance (for example about 3 years), trips to precisely defined orbits to allow potential passengers to organize themselves and be ready on the D-Day. On the scheduled date the chartered launcher goes to the stated orbit while on another date, another chartered launcher goes to another orbit. The idea is to organize departures for space like trains or airplanes leaving on known schedules for known destinations.

  19. "small ACCELERATORS" 24 May - 2 June 2005

    CERN Multimedia


    CERN Accelerator School and Kernfysisch Versneller Instituut (KVI) Groningen, the Netherlands announce a course on "Small Accelerators", Hotel Golden Tulip Drenthe, Zeegse, the Netherlands, 24 May - 2 June 2005. This specialised course is dedicated to the physics and the main applications of small accelerators. The course will review the different accelerator types as well as their specificities in terms of accelerator physics.


    Directory of Open Access Journals (Sweden)

    Mihai Răzvan Constantin BARBU


    Full Text Available In this paper we analyzed the branding in small business. Using a desk research on Internet and the press we have identified the practices small businesses use to enhance their brand and the brand dynamics in small business. Our main contribution is that we tried to figure out the strategy of branding in small business. This need further to be investigated in order to understand how branding works in small business and to better capture the role of branding in small business.

  1. Small angle neutron scattering

    Directory of Open Access Journals (Sweden)

    Cousin Fabrice


    Full Text Available Small Angle Neutron Scattering (SANS is a technique that enables to probe the 3-D structure of materials on a typical size range lying from ∼ 1 nm up to ∼ a few 100 nm, the obtained information being statistically averaged on a sample whose volume is ∼ 1 cm3. This very rich technique enables to make a full structural characterization of a given object of nanometric dimensions (radius of gyration, shape, volume or mass, fractal dimension, specific area… through the determination of the form factor as well as the determination of the way objects are organized within in a continuous media, and therefore to describe interactions between them, through the determination of the structure factor. The specific properties of neutrons (possibility of tuning the scattering intensity by using the isotopic substitution, sensitivity to magnetism, negligible absorption, low energy of the incident neutrons make it particularly interesting in the fields of soft matter, biophysics, magnetic materials and metallurgy. In particular, the contrast variation methods allow to extract some informations that cannot be obtained by any other experimental techniques. This course is divided in two parts. The first one is devoted to the description of the principle of SANS: basics (formalism, coherent scattering/incoherent scattering, notion of elementary scatterer, form factor analysis (I(q→0, Guinier regime, intermediate regime, Porod regime, polydisperse system, structure factor analysis (2nd Virial coefficient, integral equations, characterization of aggregates, and contrast variation methods (how to create contrast in an homogeneous system, matching in ternary systems, extrapolation to zero concentration, Zero Averaged Contrast. It is illustrated by some representative examples. The second one describes the experimental aspects of SANS to guide user in its future experiments: description of SANS spectrometer, resolution of the spectrometer, optimization of

  2. Small-scale Biorefining

    NARCIS (Netherlands)

    Visser, de C.L.M.; Ree, van R.


    One promising way to accelerate the market implementation of integrated biorefineries is to promote small (regional) biorefinery initiatives. Small-scale biorefineries require relatively low initial investments, and therefore are often lacking the financing problems that larger facilities face. They

  3. Chairing a Small Department. (United States)

    Bowker, Lee H.; Lynch, David M.

    Ten management problems for chairs of small departments in small colleges are discussed, along with problem-solving strategies for these administrators. Serious disagreements within a small and intimate department may create a country club culture in which differences are smoothed over and the personal idiosyncrasies of individual members are…

  4. Small Stirling Cycle Convertors (United States)

    Penswick, L. Barry; Schreiber, Jeffery


    The Stirling convertor concept continues to be a viable potential candidate for various space power applications at electrical power levels ranging from greater than 100 KW to on the order of 10+watts. Various development efforts, both in the past and currently underway, have clearly demonstrated the potential for long operating life of this concept, its high efficiency in comparison to alternative power systems (>50% of Carnot based on electric power out to heat in), and its excellent specific power characteristics. A truly unique attribute of the Stirling convertor is the ability to maintain many of these same advantages at significantly lower electrical power levels (on the order of 1 watt and below). This provides the opportunity for a wider range of potential space power applications and the use of alternative heat sources operating at dramatically lower hot-end temperatures (about 250 °C vs. current values of about 650 °C). An overview of low-power Stirling convertors and related Stirling cooler technology is provided with an emphasis on assessing the technical maturity of this concept's key components at the low power level of interest. A conceptual design of a small, 1-watt (electrical output) Stirling convertor utilizing multiple Low Weight Radioisotope Heater Unit heat sources will be described. Key technical issues in the development of this power level Stirling convertor are discussed.

  5. How Small are Small Stars Really? (United States)


    VLT Interferometer Measures the Size of Proxima Centauri and Other Nearby Stars [1] Summary At a distance of only 4.2 light-years, Proxima Centauri is the nearest star to the Sun currently known [2]. It is visible as an 11-magnitude object in the southern constellation of Centaurus and is the faintest member of a triple system, together with Alpha Centauri , the brightest (double) star in this constellation. Proxima Centauri is a very-low-mass star, in fact barely massive enough to burn hydrogen to helium in its interior. It is about seven times smaller than the Sun, and the surface temperature is "only" about 3000 degrees, about half of that of our own star. Consequently, it is also much fainter - the intrinsic brightness is only 1/150th of that of our Sun. Low-mass stars are very interesting objects , also because the physical conditions in their interiors have much in common with those of giant planets, like Jupiter in our solar system. A determination of the sizes of the smallest stars has been impossible until now because of their general faintness and lack of adequate instrumentation. However, astronomers have long been keen to move forward in this direction, since such measurements would provide indirect, crucial information about the behaviour of matter under extreme conditions. When the first observations with the VLT Interferometer (VLTI), combining the light from two of the 8.2-m VLT Unit Telescopes (ANTU and MELIPAL), were made one year ago ( ESO PR 23/01 ), interferometric measurements were also obtained of Proxima Centauri . They formed part of the VLTI commissioning and the data were soon released to the ESO community, cf. the special website. Now, an international team of astronomers from Switzerland, France and ESO/Chile has successfully analysed these observations by means of newly developed, advanced software. For the first time ever, they obtained a highly accurate measurement of the size of such a small star . Three other small stars were also

  6. Small cell glioblastoma or small cell carcinoma

    DEFF Research Database (Denmark)

    Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H


    was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

  7. Clinical Significance of Detection of Serum Values of Neuron Specific Enolase Before and After Treatment for Small Cell Lung Cancer%小细胞肺癌患者治疗前后血清NSE测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    薛峰; 王莉彦; 张明岩; 蔡莉


    Background and objective It has been proven that neuron specific enolase (NSE) was one of the sensitive tumor markers for small cell lung cancer (SCLC). The aim of this study is to investigate the usefulness of serum NSE values as diagnostic and prognostic factors in patients with SCLC. Methods Serum NSE was detected by electrochemiluminescence method In 57 SCLC cases pre- and post treatment. Survival curves were constructed using the Kaplan-Meier method and then compared using the Log-rank test. Results Pre-treatment serum NSE values are prognostic factors for overall survival of patients with SCLC. There was a statistically significant difference In the pretreatment NSE levels of patients who were at an extensive stage compared with the values of those patients who were at a limited stage (P<0.00l). The rate of change between the pre- and post-treatment serum NSE levels was not related to the overall survival (P=0.084). Conclusion NSE Is an Ideal tumor marker for the diagnosis and assessment prognosis of SCLC.%背景与目的,神经烯醇化酶(neuron specific enolase,NSE)是小细胞肺癌(small cell lung cancer,SCLC)敏感的肿瘤标记物之一.本研究旨在研究血清NSE水平作为SCLC诊断和预后因索的实用性.方法,治疗前后应用电化学发光法测定57例SCLC患者的血清NSE.应用Kaplan-Meier法构建生存曲线,采用对数秩检验法(Log-rank)进行曲线之间的比较.结果,SCLC患者治疗前血清NSE水平是患者总生存期的预后因素,广泛期患者与局限期患者的治疗前血清NSE水平有统计学差异(P<0.001),治疗前后NSE的变化率与总生存期无关(P=0.084).结论,NSE是SCLC患者诊断和评估预后的理想肿瘤标记物.

  8. Small asteroid system evolution


    Jacobson, Seth A.


    Observations with radar, photometric and direct imaging techniques have discovered that multiple asteroid systems can be divided clearly into a handful of different morphologies, and recently, the discovery of small unbound asteroid systems called asteroid pairs have revolutionized the study of small asteroid systems. Simultaneously, new theoretical advances have demonstrated that solar radiation dictates the evolution of small asteroids with strong implications for asteroid internal structur...

  9. Small asteroid system evolution


    Jacobson, Seth A.


    Observations with radar, photometric and direct imaging techniques have discovered that multiple asteroid systems can be divided clearly into a handful of different morphologies, and recently, the discovery of small unbound asteroid systems called asteroid pairs have revolutionized the study of small asteroid systems. Simultaneously, new theoretical advances have demonstrated that solar radiation dictates the evolution of small asteroids with strong implications for asteroid internal structur...

  10. Sonography of the small intestine

    Institute of Scientific and Technical Information of China (English)

    Kim Nylund; Svein (φ)degaard; Trygve Hausken; Geir Folvik; Gülen Arslan Lied; Ivan Viola; Helwig Hauser; Odd-Helge Gilja


    In the last two decades, there has been substantial development in the diagnostic possibilities for examining the small intestine. Compared with computerized tomography, magnetic resonance imaging, capsule endoscopy and double-balloon endoscopy, ultrasonography has the advantage of being cheap, portable, flexible and user- and patient-friendly, while at the same time providing the clinician with image data of high temporal and spatial resolution. The method has limitations with penetration in obesity and with intestinal air impairing image quality. The flexibility ultrasonography offers the examiner also implies that a systematic approach during scanning is needed. This paper reviews the basic scanning techniques and new modalities such as contrast-enhanced ultrasound, elastography, strain rate imaging, hydrosonography, allergosonography, endoscopic sonography and nutritional imaging, and the literature on disease-specific findings in the small intestine. Some of these methods have shown clinical benefit, while others are under research and development to establish their role in the diagnostic repertoire. However, along with improved overall image quality of new ultrasound scanners, these methods have enabled more anatomical and physiological changes in the small intestine to be observed. Accordingly, ultrasound of the small intestine is an attractive clinical tool to study patients with a range of diseases.

  11. Small Intestine Disorders (United States)

    ... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.


    Directory of Open Access Journals (Sweden)

    Slobodan Ivanovic


    Full Text Available After introductory explanations regarding the selection problems of small enterprises in the Croatian hotel industry, the author provides a number of key indicators of their role in improving the competitiveness of the Croatian hotel industry in the global tourism market. In developed tourism countries, small enterprises have a dominant share in the structure of the hotel industry, and their importance is growing even in the former socialist countries of Europe. Small hotels in Italy accounted for more than 50%, and in Austria with more than 70% of lodging facilities and represent a generator of hotel business in a large number of European tourism countries, and great attention is given to the small enterpreneurs stimulating their growth with different measures of tourist and general economy politics. The author reflects on the Croatian experience of the small businesses in the hospitality through research of development of small family hotels and their importance for the improvement of the supply of the Croatian hotel industry which future is built on personal approach to guests and present trends in the tourism market. States that the role of the National Association of family and small hotels, which represents the specific interests of small hoteliers and enables the continuous improvement of the quality of their offerings, as well as measures to encourage small business development at the macro level. Based on the made analysis the measures of increasing the efficiency of small businesses in the Croatian hospitality are given.

  13. Small Animal Care. (United States)

    Livesey, Dennis W.; Fong, Stephen

    This small animal care course guide is designed for students who will be seeking employment in veterinary hospitals, kennels, grooming shops, pet shops, and small-animal laboratories. The guide begins with an introductory section that gives the educational philosophy of the course, job categories and opportunities, units of instruction required…

  14. Small Schools, Big Future (United States)

    Halsey, R. John


    Historically, small schools have played a very important role in the provision of schooling in Australia. Numerically, using an enrollment of 200 or less, small schools represent approximately 45% of the schools in Australia. Population growth and the consequences of this, in particular for food production, water and energy, mean that the…

  15. Hume = Small Hume


    Ketland, Jeffrey


    We can modify Hume’s Principle in the same manner that George Boolos suggested for modifying Frege’s Basic Law V. This leads to the principle Small Hume. Then, we can show that Small Hume is interderivable with Hume’s Principle.

  16. Small School Reform

    Directory of Open Access Journals (Sweden)

    Carroll E. Bronson


    Full Text Available This qualitative ethnographic case study explored the evolution of a public urban high school in its 3rd year of small school reform. The study focused on how the high school proceeded from its initial concept, moving to a small school program, and emerging as a new small high school. Data collection included interviews, observations, and document review to develop a case study of one small high school sharing a multiplex building. The first key finding, “Too Many Pieces, Not Enough Glue,” revealed that the school had too many new programs starting at once and they lacked a clear understanding of their concept and vision for their new small school, training on the Montessori philosophies, teaching and learning in small schools, and how to operate within a teacher-cooperative model. The second key finding, “A Continuous Struggle,” revealed that the shared building space presented problems for teachers and students. District policies remain unchanged, resulting in staff and students resorting to activist approaches to get things done. These findings offer small school reform leaders suggestions for developing and sustaining a small school culture and cohesion despite the pressures to revert back to top-down, comprehensive high school norms.

  17. IBM Small Business Survey. (United States)

    International Business Machines Corp., Armonk, NY.

    A telephone survey conducted March 15-22, 1991, examined how small businesses are currently performing. Interviewees were 400 small business owners randomly selected from a Dun and Bradstreet list of companies with 50 or fewer employees. Major findings were as follows: (1) owners were survivors, highly confident in their own abilities, and…

  18. Small Wind Information (Postcard)

    Energy Technology Data Exchange (ETDEWEB)


    The U.S. Department of Energy's Wind Powering America initiative maintains a website section devoted to information about small wind turbines for homeowners, ranchers, and small businesses. This postcard is a marketing piece that stakeholders can provide to interested parties; it will guide them to this online resource.

  19. Small business & employment

    NARCIS (Netherlands)

    Lieshout, Harm van


    Understanding SMEs is essential to our aspired succes as an economic partner. Small enterprises are not small big enterprises, and differ substantially among them The key ingredient to our help from education remains the education of a new highly skilled generation of workers … and entrepreneurs.

  20. Small Group Inquiry. (United States)

    Koller, Martin M.

    Learning in small groups is a practical way to bring about behavior change. The inquiry learning process is perceived to be the most natural and scientific way of learning. Skills developed include those of problem-solving task analysis, decision-making, value formation and adaptability. The art of small group interaction is developed. Factual…

  1. Small GTPases and cilia. (United States)

    Li, Yujie; Hu, Jinghua


    Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane- and cytoskeleton-related cellular processes. Recently, mounting evidences have highlighted the role of various small GTPases, including the members in Arf/Arl, Rab, and Ran subfamilies, in cilia formation and function. Once overlooked as an evolutionary vestige, the primary cilium has attracted more and more attention in last decade because of its role in sensing various extracellular signals and the association between cilia dysfunction and a wide spectrum of human diseases, now called ciliopathies. Here we review recent advances about the function of small GTPases in the context of cilia, and the correlation between the functional impairment of small GTPases and ciliopathies. Understanding of these cellular processes is of fundamental importance for broadening our view of cilia development and function in normal and pathological states and for providing valuable insights into the role of various small GTPases in disease processes, and their potential as therapeutic targets.


    Directory of Open Access Journals (Sweden)

    Pavel Skopec


    Full Text Available This paper deals with determining the specific emissions from the combustion of two kinds of biomass fuels in a small-scale boiler. The tested fuels were pellets made of wood and pellets made of rape plant straw. In order to evaluate the specific emissions, several combustion experiments were carried out using a commercial 25 kW pellet-fired boiler. The specific emissions of CO, SO2 and NOx were evaluated in relation to a unit of burned fuel, a unit of calorific value and a unit of produced heat. The specific emissions were compared with some data acquired from the reference literature, with relatively different results. The differences depend mainly on the procedure used for determining the values, and references provide no information about this. Although some of our experimental results may fit with one of the reference sources, they do not fit with the other. The reliability of the references is therefore disputable.

  3. SmallSat Database (United States)

    Petropulos, Dolores; Bittner, David; Murawski, Robert; Golden, Bert


    The SmallSat has an unrealized potential in both the private industry and in the federal government. Currently over 70 companies, 50 universities and 17 governmental agencies are involved in SmallSat research and development. In 1994, the U.S. Army Missile and Defense mapped the moon using smallSat imagery. Since then Smart Phones have introduced this imagery to the people of the world as diverse industries watched this trend. The deployment cost of smallSats is also greatly reduced compared to traditional satellites due to the fact that multiple units can be deployed in a single mission. Imaging payloads have become more sophisticated, smaller and lighter. In addition, the growth of small technology obtained from private industries has led to the more widespread use of smallSats. This includes greater revisit rates in imagery, significantly lower costs, the ability to update technology more frequently and the ability to decrease vulnerability of enemy attacks. The popularity of smallSats show a changing mentality in this fast paced world of tomorrow. What impact has this created on the NASA communication networks now and in future years? In this project, we are developing the SmallSat Relational Database which can support a simulation of smallSats within the NASA SCaN Compatability Environment for Networks and Integrated Communications (SCENIC) Modeling and Simulation Lab. The NASA Space Communications and Networks (SCaN) Program can use this modeling to project required network support needs in the next 10 to 15 years. The SmallSat Rational Database could model smallSats just as the other SCaN databases model the more traditional larger satellites, with a few exceptions. One being that the smallSat Database is designed to be built-to-order. The SmallSat database holds various hardware configurations that can be used to model a smallSat. It will require significant effort to develop as the research material can only be populated by hand to obtain the unique data

  4. Rapid Response Small Machining NNR Project 703025

    Energy Technology Data Exchange (ETDEWEB)

    Kanies, Tim


    This project was an effort to develop a machining area for small sized parts that is capable of delivering product with a quick response time. This entailed focusing efforts on leaning out specific work cells that would result in overall improvement to the entire machining area. This effort involved securing the most efficient available technologies for these areas. In the end, this incorporated preparing the small machining area for transformation to a new facility.

  5. Small Vehicle Launch Platform (United States)


    the art will appreciate that release 21 mechanisms 41 can be a spring-loaded release pin with a lanyard 22 pull initiated by an actuator mechanism explosive squib 23 which breaks the attachment latching on the small UUV. Whatever 1 release mechanism is used, it is controlled by the host...carries four small 1 UUV’s, it will be understood that, depending on the size of the 3 small UUV’s employed, greater or fewer numbers of UUV’s can be 4

  6. Small scale optics

    CERN Document Server

    Yupapin, Preecha


    The behavior of light in small scale optics or nano/micro optical devices has shown promising results, which can be used for basic and applied research, especially in nanoelectronics. Small Scale Optics presents the use of optical nonlinear behaviors for spins, antennae, and whispering gallery modes within micro/nano devices and circuits, which can be used in many applications. This book proposes a new design for a small scale optical device-a microring resonator device. Most chapters are based on the proposed device, which uses a configuration know as a PANDA ring resonator. Analytical and nu

  7. Myositis specific autoantibodies : specificity and clinical applications

    NARCIS (Netherlands)

    Hengstman, G.J.D.


    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as compar

  8. Myositis specific autoantibodies : specificity and clinical applications

    NARCIS (Netherlands)

    Hengstman, G.J.D.


    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as compar

  9. Adult Education in Small States: The Case of Malta (United States)

    Mayo, Peter; Pace, Paul J.; Zammit, Edward


    A small state faces several challenges with regard to adult continuing education and training. The paper discusses some of these challenges with specific reference to the Mediterranean small island state of Malta. It starts with a general discussion of some of the issues affecting adult education in a small state such as Malta that paves the way…

  10. When Fewer Is More: Small Groups in Early Childhood Classrooms (United States)

    Wasik, Barbara


    Small group instruction is important yet it is one of the most underused strategies in early childhood classrooms. This paper presents guidelines based on research-based best practices for using small groups in early childhood. In addition, the benefits of small group instruction for both children and teachers are described. Specific suggestions…

  11. Small Intestine Cancer Treatment (United States)

    ... intestine . The digestive system removes and processes nutrients ( vitamins , minerals , carbohydrates , fats, proteins , and water) from foods ... a microscope to see whether they contain cancer. Bypass : Surgery to allow food in the small intestine ...

  12. Small Mammal Trapping 2003 (United States)

    US Fish and Wildlife Service, Department of the Interior — Small mammal traps were placed in the Baring division and in the Edmunds division of Moosehom National Wildlife Refuge. There were a total of 98 traps set for up to...

  13. Small bowel bacterial overgrowth (United States)

    ... Surgical procedures that create a loop of small intestine where excess bacteria can grow. An example is a Billroth II type of stomach removal ( gastrectomy ). Some cases of irritable bowel syndrome (IBS).

  14. Small public private partnerships

    DEFF Research Database (Denmark)

    Koch, Christian; Jensen, Jesper Ole


    by the authorities, which recommend sizes over 13,5 million € (100 million DKr). PPP is here understood as Design, Build, Finance and Operate projects. The paper shows, when looking at Germany, Italy and United Kingdom, that small PPP (below 13,5 million €) are widespread in two investigated countries; United...... Kingdom and Italy, whereas German projects are still emerging. Quantitative material on small PPP in Italy and UK shows no lower limit in size for these established PPPs. This apparent paradox is then qualitatively investigated. Only small projects are investigated, and these seem largely to be sound...... businesses and represent operable units for the clients and citizens. Cases are focused within education and healthcare. The analysis suggests that another type of economy apparently is in play. It is thus characteristic within education projects in UK that the largest portion of small PPPs are of a size...

  15. Small intestine (image) (United States)

    The small intestine is the portion of the digestive system most responsible for absorption of nutrients from food into the bloodstream. The pyloric sphincter governs the passage of partly digested food ...

  16. Impact on Small Mammals

    African Journals Online (AJOL)

    abundance and diversity of the small mammal community on burnt and unbumt habitats of the area using .... Captured animals were shaken gently ..... Wetlands Management Project: Environ- ... ofrodents, SwedishNatural Science Research.

  17. Small Satellite Transporter Project (United States)

    National Aeronautics and Space Administration — The primary objective is to determine whether this small satellite transporter is capable of transporting at least four 6U CubeSats is possible for a given set of...

  18. Diagnostic value of pro-gastrin-releasing peptide and neuron-specific enolase for small cell lung cancer%胃泌素释放肽前体和神经元特异性烯醇化酶对小细胞肺癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    朱金秀; 谢强; 钟爱虹; 卢筠; 廖胜祥; 臧焕平; 上官昌吉; 林清华


    目的:探讨血清肿瘤标志物———胃泌素释放肽前体(ProGRP)和神经特异性烯醇化酶(NSE)对小细胞肺癌(SCLC)的诊断价值。方法检测2014年6月至2015年7月该院收治的134例经病理检查确诊为SCLC患者(SCLC组)、126例非小细胞肺癌(NSCLC)患者(NSCLC组)、72例肺炎患者(肺炎组)、52例肺结核患者(肺结核组)血清ProGRP及NSE水平,应用SAS9.0统计软件进行数据分析,组间比较采用Kruskal-Wallis H检验和Nemenyi法检验。结果 SCLC组患者血清ProGRP、NSE水平均明显高于NSCLC组、肺炎组、肺结核组,差异均有统计学意义(P<0.01)。检测ProGRP、NSE诊断SCLC的灵敏度分别为83.6%、91.0%,特异性分别为94.3、76.9%。二者联合检测诊断SCLC的灵敏度可提高至98.5%。结论检测肿瘤标志物———ProGRP、NSE在SCLC的诊断中具有很重要的临床意义。%Objective To evaluate the diagnostic values of pro-gastrin-releasing peptide (ProGRP)and neuron specific enolase(NSE)for small cell lung cancer(SCLC). Methods Serum ProGRP and NSE levels were detected in our hospital from June 2014 to July 2015 in 134 cases of pathologically diagnosed SCLC(SCLC group),126 cases of non small cell lung cancer (NSCLC group),72 cases of pneumonia(pneumonia group) and 54 cases of pulmonary TB. The obtained data were analyzed by using the SAS9.0 software. The inter-group comparison adopted Kruskal-Wallis H test and Nemenyi test. Results The levels of serum Pro-GRP and NSE in the SCLC group were significant higher than those in the NSCLC group ,pneumonia group and pul monary TB group,the difference was statistically significant(P<0.01). The sensitivities of detecting ProGRP and NSE for diagnosing SCLC of were 83.5%and 91.0%respectively ,the specificities were 94.3%and 76.9%respectively. The sensitivity of their com-bined detection could increase to 98.5%. Conclusion Detecting tumor marker ProGRP and NSE has a very

  19. Small simple impact craters

    CERN Document Server

    Sparavigna, Amelia Carolina


    The paper discusses some examples of image processing applied to improve optical satellite imagery of small craters (Kamil, Veevers, Haviland). The examples show that image processing can be quite useful for further in-situ researches, because the resultant imagery helps to have a better picture of the crater shape and of the distribution of debris about it. The paper is also disclosing an interesting underwater structure, with shape and size of a small crater, located on the coast-line of Sudan.

  20. Small test SDHW systems

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian


    Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

  1. Neptune's small satellites (United States)

    Thomas, P.


    The small satellites of Neptune and other planets discovered during the Voyager 2 mission are discussed in terms of their composition and relationship to the planetary systems. The satellite Proteus is described in terms of its orbit, five other satellites are described, and they are compared to ther small satellites and systems. Neptune's satellites are hypothesized to be related to the ring system, and the satellite Galatea is related to the confinement of the rings.

  2. Small business & employment


    Lieshout, Harm van


    Understanding SMEs is essential to our aspired succes as an economic partner. Small enterprises are not small big enterprises, and differ substantially among them The key ingredient to our help from education remains the education of a new highly skilled generation of workers … and entrepreneurs. Entrepreneurs do not necessarily want to be employers, and are not necessarily good at it. But to ensure a healthy life in a healthy business, they need to be.

  3. Small test SDHW systems

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian


    Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

  4. Small-x physics

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, A.H. [Columbia Univ., New York, NY (United States). Dept. of Physics


    After a brief review of the kinematics of deep inelastic lepton-proton scattering, the parton model is described. Small-x behavior coming from DGLAP evolution and from BFKL evolution is discussed, and the two types of evolution are contrasted and compared. Then a more detailed discussion of BFKL dynamics is given. The phenomenology of small-x physics is discussed with an emphasis on ways in which BFKL dynamics may be discussed and measured. 45 refs., 12 figs.


    Institute of Scientific and Technical Information of China (English)

    D. Ditschke; O. Gothel; H. Weilbeer


    Long term morphological simulations using complete coupled models lead to very time consuming computations. Latteux (1995) presented modelling techniques developed for tidal current situations in order to reduce the computational effort. In this paper the applicability of such methods to small scale problems is investigated. It is pointed out that these methods can be transferred to small scale problems using the periodicity of the vortex shedding process.

  6. How small is a small cloud?

    Directory of Open Access Journals (Sweden)

    I. Koren


    Full Text Available The interplay between clouds and aerosols and their contribution to the radiation budget is one of the largest uncertainties of climate change. Most work to date has separated cloudy and cloud-free areas in order to evaluate the individual radiative forcing of aerosols, clouds, and aerosol effects on clouds.

    Here we examine the size distribution and the optical properties of small, sparse cumulus clouds and the associated optical properties of what is considered a cloud-free atmosphere within the cloud field. We show that any separation between clouds and cloud free atmosphere will incur errors in the calculated radiative forcing.

    The nature of small cumulus cloud size distributions suggests that at any resolution, a significant fraction of the clouds are missed, and their optical properties are relegated to the apparent cloud-free optical properties. At the same time, the cloudy portion incorporates significant contribution from non-cloudy pixels.

    We show that the largest contribution to the total cloud reflectance comes from the smallest clouds and that the spatial resolution changes the apparent energy flux of a broken cloudy scene. When changing the resolution from 30 m to 1 km (Landsat to MODIS the average "cloud-free" reflectance at 1.65 μm increases from 0.0095 to 0.0115 (>20%, the cloud reflectance decreases from 0.13 to 0.066 (~50%, and the cloud coverage doubles, resulting in an important impact on climate forcing estimations. The apparent aerosol forcing is on the order of 0.5 to 1 Wm−2 per cloud field.

  7. Diagnostic Value of Serum Pro-gastrin-releasing Peptide and Neuron-specific Enolase for Small Cell Lung Cancer and Its Influencing Factors%血清胃泌素释放肽前体和神经元烯醇化酶在小细胞肺癌的辅助诊断作用及影响因素

    Institute of Scientific and Technical Information of China (English)

    郭子建; 刘茜; 夏良裕; 程歆琦; 刘中娟; 张瑞丽; 韩慧娟; 秦绪珍; 张力; 柳涛; 李雪; 肖雨


    Objective To investigate the clinical significance and influencing factors of serum levels of pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) in the diagnosis of small cell lung cancer ( SCLC) .Methods The levels of serum ProGRP and NSE in 93 SCLC patients ( SCLC group ) , 120 non-small cell lung cancer (NSCLC) patients (NSCLC group), 120 benign pulmonary disease patients (benign disease group ) , and 90 healthy people ( healthy control group ) were determined using enzyme-linked immunosor-bent assay (ELISA).The potential impacts of the hemolysis in samples and impaired renal function on ProGRP and NSE were tested via electroluminescent and chemiluminescent immunoassay , respectively .Results The ser-um ProGRP and NSE concentrations were 90.61 (11.75-20 020.90) ng/L and 13.18 (3.05-201.88) μg/L, respectively , in SCLC group;13.26 (8.54-526.23) ng/L and 5.86 (1.80-100.90) μg/L in NSCLC group;24.65 (1.32 -802.93) ng/L and 7.22 (1.36-174.62 ) μg/L in benign disease group; and 14.74 (4.59 -100.86) ng/L and 4.95 (1.31-10.58 ) μg/L in healthy control group .The levels in the SCLC group were sig-nificantly different from those in the other three groups ( all P<0.01 ) .The area under the receiver operating characteristic curve of ProGRP was (0.856 ±0.023) (95%CI:0.811-0.901).When the cutoff value of Pro-GRP was set at 46 ng/L, the diagnostic sensitivity , specificity , positive predictive value , negative predictive val-ue, and Youden's index were 64.5% (60/93), 94.2%(311/330), 75.9%(60/79), 90.4%(311/344), and 58.7%, respectively , showing good detection performance .Sample hemolysis seriously improved the detec-tion results of NSE .Patients with impaired renal function had higher ProGRP levels .Conclusions The serum ProGRP and NSE levels are valuable tumor markers for the diagnosis of SCLC .Detection of both markers are par-ticularly useful for the monitoring of SCLC .Sample hemolysis may seriously increase the detected NSE level , whereas

  8. MINERVA: Small Planets from Small Telescopes (United States)

    Wittenmyer, Robert A.; Johnson, John Asher; Wright, Jason; McCrady, Nate; Swift, Jonathan; Bottom, Michael; Plavchan, Peter; Riddle, Reed; Muirhead, Philip S.; Herzig, Erich; Myles, Justin; Blake, Cullen H.; Eastman, Jason; Beatty, Thomas G.; Lin, Brian; Zhao, Ming; Gardner, Paul; Falco, Emilio; Criswell, Stephen; Nava, Chantanelle; Robinson, Connor; Hedrick, Richard; Ivarsen, Kevin; Hjelstrom, Annie; Vera, Jon De; Szentgyorgyi, Andrew


    The Kepler mission has shown that small planets are extremely common. It is likely that nearly every star in the sky hosts at least one rocky planet. We just need to look hard enough-but this requires vast amounts of telescope time. MINERVA (MINiature Exoplanet Radial Velocity Array) is a dedicated exoplanet observatory with the primary goal of discovering rocky, Earth-like planets orbiting in the habitable zone of bright, nearby stars. The MINERVA team is a collaboration among UNSW Australia, Harvard-Smithsonian Center for Astrophysics, Penn State University, University of Montana, and the California Institute of Technology. The four-telescope MINERVA array will be sited at the F.L. Whipple Observatory on Mt Hopkins in Arizona, USA. Full science operations will begin in mid-2015 with all four telescopes and a stabilised spectrograph capable of high-precision Doppler velocity measurements. We will observe ~100 of the nearest, brightest, Sun-like stars every night for at least five years. Detailed simulations of the target list and survey strategy lead us to expect new low-mass planets.

  9. Certifiable Specification and Verification of C Programs (United States)

    Lüth, Christoph; Walter, Dennis

    A novel approach to the specification and verification of C programs through an annotation language that is a mixture between JML and the language of Isabelle/HOL is proposed. This yields three benefits: specifications are concise and close to the underlying mathematical model; existing Isabelle theories can be reused; and the leap of faith from specification language to encoding in a logic is small. This is of particular relevance for software certification, and verification in application areas such as robotics.

  10. Small hydroelectric engineering practice

    CERN Document Server

    Leyland, Bryan


    Small Hydroelectric Engineering Practice is a comprehensive reference book covering all aspects of identifying, building, and operating hydroelectric schemes between 500 kW and 50 MW. In this range of outputs there are many options for all aspects of the scheme and it is very important that the best options are chosen.As small hydroelectric schemes are usually built against a limited budget it is extremely important that the concept design is optimum and every component is designed to maximise the benefi t and minimise the cost. As operating costs are often a high proportion of the income it i

  11. Small-Gap Flows (United States)


    34’OF CALIFORNIA# BERKELEY, CA 5.1720 ft (45 642-141 SMALL- GAP FLOWS BY E. 0. TUCK REPORT No. NAUE 84-1 CONTRACT N00014-84-K-OU26 APRIL i984...Mechanics, 41 (1970) 769-792. 11 3. Shallow-Water Waves at Discontinuities Shallow-water waves represent perhaps the prototype small- gap flow , the...solving (4.4) we need "initial" conditions at the starting station z = 0, and "exit" conditions at the station z = L where the gap flow merges with the

  12. Design of ground segments for small satellites (United States)

    Mace, Guy


    New concepts must be implemented when designing a Ground Segment (GS) for small satellites to conform to their specific mission characteristics: low cost, one main instrument, spacecraft autonomy, optimized mission return, etc. This paper presents the key cost drivers of such ground segments, the main design features, and the comparison of various design options that can meet the user requirements.

  13. Administrative Procedures for Small Institutions. Second Edition. (United States)

    Mathews, Keith W., Ed.

    This guide offers sample administrative procedures and policies that can be used by small colleges and universities to prepare or revise administrative procedures manuals. The sample procedures and policies offered here have been compiled from a review of many manuals from many different institutions, and vary from the general to the specific.…

  14. Small and mid-sized carnivores (United States)

    Steven W. Buskirk; William J. Zielinski


    Small and mid-sized carnivores of western forests represent an ecologically diverse and influential guild of forest vertebrates. They comprise over a dozen species with varied life histories and habitat associations, highly species-specific responses to human-caused habitat change, and varied conservation status across western North America. Forested habitats fulfill...

  15. Imaging the small bowel.

    LENUS (Irish Health Repository)

    Murphy, Kevin P


    Radiologic investigations continue to play a pivotal role in the diagnosis of pathologic conditions of the small intestine despite enhancement of capsule endoscopy and double-balloon endoscopy. Imaging techniques continue to evolve and new techniques in MRI in particular, are being developed.

  16. Light within small particles

    Energy Technology Data Exchange (ETDEWEB)

    Iati, Maria Antonia [Dipartimento di Fisica della Materia e Tecnologie Fisiche Avanzate, Universita di Messina, Salita Sperone, 31 - 98166 Messina (Italy)]. E-mail:; Saija, Rosalba [Dipartimento di Fisica della Materia e Tecnologie Fisiche Avanzate, Universita di Messina, Salita Sperone, 31 - 98166 Messina (Italy); Giusto, Arianna [Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Denti, Paolo [Dipartimento di Fisica della Materia e Tecnologie Fisiche Avanzate, Universita di Messina, Salita Sperone, 31 - 98166 Messina (Italy); Borghese, Ferdinando [Dipartimento di Fisica della Materia e Tecnologie Fisiche Avanzate, Universita di Messina, Salita Sperone, 31 - 98166 Messina (Italy); Cecchi-Pestellini, Cesare [Osservatorio Astronomico di Cagliari, Strada n.54, Loc. Poggio dei Pini, 09012 Capoterra (CA) (Italy)


    We calculate the energy density distribution in the ultraviolet within small spheres containing concentric cavities, aimed at simulating interstellar dust grains. We explore the dependence on chemical composition by progressively changing, in an arbitrary way, the refractive index of the sphere material. We conclude that a significant fraction of the energy of the impinging radiation is trapped throughout the particle interior.

  17. small Cell Lung Cancer

    African Journals Online (AJOL)

    treatment response in a non-small cell lung cancer (NSCLC). Methodology: A single-center ..... groupings in the forthcoming (7th) edition of the TNM. Classification of ... overall survival in patients with metastatic colorectal cancer. J Clin Oncol ...

  18. Small Modular Biomass Systems

    Energy Technology Data Exchange (ETDEWEB)



    This fact sheet provides information about modular biomass systems. Small modular biomass systems can help supply electricity to rural areas, businesses, and the billions of people who live without power worldwide. These systems use locally available biomass fuels such as wood, crop waste, animal manures, and landfill gas.

  19. Small bowel resection - discharge (United States)

    ... that rubs against your wound while it is healing. Use a thin gauze pad over it to protect it if needed. If you have an ileostomy, follow care instructions from your provider. Diet Eat small amounts of food several times a day. DO NOT eat 3 ...

  20. Small holding circles

    CERN Document Server

    Fruchard, Augustin


    A circle C holds a convex body K if C does not meet the interior of K and if there does not exist any euclidean displacement which moves C as far as desired from K, avoiding the interior of K. The purpose of this note is to explore how small can be a holding circle.

  1. Small Group Research (United States)

    McGrath, Joseph E.


    Summarizes research on small group processes by giving a comprehensive account of the types of variables primarily studied in the laboratory. These include group structure, group composition, group size, and group relations. Considers effects of power, leadership, conformity to social norms, and role relationships. (Author/AV)

  2. On a small Monacanthus

    NARCIS (Netherlands)

    Popta, C.M.L.


    Among fishes sent to the Leyden Museum by the late Dr. Bleeker, I found a Monacanthus which I cannot bring to one of the described species. It is a small specimen and it may be young, it is however interesting on account of its beautiful markings. When later on more or larger specimens will be found

  3. Deburring small intersecting holes

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.


    Deburring intersecting holes is one of the most difficult deburring tasks faced by many industries. Only 14 of the 37 major deburring processes are applicable to most intersecting hole applications. Only five of these are normally applicable to small or miniature holes. Basic process capabilities and techniques used as a function of hole sizes and intersection depths are summarized.

  4. Extrapulmonary small cell carcinoma.

    NARCIS (Netherlands)

    Heijden, E. van der; Heijdra, Y.F.


    This article reviews the recent literature on extrapulmonary small cell carcinomas. Until now, only four cases have been published in the English literature, two of those in the Southern Medical Journal. Sharing the information on diagnosis and treatment of these cases is important for better unders

  5. Small Public Library Management (United States)

    Pearlmutter, Jane; Nelson, Paul


    Anyone at the helm of a small public library knows that every little detail counts. But juggling the responsibilities that are part and parcel of the job is far from easy. Finally, here's a handbook that includes everything administrators need to keep a handle on library operations, freeing them up to streamline and improve how the organization…

  6. Small and Magical

    Institute of Scientific and Technical Information of China (English)


    Ant genome study offers promising evidence in medical and anti-aging research While children often love observing ants happily for hours, grownups are more likely to ignore these small creatures. Some scientists, however, show greater interest in ants than children do.

  7. Small Bowel Lymphangioma

    Directory of Open Access Journals (Sweden)

    Shou-jiang Tang


    Conclusions: Small bowel lymphangiomas can cause gross or occult GI bleeding, anemia, abdominal pain, and/or obstruction. Endoscopists should be aware of this rare tumor and its unique endoscopic features. The optimal treatment is radical excision, since incomplete resection may lead to recurrence. Argon plasma coagulation or polypectomy have been used to achieve endoscopic ablation and palliation of GI bleeding.

  8. Composition of Solar System Small Bodies

    CERN Document Server

    Vernazza, Pierre


    The aim of the chapter is to summarize our understanding of the compositional distribution across the different reservoirs of small bodies (main belt asteroids, giant planet trojans, irregular satellites of the giant planets, TNOs, comets). We then use this information to i) discuss current dynamical models (Nice and Grand Tack models), ii) mention possible caveats in these models if any, and iii) draw a preliminary version of the primordial compositional gradient across the solar system before planetary migrations occured. Note that the composition of both planetary satellites (the regular ones) and that of the transient populations (NEOs, centaurs) is not discussed here. We strictly focus on the composition of the main reservoirs of small bodies. The manuscript's objective is to provide a global and synthetic view of small bodies' compositions rather than a very detailed one, for specific reviews regarding the composition of small bodies, see papers by Burbine (2014) for asteroids, Emery et al. (2015) for J...

  9. Hidden layers of human small RNAs

    DEFF Research Database (Denmark)

    Kawaji, Hideya; Nakamura, Mari; Takahashi, Yukari;


    shows that well-characterized non-coding RNA, such as tRNA, snoRNA, and snRNA are cleaved at sites specific to the class of ncRNA. In particular, tRNA cleavage is regulated depending on tRNA type and tissue expression. We also found small RNAs mapped to genomic regions that are transcribed in both...... small RNA have focused on miRNA and/or siRNA rather than on the exploration of additional classes of RNAs. RESULTS: Here, we explored human small RNAs by unbiased sequencing of RNAs with sizes of 19-40 nt. We provide substantial evidences for the existence of independent classes of small RNAs. Our data...

  10. 78 FR 11745 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small... (United States)


    ... / Wednesday, February 20, 2013 / Rules and Regulations#0;#0; ] SMALL BUSINESS ADMINISTRATION 13 CFR Part 121 RIN 3245-AG46 Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small Business Technology Transfer (STTR) Program; Correction AGENCY: U.S. Small Business...

  11. Small Spacecraft for Planetary Science (United States)

    Baker, John; Castillo-Rogez, Julie; Bousquet, Pierre-W.; Vane, Gregg; Komarek, Tomas; Klesh, Andrew


    As planetary science continues to explore new and remote regions of the Solar system with comprehensive and more sophisticated payloads, small spacecraft offer the possibility for focused and more affordable science investigations. These small spacecraft or micro spacecraft (electronics, advanced manufacturing for lightweight structures, and innovative propulsion are making it possible to fly much more capable micro spacecraft for planetary exploration. While micro spacecraft, such as CubeSats, offer significant cost reductions with added capability from advancing technologies, the technical challenges for deep space missions are very different than for missions conducted in low Earth orbit. Micro spacecraft must be able to sustain a broad range of planetary environments (i.e., radiations, temperatures, limited power generation) and offer long-range telecommunication performance on a par with science needs. Other capabilities needed for planetary missions, such as fine attitude control and determination, capable computer and data handling, and navigation are being met by technologies currently under development to be flown on CubeSats within the next five years. This paper will discuss how micro spacecraft offer an attractive alternative to accomplish specific science and technology goals and what relevant technologies are needed for these these types of spacecraft. Acknowledgements: Part of this work is being carried out at the Jet Propulsion Laboratory, California Institute of Technology under contract to NASA. Government sponsorship acknowledged.

  12. Small Multiples with Gaps. (United States)

    Meulemans, Wouter; Dykes, Jason; Slingsby, Aidan; Turkay, Cagatay; Wood, Jo


    Small multiples enable comparison by providing different views of a single data set in a dense and aligned manner. A common frame defines each view, which varies based upon values of a conditioning variable. An increasingly popular use of this technique is to project two-dimensional locations into a gridded space (e.g. grid maps), using the underlying distribution both as the conditioning variable and to determine the grid layout. Using whitespace in this layout has the potential to carry information, especially in a geographic context. Yet, the effects of doing so on the spatial properties of the original units are not understood. We explore the design space offered by such small multiples with gaps. We do so by constructing a comprehensive suite of metrics that capture properties of the layout used to arrange the small multiples for comparison (e.g. compactness and alignment) and the preservation of the original data (e.g. distance, topology and shape). We study these metrics in geographic data sets with varying properties and numbers of gaps. We use simulated annealing to optimize for each metric and measure the effects on the others. To explore these effects systematically, we take a new approach, developing a system to visualize this design space using a set of interactive matrices. We find that adding small amounts of whitespace to small multiple arrays improves some of the characteristics of 2D layouts, such as shape, distance and direction. This comes at the cost of other metrics, such as the retention of topology. Effects vary according to the input maps, with degree of variation in size of input regions found to be a factor. Optima exist for particular metrics in many cases, but at different amounts of whitespace for different maps. We suggest multiple metrics be used in optimized layouts, finding topology to be a primary factor in existing manually-crafted solutions, followed by a trade-off between shape and displacement. But the rich range of possible

  13. Characterization of Small (Energy CT. (United States)

    Patel, Bhavik N; Bibbey, Alex; Choudhury, Kingshuk R; Leder, Richard A; Nelson, Rendon C; Marin, Daniele


    The purpose of this study is to determine whether single-phase contrast-enhanced dual-energy quantitative spectral analysis improves the accuracy of diagnosis of small (energy attenuation measurements. In this retrospective study, 136 consecutive patients (95 men and 41 women; mean age, 54 years) with 144 renal lesions (111 benign and 33 malignant) underwent single-energy unenhanced and dual-energy contrast-enhanced CT of the abdomen. For each renal lesion, attenuation measurements were obtained, and an attenuation change of 15 HU or greater was considered evidence of enhancement. Dual-energy spectral attenuation curves were generated for each lesion. The slope of each curve was measured between 40 and 50 keV (λHU40-50), 40 and 70 keV (λHU40-70), and 40 and 140 keV (λHU40-140). Mean lesion attenuation values and spectral attenuation curve parameters were compared between benign and malignant renal lesions by use of the two-sample t test. Diagnostic accuracy was assessed and validated using cross-validation analysis. With the use of cross-validated optimal thresholds at 100% sensitivity, specificity for differentiating between benign and malignant renal lesions improved significantly when both λHU40-70 and λHU40-140 were used, compared with conventional enhancement measurements (93% [103/111; 95% CI, 86-97%] vs 81% [90/111; 95% CI, 73-88%]) (p = 0.02). The sensitivity of λHU40-70 and λHU40-140 was also higher than that of conventional enhancement measurements, although it was not statistically significant. Single-phase contrast-enhanced dual-energy quantitative spectral analysis significantly improves the specificity for characterization of small (energy attenuation measurements.

  14. Small Engine & Accessory Test Area (United States)

    Federal Laboratory Consortium — The Small Engine and Accessories Test Area (SEATA) facilitates testaircraft starting and auxiliary power systems, small engines and accessories. The SEATA consists...

  15. Small Wind Energy Systems

    DEFF Research Database (Denmark)


    This chapter intends to serve as a brief guide when someone is considering the use of wind energy for small power applications. It is discussed that small wind energy systems act as the major energy source for residential or commercial applications, or how to make it part of a microgrid...... as a distributed generator. In this way, sources and loads are connected in such a way to behave as a renewable dispatch center. With this regard, non-critical loads might be curtailed or shed during times of energy shortfall or periods of high costs of energy production. If such a wind energy system is connected...... to the public distibutor, it can serve as a backup system, as a non-interruptible power supply (with storage aggregation), provide low-voltage support, or give a clean surplus of energy transferred to the public network under economical and technological basis. In this chapter, several factors are also...

  16. Aerodynamics of Small Vehicles (United States)

    Mueller, Thomas J.

    In this review we describe the aerodynamic problems that must be addressed in order to design a successful small aerial vehicle. The effects of Reynolds number and aspect ratio (AR) on the design and performance of fixed-wing vehicles are described. The boundary-layer behavior on airfoils is especially important in the design of vehicles in this flight regime. The results of a number of experimental boundary-layer studies, including the influence of laminar separation bubbles, are discussed. Several examples of small unmanned aerial vehicles (UAVs) in this regime are described. Also, a brief survey of analytical models for oscillating and flapping-wing propulsion is presented. These range from the earliest examples where quasi-steady, attached flow is assumed, to those that account for the unsteady shed vortex wake as well as flow separation and aeroelastic behavior of a flapping wing. Experiments that complemented the analysis and led to the design of a successful ornithopter are also described.

  17. Small Business Innovations (United States)


    The purpose of QASE RT is to enable system analysts and software engineers to evaluate performance and reliability implications of design alternatives. The program resulted from two Small Business Innovation Research (SBIR) projects. After receiving a description of the system architecture and workload from the user, QASE RT translates the system description into simulation models and executes them. Simulation provides detailed performance evaluation. The results of the evaluations are service and response times, offered load and device utilizations and functional availability.

  18. Small Generation Gap

    Institute of Scientific and Technical Information of China (English)



    IT was while I was making milk for my son that I discovered the generation gap between us. A little thing of two years and three months, my son stood on a big chair I brought him and joined me to make milk. Holding a small spoon in his plump little hand, he scooped flour out of a jar and poured it into the feeding bottle and then scooped milk powder and

  19. Small and Magical

    Institute of Scientific and Technical Information of China (English)



    While children often love observing ants happily for hours,grown-ups are more likely to ignore these small creatures.Some scientists,however,show greater interest in ants than children do.One of them is Zhang Guojie,Associate Director of the Bioinformatics Center and Leader of Genome Projects in BGI.BG1 is China's largest genome and bioinformatics analysis center in Shenzhen,in south China's Guangdong Province.

  20. When small is beautiful. Boom time for small hydro?

    Energy Technology Data Exchange (ETDEWEB)

    Osborne, John


    Although small hydropower projects generally contribute a small proportion of most nations' electricity needs their importance often exceeds their size. The author, a freelance industrial journalist considers prospects for small hydro, how such schemes are benefiting communities throughout the world and why some countries are more successfully using small hydro than others. (Author)





    Development of small injection moulding machine for forming small plastic articles in small-scale industries was studied. This work which entailed design, construction and test small injection moulding machine that was capable of forming small plastic articles by injecting molten resins into a closed, cooled mould, where it solidifies to give the desired products was developed. The machine was designed and constructed to work as a prototype for producing very small plastic components. Design ...

  2. Ecology in Small Aquatic Ecosystems

    DEFF Research Database (Denmark)

    Andersen, Mikkel René

    Small ecosystems are many-fold more abundant than their larger counterparts. Both on regional and global scale small lakes outnumber medium and large lakes and account for a much larger surface area. Small streams are also far more common than rivers. Despite their abundance small ecosystems are ...

  3. Ecology in Small Aquatic Ecosystems

    DEFF Research Database (Denmark)

    Andersen, Mikkel René

    Small ecosystems are many-fold more abundant than their larger counterparts. Both on regional and global scale small lakes outnumber medium and large lakes and account for a much larger surface area. Small streams are also far more common than rivers. Despite their abundance small ecosystems are ...

  4. The small library manager's handbook

    CERN Document Server

    Graves, Alice


    The Small Library Manager's Handbook is for librarians working in all types of small libraries. It covers the everyday nuts-and-bolts operations that all librarians must perform. This handbook, written by experts who are small librarians themselves, will help all small librarians to do multiple jobs at the same time.

  5. The Small Mars System (United States)

    Fantino, E.; Grassi, M.; Pasolini, P.; Causa, F.; Molfese, C.; Aurigemma, R.; Cimminiello, N.; de la Torre, D.; Dell'Aversana, P.; Esposito, F.; Gramiccia, L.; Paudice, F.; Punzo, F.; Roma, I.; Savino, R.; Zuppardi, G.


    The Small Mars System is a proposed mission to Mars. Funded by the European Space Agency, the project has successfully completed Phase 0. The contractor is ALI S.c.a.r.l., and the study team includes the University of Naples ;Federico II;, the Astronomical Observatory of Capodimonte and the Space Studies Institute of Catalonia. The objectives of the mission are both technological and scientific, and will be achieved by delivering a small Mars lander carrying a dust particle analyser and an aerial drone. The former shall perform in situ measurements of the size distribution and abundance of dust particles suspended in the Martian atmosphere, whereas the latter shall demonstrate low-altitude flight in the rarefied planetary environment. The mission-enabling technology is an innovative umbrella-like heat shield, known as IRENE, developed and patented by ALI. The mission is also a technological demonstration of the shield in the upper atmosphere of Mars. The core characteristics of SMS are the low cost (120 M€) and the small size (320 kg of wet mass at launch, 110 kg at landing), features which stand out with respect to previous Mars landers. To comply with them is extremely challenging at all levels, and sets strict requirements on the choice of the materials, the sizing of payloads and subsystems, their arrangement inside the spacecraft and the launcher's selection. In this contribution, the mission and system concept and design are illustrated and discussed. Special emphasis is given to the innovative features and to the challenges faced in the development of the work.

  6. Small Unit Operations (United States)


    best demonstrated value for small (< AA size) lithium - thionyl - chloride batteries (Halpert 1993). Equation (2-3) shows that the solar power...However, this energy den- sity this is only ~ 3 times larger than the demonstrated performance of the best lithium batteries , and the fuel cells are...Units 13 2.2.2 ASIC Capability 15 2.2.3 Power and Size 17 2.2.4 Cost 19 2.3 Power Sources 20 2.3.1 Batteries 21 2.3.2 Solar Augmentation

  7. Small hydro in Africa

    CSIR Research Space (South Africa)

    Jonker Klunne, W


    Full Text Available stream_source_info Klunne1_2011.pdf.txt stream_content_type text/plain stream_size 12260 Content-Encoding ISO-8859-1 stream_name Klunne1_2011.pdf.txt Content-Type text/plain; charset=ISO-8859-1 INTERNATIONAL WATER POWER..., only 4 to 7% of the potential for large scale hydropower has been exploited [1,2]. For small and micro scale hydropower this percentage is most probably even lower, although no proper statistics are available. To indicate the low rate...

  8. SmallSat Lab (United States)


    CubeSat. Mr. Alvarez worked with four students on the PCB layout for the solar panels and the construction of the 6U CubeSat mockup . Support for Mr...Hull and Mr. Alvarez was $49k including fringe benefits. !! Purchases: During this time period a license for MatLab software and the Princeton...Satellite ToolBox was purchased using funds from this award. This software adds tremendous capability to the SmallSat Lab by enabling students to analyze

  9. Small changes for works

    Institute of Scientific and Technical Information of China (English)

    Jiarui Wu


    The central dogma of molecular biology indicates that genetic information from DNA is transmitted to RNA,and then translated into proteins that play various roles during all physiological and pathological processes.However,most of the proteins have to make small chemical changes on their amino acid chains,so-called post-translational modifications,before they start to work.The collection of four articles in this issue presents timely developments in the area of protein modifications,ranging from how proteins carry out their biological functions based on protein modifications to what are molecular mechanisms of protein modifications.

  10. Urine specific gravity test (United States)

    ... Urine specific gravity test To use the sharing features on this page, please enable JavaScript. Urine specific gravity is a laboratory test that shows the concentration ...

  11. Phobia - simple/specific (United States)

    Anxiety disorder - phobia ... Specific phobias are a type of anxiety disorder in which a person may feel extremely anxious or has a ... when exposed to the object of fear. Specific phobias are a common mental disorder. Common phobias include ...

  12. Small engine technology programs (United States)

    Niedzwiecki, Richard W.


    Described here is the small engine technology program being sponsored at the Lewis Research Center. Small gas turbine research is aimed at general aviation, commuter aircraft, rotorcraft, and cruise missile applications. The Rotary Engine program is aimed at supplying fuel flexible, fuel efficient technology to the general aviation industry, but also has applications to other missions. The Automotive Gas Turbine (AGT) and Heavy-Duty Diesel Transport Technology (HDTT) programs are sponsored by DOE. The Compound Cycle Engine program is sponsored by the Army. All of the programs are aimed towards highly efficient engine cycles, very efficient components, and the use of high temperature structural ceramics. This research tends to be generic in nature and has broad applications. The HDTT, rotary technology, and the compound cycle programs are all examining approaches to minimum heat rejection, or 'adiabatic' systems employing advanced materials. The AGT program is also directed towards ceramics application to gas turbine hot section components. Turbomachinery advances in the gas turbine programs will benefit advanced turbochargers and turbocompounders for the intermittent combustion systems, and the fundamental understandings and analytical codes developed in the research and technology programs will be directly applicable to the system projects.

  13. Role of the Rubisco Small Subunit

    Energy Technology Data Exchange (ETDEWEB)

    Spreitzer, Robert Joseph [Univ. of Nebraska, Lincoln, NE (United States)


    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate-limiting step of CO2 fixation in photosynthesis. However, it is a slow enzyme, and O2 competes with CO2 at the active site. Oxygenation initiates the photorespiratory pathway, which also results in the loss of CO2. If carboxylation could be increased or oxygenation decreased, an increase in net CO2 fixation would be realized. Because Rubisco provides the primary means by which carbon enters all life on earth, there is much interest in engineering Rubisco to increase the production of food and renewable energy. Rubisco is located in the chloroplasts of plants, and it is comprised of two subunits. Much is known about the chloroplast-gene-encoded large subunit (rbcL gene), which contains the active site, but much less is known about the role of the nuclear-gene-encoded small subunit in Rubisco function (rbcS gene). Both subunits are coded by multiple genes in plants, which makes genetic engineering difficult. In the eukaryotic, green alga Chlamydomonas reinhardtii, it has been possible to eliminate all the Rubisco genes. These Rubisco-less mutants can be maintained by providing acetate as an alternative carbon source. In this project, focus has been placed on determining whether the small subunit might be a better genetic-engineering target for improving Rubisco. Analysis of a variable-loop structure (βA-βB loop) of the small subunit by genetic selection, directed mutagenesis, and construction of chimeras has shown that the small subunit can influence CO2/O2 specificity. X-ray crystal structures of engineered chimeric-loop enzymes have indicated that additional residues and regions of the small subunit may also contribute to Rubisco function. Structural dynamics of the small-subunit carboxyl terminus was also investigated. Alanine-scanning mutagenesis of the most-conserved small-subunit residues has identified a

  14. Transforming a small business: A learning intervention

    Directory of Open Access Journals (Sweden)

    Dirk J. Geldenhuys


    Full Text Available Orientation: This article reports on a learning intervention in a brokers company with fewer than 50 employees. A rich description of the participants’ experience is provided. Research purpose: The purpose of the study was to explore the use of an experiential learning process during an organisation development (OD intervention in a small business by means of a case study.Motivation for the study: This study explored the important role of small businesses; the role of management; and, more specifically, organisation development models that were developed for large corporations; as these emphasise the need to study the purpose of organisation development interventions in small businesses.Research design, approach and method: The study reported on in this article was a qualitative case study in a small brokers company with 21 staff members. The data were analysed manually by means of qualitative content analysis.Main findings: The main finding of the research concerned how experiential learning intervention provided a space for participants to start exploring, and gradually changing the dynamics of their small business, by transforming their business into a more formal company.Practical/managerial implications: The primary implication is that experiential learning interventions that are operationalised, from a psychodynamic perspective, can be valuable when consulted by small businesses during their transformation towards becoming more formal companies.Contribution/value-add: This article contributes to the OD literature on small businesses, with fewer than 50 employees, by providing data on how the learning process, that commenced during an experiential learning intervention, assisted a small company to develop its identity towards that of a more formal company.

  15. Mechanical design and development aspects of a small AUV - Maya

    Digital Repository Service at National Institute of Oceanography (India)

    Madhan, R.; Desa, E.S.; Prabhudesai, S.; Sebastiao, L.; Pascoal, A; Desa, E.; Mascarenhas, A.A; Maurya, P.; Navelkar, G.S.; Afzulpurkar, S.; Khalap, S.

    This paper contains a description of the mechanical design route that was adopted in building a small AUV (Autonomous Underwater Vehicle). At the outset, it is decided to follow a set of guidelines that defined a broad set of specifications...

  16. The SIFT Code Specification (United States)


    The specification of Software Implemented Fault Tolerance (SIFT) consists of two parts, the specifications of the SIFT models and the specifications of the SIFT PASCAL program which actually implements the SIFT system. The code specifications are the last of a hierarchy of models describing the operation of the SIFT system and are related to the SIFT models as well as the PASCAL program. These Specifications serve to link the SIFT models to the running program. The specifications are very large and detailed and closely follow the form and organization of the PASCAL code. In addition to describing each of the components of the SIFT code, the code specifications describe the assumptions of the upper SIFT models which are required to actually prove that the code will work as specified. These constraints are imposed primarily on the schedule tables.

  17. Protein Scaffolding for Small Molecule Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Baker, David [Univ. of Washington, Seattle, WA (United States)


    We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematically modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.

  18. Problems of Small Debris

    Directory of Open Access Journals (Sweden)

    V. V. Zelentsov


    Full Text Available During the exploration of outer space (as of 1/1 2011 6853 was launched spacecraft (SC are successful 6264, representing 95% of the total number of starts. The most intensively exploited space Russia (USSR (3701 starts, 94% successful, USA (2774 starts, 90% successful, China (234 starts, 96% successful and India (89 starts, 90% successful. A small part of running the spacecraft returned to Earth (manned spacecraft and transport, and the rest remained in orbit. Some of them are descended from orbit and burned up in the atmosphere, the rest remained in the OCP and turned into space debris (SD.The composition of the Cabinet is diverse: finish the job spacecraft; boosters and the last stage of launch vehicles left in orbit after SC injection; technological waste arising during the opening drop-down structures and fragments of the destroyed spacecraft. The resulting explosion orbital SD forms ellipsoidal region which orbits blasted object. Then, as a result of precession, is the distribution of objects in orbit explosion exploding spacecraft.The whole Cabinet is divided into two factions: the observed (larger than 100 mm and not observed (less than 100 mm. Observed debris katalogalizirovan and 0.2% of the total number of SD, there was no SD is the bulk - 99.8%.SC meeting working with a fragment observed SD predictable and due to changes in altitude spacecraft avoids a possible meeting. Contact spacecraft with large fragment lead to disaster (which took place at a meeting of the Russian communications satellite "Cosmos-2251" and the American machine "Iridium". Meeting with small SD is not predictable, especially if it was formed by an explosion or collision fragments together. Orbit that KM is not predictable, and the speed can be up to 10 km / s. Meeting with small particle SD no less dangerous for the spacecraft. The impact speed of spacecraft with space debris particles can reach up to 10 ... 15 km / s at such speeds the breakdown probability thin

  19. Small Wind Energy Systems

    DEFF Research Database (Denmark)

    Simoes, Marcelo; Farret, Felix Alberto; Blaabjerg, Frede


    devices, and a centralized distribution control. In order to establish a small wind energy system it is important to observe the following: (i) Attending the energy requirements of the actual or future consumers; (ii) Establishing civil liabilities in case of accidents and financial losses due to shortage...... or low quality of energy; (iii) Negotiating collective conditions to interconnect the microgrid with the public network or with other sources of energy that is independent of wind resources; (iv) Establishing a performance criteria of power quality and reliability to end-users, in order to reduce costs...... and guaranteeing an acceptable energy supply. This paper discuss how performance is affected by local conditions and random nature of the wind, power demand profiles, turbine related factors, and presents the technical issues for implementing a self-excited induction generator system, or a permanent magnet based...

  20. [Is allastrim small pox?]. (United States)

    Tiexeira, L A


    Between 1910 and 1913, two renowned physicians in the city of Sao Paulo found themselves engaged in a scientific controversy regarding the classification of a disease then assailing the state. Antonio Carini, director of the Instituto Pasteur de Sao Paulo, believed the illness to be small pox, while Emilio Ribas, director of the Servico Sanitario, claimed it was allastrim, or milk pox. The controversy started in the Sociedade de Medicina e Cirurgia but later migrated to other forums and came to incorporate other figures as well. This presentation and discussion of the polemic is meant as a contribution to our understanding of the process by which a scientific consensus is constructed and solidified within the field of the biomedical sciences.

  1. Rolling at small scales

    DEFF Research Database (Denmark)

    Nielsen, Kim L.; Niordson, Christian F.; Hutchinson, John W.


    The rolling process is widely used in the metal forming industry and has been so for many years. However, the process has attracted renewed interest as it recently has been adapted to very small scales where conventional plasticity theory cannot accurately predict the material response. It is well....... Metals are known to be stronger when large strain gradients appear over a few microns; hence, the forces involved in the rolling process are expected to increase relatively at these smaller scales. In the present numerical analysis, a steady-state modeling technique that enables convergence without...... dealing with the transient response period is employed. This allows for a comprehensive parameter study. Coulomb friction, including a stick-slip condition, is used as a first approximation. It is found that length scale effects increase both the forces applied to the roll, the roll torque, and thus...

  2. Modular small hydro configuration (United States)


    Smaller sites (those under 750 kilowatts) which previously were not attractive to develop using equipment intended for application at larger scale sites, were the focal point in the conception of a system which utilizes standard industrial components which are generally available within short procurement times. Such components were integrated into a development scheme for sites having 20 feet to 150 feet of head. The modular small hydro configuration maximizes the use of available components and minimizes modification of existing civil works. A key aspect of the development concept is the use of a vertical turbine multistage pump, used in the reverse mode as a hydraulic turbine. The configuration allows for automated operation and control of the hydroelectric facilities with sufficient flexibility for inclusion of potential hydroelectric sites into dispersed storage and generation (DSG) utility grid systems.

  3. Small intestinal transplantation.

    LENUS (Irish Health Repository)

    Quigley, E M


    The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.

  4. Amyloidosis of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Kala, Zdenek [Department of Surgery, Faculty Hospital Brno, Jihlavska 20, 62500 Brno (Czech Republic)]. E-mail:; Valek, Vlastimil [Department of Radiology, Faculty Hospital Brno, Jihlavska 20, 62500 Brno (Czech Republic)]. E-mail:; Kysela, Petr [Department of Surgery, Faculty Hospital Brno, Jihlavska 20, 62500 Brno (Czech Republic)]. E-mail:


    Amyloidosis is a rare disease characterized by forming pathological protein deposits - amyloid - in many organs and tissues. This decreases their functionality. The aim of this small study was to determine, whether the radiological picture of the small intestine involvement in amyloidosis is in some sense specific as sometimes described in literature giving rise to high suspicion for the disease in symptomatic patients. Material and methods: The prospective study comprising seven patients hospitalized in surgical department is presented together with a survey on the disease, its appearance in radiological imaging. All patients underwent abdominal ultrasound (ATL 5000 HDI, 7-12 MHz linear probe, no contrast enhancement, supine position), abdominal CT (Somatom Plus, Siemens, single detector, conventional abdominal CT protocol) and enteroclysis (Micropaque suspension 300 ml, application rate of 75 ml/min, dilution with HP-7000 being 1:1 and HP-7000 solution 2000 ml, application rate of 120 ml/min.). Results: The amyloid deposits in the small intestine could be visualized in five of seven patients with the disease. Enteroclysis revealed a diffuse slowed down intestinal motility with an obstruction-like picture in all of our seven patients. The intestinal secretion was normal, plicae were getting polyp-like shape in five of them forming so called 'thumb printing' picture. CT showed thickening of the intestinal wall due to deposits with poor blood supply and contrast retention in five of seven patients. Ultrasound visualized thickened, hypoechoic nodular plicae and slowed down motility in these five patients. The most striking finding was the pathological deposits in the intestinal wall were highly hypo-vascular. However, this picture is very similar to that of ischemic enteritis. All seven patients had proven amyloid deposits from bioptic specimens. Conclusion: The diagnosis of amyloidosis must be supported by bioptic examination as it has no pathognomic

  5. Small particle heat exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, A.J.


    A dispersion of small absorbing particles forms an ideal system to collect radiant energy, transform it to heat, and efficiently transfer the heat to a surrounding fluid. If the heated fluid is a pressurized gas, it can be passed through an expansion turbine to create useful mechanical energy. The most obvious application of this technique is its use in a solar collection system. In this case, the incoming sunlight is used to heat a compressed gas in an engine utilizing a Brayton cycle. The solar collection system may utilize high concentration as provided by a central receiver or parabolic dish, medium concentration from a linear collector, or possibly no concentration using a flat plate collector, if precautions were taken to reduce the heat losses. The same concept may be applied generally to non-solar heat exchangers. These may be of the type used to heat a gas from a combustion source, or in general as a gas to gas heat exchanger. The latter application may be limited to rather high temperature. Each of the above applications is discussed. First, a description of the concept is applied to a solar central-tower system. The general principles are described, including the optical and physical characteristics of the particles, the confinement of the gas-particle mixture, and the system considerations; the latter include the amount and type of particles, the receiver efficiency and the generation of the particles. The same considerations are reviewed for applications to linear trough and flat plate receivers. Finally, the use of small particles in non-solar heat exchangers is considered.

  6. Small rover exploration capabilities (United States)

    Salotti, Jean-Marc; Laithier, Corentin; Machut, Benoit; Marie, Aurélien; Bruneau, Audrey; Grömer, Gernot; Foing, Bernard H.


    For a human mission to the Moon or Mars, an important question is to determine the best strategy for the choice of surface vehicles. Recent studies suggest that the first missions to Mars will be strongly constrained and that only small unpressurized vehicles will be available. We analyze the exploration capabilities and limitations of small surface vehicles from the user perspective. Following the “human centered design” paradigm, the team focused on human systems interactions and conducted the following experiments: - Another member of our team participated in the ILEWG EuroMoonMars 2013 simulation at the Mars Desert Research Station in Utah during the same period of time. Although the possible traverses were restricted, a similar study with analog space suits and quads has been carried out. - Other experiments have been conducted in an old rock quarry close to Bordeaux, France. An expert in the use of quads for all types of terrains performed a demonstration and helped us to characterize the difficulties, the risks and advantages and drawbacks of different vehicles and tools. The vehicles that will be used on the surface of Mars have not been defined yet. Nevertheless, the results of our project already show that using a light and unpressurized vehicle (in the order of 150 kg) for the mobility on the Martian surface can be a true advantage. Part of the study was dedicated to the search for appropriate tools that could be used to make the vehicles easier to handle, safer to use and more efficient in the field to cross an obstacle. The final recommendation is to use winches and ramps, which already are widely used by quad drivers. We report on the extension of the reachable areas if such tools were available. This work has been supported by ILEWG, EuroMoonMars and the Austrian Space Forum (OEWF).

  7. Validation of Intraluminal and Intraperitoneal microdialysis in ischemic small intestine

    DEFF Research Database (Denmark)

    Pynnönen, Lauri; Minkkinen, Minna; Perner, Anders;


    We sought to define the sensitivity and specificity of intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in depicting ex vivo small intestinal total ischemia during GI-tract surgery. We hypothesized that IL as opposed to IP microdialysis detects small intestinal ischemia...

  8. Exploring Men's Perpetrator Programs in Small Rural Communities (United States)

    Jamieson, Shirley; Wendt, Sarah


    This paper outlines the findings of an exploratory study conducted in a small rural community in South Australia in 2006. Human service providers, experienced in working with victims and/or perpetrators of domestic violence, were asked about their experiences and perceptions of perpetrator programs in small rural communities. Specifically,…

  9. Small Business Management. Part I, A Suggested Course Outline. (United States)

    New York State Education Dept., Albany. Bureau of Continuing Education Curriculum Development.

    In this curriculum guide on small business management, lessons (including specific course content and teaching suggestions) are developed around general traits and practices conducive to success in small businesses, loans and other sources of capital, budgeting and planning, recordkeeping, marketing and selling, advertising and sales promotion,…

  10. Small-crack test methods (United States)

    Larsen, James M.; Allison, John E.

    This book contains chapters on fracture mechanics parameters for small fatigue cracks, monitoring small-crack growth by the replication method, measurement of small cracks by photomicroscopy (experiments and analysis), and experimental mechanics of microcracks. Other topics discussed are the real-time measurement of small-crack-opening behavior using an interferometric strain/displacement gage; direct current electrical potential measurement of the growth of small cracks; an ultrasonic method for the measurement of the size and opening behavior of small fatigue cracks; and the simulation of short crack and other low closure loading conditions, utilizing constant K(max) Delta-K-decreasing fatigue crack growth procedures.

  11. Developing a Small Business Regulatory System

    Directory of Open Access Journals (Sweden)

    Geoff Miller


    framework for small businesses it is important to weigh up the desire to minimise time spent by businesses on compliance, with maintaining the integrity of the market as a whole.People in my position rely on people like you with the specific knowledge and expertise in small business matters to make sure that reforms are developed which benefit both the small business sector and the wider economy.

  12. Detecting small low emission radiating sources

    CERN Document Server

    Allmaras, Moritz; Hristova, Yulia; Kanschat, Guido; Kuchment, Peter


    The article addresses the possibility of robust detection of geometrically small, low emission sources on a significantly stronger background. This problem is important for homeland security. A technique of detecting such sources using Compton type cameras is developed, which is shown on numerical examples to have high sensitivity and specificity and also allows to assign confidence probabilities of the detection. 2D case is considered in detail.

  13. Hydrophobic Porous Material Adsorbs Small Organic Molecules (United States)

    Sharma, Pramod K.; Hickey, Gregory S.


    Composite molecular-sieve material has pore structure designed specifically for preferential adsorption of organic molecules for sizes ranging from 3 to 6 angstrom. Design based on principle that contaminant molecules become strongly bound to surface of adsorbent when size of contaminant molecules is nearly same as that of pores in adsorbent. Material used to remove small organic contaminant molecules from vacuum systems or from enclosed gaseous environments like closed-loop life-support systems.

  14. Small and medium business in the contractual relationship system

    Directory of Open Access Journals (Sweden)

    Obalyaeva Julia, I.


    Full Text Available The paper reveals the role of small and medium business in the national economy. The comparative analysis of the indicators characterizing the development of small business in Russia, South Korea and France is given are compared. Two laws that support small and medium businesses in public purchasing. The author’s vision of the problems of development of small and medium-sized businesses in the Russian Federation and specification of the path of the national economy development is presented. Two schemes, revealing the organization of interaction of large corporate sector and the sector of small and medium-sized enterprises in the system of contractual relations and analysis of internal and external factors in the development of small and medium-sized enterprises are presented. The experience of conducting digital auctions with participation of small businesses on an digital platform CJSC "Sberbank AST" is considered.

  15. Small Business's Big Training Needs. (United States)

    Kelly, Leslie


    Discusses the training needs of small businesses in light of their high failure rate (50 percent). Includes characteristics of successful small businesses, potential training needs, training methods, and topics for seminars. (JOW)

  16. Small intestine contrast injection (image) (United States)

    ... and throat, through the stomach into the small intestine. When in place, contrast dye is introduced and ... means of demonstrating whether or not the small intestine is normal when abnormality is suspected.

  17. Small Area Fair Market Rent (United States)

    Department of Housing and Urban Development — Due to the increasing demand for more localized rents for a variety of purposes, HUD is making Small Area FMRs for all metropolitan areas available. Small Area FMRs...

  18. Small intestine aspirate and culture (United States)

    ... ency/article/003731.htm Small intestine aspirate and culture To use the sharing features on this page, please enable JavaScript. Small intestine aspirate and culture is a lab test to check for infection ...

  19. Formal versus informal small businesses

    African Journals Online (AJOL)

    There is renewed interest in entrepreneurship, business formation and growth. ... acumen, while small formal businesses show higher levels of growth instigated by an ... Small business support strategies should focus on businesses with ...

  20. Entrepreneurship and small business sustainability

    African Journals Online (AJOL)

    Southern African Business Review Volume 14 Number 3 2010. Entrepreneurship and small ... 16Key words: entrepreneurship, small business development, business sustainability, competition ...... Boston, MA: Harvard. Business School Press ...

  1. Globalization, Entrepreneurship and Small Business


    Stan ªtefania Anca


    New product innovation often comes from small business. Most the radical inventions of the last century, such as the computer, come from small companies, not large ones. And this will not change. Globalization will continue to modify and mold the environment or small business and entrepreneurship. The competition from abroad places strong pressure on small business in terms of efficiency, price, quality, cost, control, marketing, expertise, customer satisfaction and innovativeness. Globalizat...

  2. Experiences with effects specifications

    DEFF Research Database (Denmark)


    We describe the effects-specification process from a project that was conducted during the fall 2010 and spring of 2011 in this chapter. The project configured and implemented an electronic patient record system at a maternity ward at a hospital located in a European region. The process comprised...... for measuring effects were designed. The project is analyzed and lessons learned are discussed....... workshops with effects specification with management and end-users and an agile development process including prototypes configured from the effects specifications. We describe the project and the effects-specification process through which effects were related to the system design and instruments...

  3. Screening for Specific Phobias (United States)

    ... Disorder Specific Phobias Obsessive-Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) Depression Bipolar Disorder Suicide and Prevention Stress Related Illnesses Myth-Conceptions Find ...

  4. Lidar base specification (United States)

    Heidemann, Hans Karl.


    In late 2009, a $14.3 million allocation from the “American Recovery and Reinvestment Act” for new light detection and ranging (lidar) elevation data prompted the U.S. Geological Survey (USGS) National Geospatial Program (NGP) to develop a common base specification for all lidar data acquired for The National Map. Released as a draft in 2010 and formally published in 2012, the USGS–NGP “Lidar Base Specification Version 1.0” (now Lidar Base Specification) was quickly embraced as the foundation for numerous state, county, and foreign country lidar specifications.

  5. Competition between small RNAs: a quantitative view. (United States)

    Loinger, Adiel; Shemla, Yael; Simon, Itamar; Margalit, Hanah; Biham, Ofer


    Two major classes of small regulatory RNAs--small interfering RNAs (siRNAs) and microRNA (miRNAs)--are involved in a common RNA interference processing pathway. Small RNAs within each of these families were found to compete for limiting amounts of shared components, required for their biogenesis and processing. Association with Argonaute (Ago), the catalytic component of the RNA silencing complex, was suggested as the central mechanistic point in RNA interference machinery competition. Aiming to better understand the competition between small RNAs in the cell, we present a mathematical model and characterize a range of specific cell and experimental parameters affecting the competition. We apply the model to competition between miRNAs and study the change in the expression level of their target genes under a variety of conditions. We show quantitatively that the amount of Ago and miRNAs in the cell are dominant factors contributing greatly to the competition. Interestingly, we observe what to our knowledge is a novel type of competition that takes place when Ago is abundant, by which miRNAs with shared targets compete over them. Furthermore, we use the model to examine different interaction mechanisms that might operate in establishing the miRNA-Ago complexes, mainly those related to their stability and recycling. Our model provides a mathematical framework for future studies of competition effects in regulation mechanisms involving small RNAs.

  6. Quality and the Small School. (United States)

    Hildebrand, Edwin P., Ed.

    The 1965-1968 progress report of the Western States Small Schools Project focuses on the problem and challenge posed by small schools, which have thus far lacked the depth of resources compared to urban schools. The goals of the project are to assist small schools to: (1) provide individualized programs of career selection education; (2) develop…

  7. Neurological examination in small animals

    Directory of Open Access Journals (Sweden)

    Viktor Paluš


    Full Text Available This clinical review about the neurological examination in small animals describes the basics about the first steps of investigation when dealing with neurological patients. The knowledge of how to perform the neurological examination is important however more important is how to correctly interpret these performed tests. A step-by-step approach is mandatory and examiners should master the order and the style of performing these tests. Neurological conditions can be sometimes very distressing for owners and for pets that might not be the most cooperating. The role of a veterinary surgeon, as a professional, is therefore to collect the most relevant history, to examine a patient in a professional manner and to give to owners an educated opinion about the further treatment and prognosis. However neurological examinations might look challenging for many. But it is only the clinical application of neuroanatomy and neurophysiology to an every-day situation for practicing veterinarians and it does not require any specific in-to-depth knowledge. This clinical review is aimed not only to provide the information on how to perform the neurological examination but it is also aimed to appeal on veterinarians to challenge their daily routine and to start practicing on neurologically normal patients. This is the best and only way to differentiate between the normal and abnormal in a real situation.

  8. Small scale sanitation technologies. (United States)

    Green, W; Ho, G


    Small scale systems can improve the sustainability of sanitation systems as they more easily close the water and nutrient loops. They also provide alternate solutions to centrally managed large scale infrastructures. Appropriate sanitation provision can improve the lives of people with inadequate sanitation through health benefits, reuse products as well as reduce ecological impacts. In the literature there seems to be no compilation of a wide range of available onsite sanitation systems around the world that encompasses black and greywater treatment plus stand-alone dry and urine separation toilet systems. Seventy technologies have been identified and classified according to the different waste source streams. Sub-classification based on major treatment methods included aerobic digestion, composting and vermicomposting, anaerobic digestion, sand/soil/peat filtration and constructed wetlands. Potential users or suppliers of sanitation systems can choose from wide range of technologies available and examine the different treatment principles used in the technologies. Sanitation systems need to be selected according to the local social, economic and environmental conditions and should aim to be sustainable.

  9. Small Hydropower in Nigeria

    Institute of Scientific and Technical Information of China (English)



    Nigeria is the most populaous black nation in the world. It has an area of 913,072 square kilometres. The country population is about 120 million. There are three major languages, Hausa, Yoruba and Igbo, although there is still more than 380 dialects in local languages. There are large number of household on the African continent that are unelectrified.In Nigeria about 70 million people remain literally in the dark without access to electricity. The majority of these numbers are in the rural areas. This workshop is apt in a number of ways. It is a joint effort between government, private sector, the academic and other practitioners in small hydro power station, it is also a promotion of business and industrial activities as well as development of renewable energy resources. I wish to commend the organizers of this workshop. The focus of the workshop is relevant to the agenda of the Federal Ministry of Power and Steel and aspirations of the Federal Government of Nigeria to provide regular and steady electricity to majority of Nigerians before the end of year 2001.

  10. Improved technical specifications

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.R.


    Improved technical specifications for nuclear power plants are outlined. The objectives of this work are to improve safety, provide a clearer understanding of safety significance, and ease NRC and industry administrative burdens. Line item improvements, bases, and implementation of the specifications are discussed.

  11. 48 CFR 970.1907 - Subcontracting with Small Business, Small Disadvantaged Business and Woman-Owned Small Business... (United States)


    ... Business, Small Disadvantaged Business and Woman-Owned Small Business Concerns. 970.1907 Section 970.1907... MANAGEMENT AND OPERATING CONTRACTS Small, Small Disadvantaged and Women-Owned Small Business Concerns 970.1907 Subcontracting with Small Business, Small Disadvantaged Business and Woman-Owned Small...

  12. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn


    An increased interest in the notion of place has evolved in interaction design based on the proliferation of wireless infrastructures, developments in digital media, and a ‘spatial turn’ in computing. In this article, place-specific computing is suggested as a genre of interaction design...... that addresses the shaping of interactions among people, place-specific resources and global socio-technical networks, mediated by digital technology, and influenced by the structuring conditions of place. The theoretical grounding for place-specific computing is located in the meeting between conceptions...... examples of place-specific computing are presented from a series of pilot studies, conducted in close collaboration with design students in Malmö, Berlin, Cape Town and Rome, that generated 36 design concepts in the genre. Reflecting on these examples, issues in the design of place-specific computing...

  13. Small Thermophotovoltaic Prototype Systems (United States)

    Durisch, Wilhelm; Bitnar, Bernd; von Roth, Fritz; Palfinger, Günther


    In an earlier paper [1], we reported on a small grid-connected thermophotovoltaic (TPV) system consisting of an ytterbia mantle emitter and silicon solar cells with 16 % efficiency (under solar irradiance at Standard Test Conditions, STC). The emitter was heated up using a butane burner with a rated thermal power of 1.35 kW (referring to the lower heating value). This system produced an electrical output of 15 W, which corresponds to a thermal to electric (direct current) conversion efficiency of 1.1 %. In the interim, further progress has been made, and significantly higher efficiencies have been achieved. The most important development steps are: 1) The infrared radiation-absorbing water filter between emitter and silicon cells (to protect the cells against overheating and against contact with flue gasses) has been replaced by a suitable glass tube. By doing this, it has been possible to prevent losses of convertible radiation in water. 2) Cell cooling has been significantly improved, in order to reduce cell temperature, and therefore increase conversion efficiency. 3) The shape of the emitter has been changed from spherical to a quasi-cylindrical geometry, in order to obtain a more homogeneous irradiation of the cells. 4) The metallic burner tube, on which the ytterbia emitter was fixed in the initial prototypes, has been replaced by a heat-resistant metallic rod, carrying ceramic discs as emitter holders. This has prevented the oxidation and clogging of the perforated burner tube. 5) Larger reflectors have been used to reduce losses in useful infrared radiation. 6) Smaller cells have been used, to reduce electrical series resistance losses. Applying all these improvements to the basic 1.35 kW prototype, we attained a system efficiency of 1.5 %. By using preheated air for combustion (at approximately 370 °C), 1.8 % was achieved. In a subsequent step, a photocell generator was constructed, consisting of high-efficiency silicon cells (21% STC efficiency). In this

  14. Small Mercury Relativity Orbiter (United States)

    Bender, Peter L.; Vincent, Mark A.


    The accuracy of solar system tests of gravitational theory could be very much improved by range and Doppler measurements to a Small Mercury Relativity Orbiter. A nearly circular orbit at roughly 2400 km altitude is assumed in order to minimize problems with orbit determination and thermal radiation from the surface. The spacecraft is spin-stabilized and has a 30 cm diameter de-spun antenna. With K-band and X-band ranging systems using a 50 MHz offset sidetone at K-band, a range accuracy of 3 cm appears to be realistically achievable. The estimated spacecraft mass is 50 kg. A consider-covariance analysis was performed to determine how well the Earth-Mercury distance as a function of time could be determined with such a Relativity Orbiter. The minimum data set is assumed to be 40 independent 8-hour arcs of tracking data at selected times during a two year period. The gravity field of Mercury up through degree and order 10 is solved for, along with the initial conditions for each arc and the Earth-Mercury distance at the center of each arc. The considered parameters include the gravity field parameters of degree 11 and 12 plus the tracking station coordinates, the tropospheric delay, and two parameters in a crude radiation pressure model. The conclusion is that the Earth-Mercury distance can be determined to 6 cm accuracy or better. From a modified worst-case analysis, this would lead to roughly 2 orders of magnitude improvement in the knowledge of the precession of perihelion, the relativistic time delay, and the possible change in the gravitational constant with time.

  15. Small 'l' leadership. (United States)

    Parsons, Jenni


    Recently I attended the RACGP Leadership Masterclass in Sydney. When I enrolled, I thought, 'Yes... sounds interesting...good speakers... I need to learn something about leadership...'As the time drew closer I started to get a bit anxious about the whole thing. I realised that the title, 'Masterclass', probably implied that the attendees were expected to already know something about leadership and its theories, if not have considerable expertise and experience in leadership. I also wondered how the workshop sessions were going to go and I started to feel a bit sorry for the facilitators. Imagine trying to facilitate a group of 10 aspiring leaders... a bit like trying to herd cats. A few days later I received a call from the organisers,saying they were a bit short of facilitators and could I help out if necessary. Great... better do a crash course in cat herding! Then there was the first 'predisposing activity'. Step 1: think of leaders you admire. Easy enough. Leaders of social justice and social change on a world stage, people who have shown great courage of their convictions and great orators popped into my head... Ghandi, Martin Luther King, Mandela, JFK. Step 2:describe the ways in which you are like these leaders. Whoa!Never going to measure up here. I wondered if there was going to be sessions on 'leadership for introverts', or 'leadership of small things', or 'leaders without grand vision or fabulous oratory skills', or perhaps 'leadership for people who are deeply suspicious of the corrupting influence of power'.

  16. Small diameter carbon nanopipettes (United States)

    Singhal, Riju; Bhattacharyya, Sayan; Orynbayeva, Zulfiya; Vitol, Elina; Friedman, Gary; Gogotsi, Yury


    Nanoscale multifunctional carbon probes facilitate cellular studies due to their small size, which makes it possible to interrogate organelles within living cells in a minimally invasive fashion. However, connecting nanotubes to macroscopic devices and constructing an integrated system for the purpose of fluid and electrical signal transfer is challenging, as is often the case with nanoscale components. We describe a non-catalytic chemical vapor deposition based method for batch fabrication of integrated multifunctional carbon nanopipettes (CNPs) with tip diameters much smaller (10-30 nm) than previously reported (200 nm and above) and approaching those observed for multiwalled carbon nanotubes. This eliminates the need for complicated attachment/assembly of nanotubes into nanofluidic devices. Variable tip geometries and structures were obtained by controlled deposition of carbon inside and outside quartz pipettes. We have shown that the capillary length and gas flow rate have a marked effect on the carbon deposition. This gives us a flexible protocol, useful for growing carbon layers of different thicknesses at selective locations on a glass pipette to yield a large variety of cellular probes in bulk quantities. The CNPs possess an open channel for fluid transfer with the carbon deposited inside at 875 °C behaving like an amorphous semiconductor. Vacuum annealing of the CNP tips at temperatures up to 2000 °C yields graphitic carbon structures with an increase in conductivity of two orders of magnitude. Penetration of the integrated carbon nanoprobes into cells was shown to produce minimal Ca2+ signals, fast recovery of basal Ca2+ levels and no adverse activation of the cellular metabolism during interrogation times as long as 0.5-1 h.

  17. Regular Small-World Network

    Institute of Scientific and Technical Information of China (English)

    ZOU Zhi-Yun; MAO Bao-Hua; HAO Hai-Ming; GAO Jian-Zhi; YANG Jie-Jiao


    According to the deficiencies in Watts and Strogatz's small-world network model, we present a new regular model to establish the small-world network. Besides the property of the small-world, this model has other properties such as accuracy in controlling the average shortest path length L, and the average clustering coefficient C, also regular network topology as well as enhanced network robustness. This method improves the construction of the small-world network essentially, so that the regular small-world network closely resembles the actual network. We also present studies on the relationships among the quantities of a variety of edges, L and C in regular small-world network in detail. This research lays the foundation for the establishment of the regular small-world network and acts as a good guidance for further research of this model and its applications.

  18. Distinct management issues with Crohn's disease of the small intestine. (United States)

    Fong, Steven C M; Irving, Peter M


    Small bowel Crohn's disease can present with clinical challenges that are specific to its location. In this review, we address some of the areas that present particular problems in small bowel Crohn's disease. A key issue specific to small bowel Crohn's disease relates to its diagnosis given that access to the small bowel is limited. Radiological advances, particularly in small bowel ultrasonography and MRI, as well as the introduction of capsule endoscopy and balloon enteroscopy are helping to address this. In addition, our ability to differentiate small bowel Crohn's disease from other causes of inflammation, such as tuberculosis, is improving on the basis of better understanding of the features that differentiate these conditions. It is also becoming apparent that jejunal Crohn's disease represents a distinct disease phenotype with potentially worse clinical outcomes. Finally, because it is a rare complication, our understanding of small bowel cancer associated with Crohn's disease remains limited. Recent publications are, however, starting to improve our knowledge of this condition. Although small bowel Crohn's disease presents specific management issues not seen in patients with Crohn's disease elsewhere in the gastrointestinal tract, our knowledge of how to manage these is improving.

  19. 77 FR 30227 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small... (United States)


    ... (SBIR) Program and Small Business Technology Transfer (STTR) Program AGENCY: U.S. Small Business... (SBIR) and Small Business Technology Transfer (STTR) Programs. The proposed rule would implement... technological constraints, participation is limited to 125 registrants for the Webinar. If demand...

  20. Microdischarge plasma thrusters for small satellite propulsion (United States)

    Raja, Laxminarayan


    Small satellites weighing less than 100 kg are gaining importance in the defense and commercial satellite community owing to advantages of low costs to build and operate, simplicity of design, rapid integration and testing, formation flying, and multi-vehicle operations. The principal challenge in the design and development of small satellite subsystems is the severe mass, volume, and power constraints posed by the overall size of the satellite. The propulsion system in particular is hard to down scale and as such poses a major stumbling block for small satellite technology. Microdischarge-based miniaturized plasma thrusters are potentially a novel solution to this problem. In its most basic form a microdischarge plasma thruster is a simple extension of a cold gas micronozzle propulsion device, where a direct or alternating current microdischarge is used to preheat the gas stream to improve to specific impulse of the device. We study a prototypical thruster device using a detailed, self-consistent coupled plasma and fluid flow computational model. The model describes the microdischarge power deposition, plasma dynamics, gas-phase chemical kinetics, coupling of the plasma phenomena with high-speed flow, and overall propulsion system performance. Unique computational challenges associated with microdischarge modeling in the presence of high-speed flows are addressed. Compared to a cold gas micronozzle, a significant increase in specific impulse (50 to 100 %) is obtained from the power deposition in the diverging supersonic section of the thruster nozzle. The microdischarge remains mostly confined inside the micronozzle and operates in an abnormal glow discharge regime. Gas heating, primarily due to ion Joule heating, is found to have a strong influence on the overall discharge behavior. The study provides a validation of the concept as simple and effective approach to realizing a relatively high-specific impulse thruster device at small geometric scales.

  1. Targeting Th17 Cells with Small Molecules and Small Interference RNA. (United States)

    Lin, Hui; Song, Pingfang; Zhao, Yi; Xue, Li-Jia; Liu, Yi; Chu, Cong-Qiu


    T helper 17 (Th17) cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL-) 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA) and Crohn's disease. Alternative agents targeting Th17 cells may be a better way to inhibit the development and function of Th17 cells than antibodies of blocking a single effector cytokine. Retinoic acid-related orphan receptor gamma t (RORγt) which acts as the master transcription factor of Th17 differentiation has been an attractive pharmacologic target for the treatment of Th17-mediated autoimmune disease. Recent progress in technology of chemical screen and engineering nucleic acid enable two new classes of therapeutics targeting RORγt. Chemical screen technology identified several small molecule specific inhibitors of RORγt from a small molecule library. Systematic evolution of ligands by exponential enrichment (SELEX) technology enabled target specific aptamers to be isolated from a random sequence oligonucleotide library. In this review, we highlight the development and therapeutic potential of small molecules inhibiting Th17 cells by targeting RORγt and aptamer mediated CD4(+) T cell specific delivery of small interference RNA against RORγt gene expression to inhibit pathogenic effector functions of Th17 lineage.

  2. Targeting Th17 Cells with Small Molecules and Small Interference RNA

    Directory of Open Access Journals (Sweden)

    Hui Lin


    Full Text Available T helper 17 (Th17 cells play a central role in inflammatory and autoimmune diseases via the production of proinflammatory cytokines interleukin- (IL- 17, IL-17F, and IL-22. Anti-IL-17 monoclonal antibodies show potent efficacy in psoriasis but poor effect in rheumatoid arthritis (RA and Crohn’s disease. Alternative agents targeting Th17 cells may be a better way to inhibit the development and function of Th17 cells than antibodies of blocking a single effector cytokine. Retinoic acid-related orphan receptor gamma t (RORγt which acts as the master transcription factor of Th17 differentiation has been an attractive pharmacologic target for the treatment of Th17-mediated autoimmune disease. Recent progress in technology of chemical screen and engineering nucleic acid enable two new classes of therapeutics targeting RORγt. Chemical screen technology identified several small molecule specific inhibitors of RORγt from a small molecule library. Systematic evolution of ligands by exponential enrichment (SELEX technology enabled target specific aptamers to be isolated from a random sequence oligonucleotide library. In this review, we highlight the development and therapeutic potential of small molecules inhibiting Th17 cells by targeting RORγt and aptamer mediated CD4+ T cell specific delivery of small interference RNA against RORγt gene expression to inhibit pathogenic effector functions of Th17 lineage.

  3. Analysis of Small Intestinal Microbiome in Children with Autism (United States)


    overgrowth of specific populations of bacteria and analyze the relationship between the intestinal flora and behavior. Our current sub-contractor...determine if there is an overgrowth of specific populations of bacteria and analyze the relationship between the intestinal flora and behavior. In aim 1, we...AD_________________ Award Number: W81XWH-10-1-0477 TITLE: Analysis of Small Intestinal Microbiome


    Institute of Scientific and Technical Information of China (English)

    Boubacar KANE; Pierre Y.JULIEN


    An extensive database of reservoir sedimentation surveys throughout continental United States is compiled and analyzed to determine specific degradation SD relationships as function of mean annual rainfall R, drainage area A, and watershed slope S. The database contains 1463 field measurements and specific degradation relationships are defined as function of A, R and S. Weak trends and significant variability in the data are noticeable. Specific degradation measurements are log normally distributed with respect to R, A, and S and 95% confidence intervals are determined accordingly. The accuracy of the predictions does not significantly increase as more independent variables are added to the regression analyses.

  5. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald


    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  6. Small Bowel Hamartoma: A Huge Diverticulum of Small Bowel

    Directory of Open Access Journals (Sweden)

    Hamdi Ebdewi


    Full Text Available A-20-year old male, with no significant medical history, presented with clinical features mimicking a perforated acute appendicitis. Because of features of peritonitis, a laparotomy was performed which showed a segment of small bowel with multiple large diverticula and mesenteric cysts. A segmental small bowel resection was performed. The patient made an uneventful recovery from surgery. Histology revealed features of a small bowel hamartoma.

  7. Jupiter small satellite montage (United States)


    A montage of images of the small inner moons of Jupiter from the camera onboard NASA's Galileo spacecraft shows the best views obtained of these moons during Galileo's 11th orbit around the giant planet in November 1997. At that point, Galileo was completing its first two years in Jupiter orbit--known as the Galileo 'prime mission'--and was about to embark on a successful two-year extension, called the Galileo Europa Mission. The top two images show the moon Thebe. Thebe rotates by approximately 50 degrees between the time these two images were taken, so that the same prominent impact crater is seen in both views; this crater, which has been given the provisional name Zethus, is near the point on Thebe that faces permanently away from Jupiter. The next two images show the moon Amalthea; they were taken with the Sun directly behind the observer, an alignment that emphasizes patterns of intrinsically bright or dark surface material. The third image from the top is a view of Amalthea's leading side, the side of the moon that 'leads' as Amalthea moves in its orbit around Jupiter. This image looks 'noisy' because it was obtained serendipitously during an observation of the Jovian satellite Io (Amalthea and Io shared the same camera frame but the image was exposed for bright Io rather than for the much darker Amalthea). The fourth image from the top emphasizes prominent 'spots' of relatively bright material that are located near the point on Amalthea that faces permanently away from Jupiter. The bottom image is a view of the tiny moon Metis. In all the images, north is approximately up, and the moons are shown in their correct relative sizes. The images are, from top to bottom: Thebe taken on November 7, 1997 at a range of 504,000 kilometers (about 313,000 miles); Thebe on November 7, 1997 at a range of 548,000 kilometers (about 340,000 miles); Amalthea on November 6, 1997 at a range of about 650,000 kilometers (about 404,000 miles); Amalthea on November 7, 1997 at a

  8. [Traveling with small children]. (United States)

    Olivier, C


    Traveling with children especially in the tropics requires special planning. Contraindications are rare but care providers should obtain information about medical and transfusional facilities at the destination. Children should receive all vaccinations required for international travel and for specific countries, taking into account age, location, duration of stay, and purpose of trip. A first aid kit should be packed containing a thermometer, bandages, antiseptic agents, a total sunscreen preparation, a mosquito net, sterile compresses, tablets for water disinfection, and indispensable medications (antimalarial agents, antipyretics, oral rehydration solutions, antiemetics, and eye wash). The main indication for chemoprophylaxis is malaria. Chloroquine is recommended for most locations but proguanil may be necessary in areas of resistance. Special attention must be paid to skin care in infants: maintaining cleanliness, avoiding cuts insofar as possible, and treating any wounds. Clothing must be carefully laundered and adequate to prevent overexposure to sunlight and insect bites. Insect bites must also be prevented by applying repellents, using mosquito nets, and wearing insecticide-treated garments. Handwashing by people who prepare meals and by the children before eating is important to prevent food poisoning. Breast feeding is advisable for infants. Thorough cooking of meats, rinsing of fresh produce, drinking of bottled beverages, and sterilization of water are also important food safety measures. These precautions are usually adequate to allow safe travel with children.

  9. Small Business Innovation Research and Small Business Technology Transfer Programs (United States)

    Garrison, Lynn; Jasper, Gwen


    The Small Business Innovation Research (SBIR)/Small Business Technology Transfer (STTR) programs fund the research, development, and demonstration of innovative technologies that fulfill NASA's needs as described in the annual Solicitations and have significant potential for successful commercialization. The only eligible participants are small business concern (SBC) with 500 or fewer employees or a nonprofit research institute such as a university or a research laboratory with ties to an SBC. These programs are potential sources of seed funding for the development of small business innovations.

  10. The Learning Design Specification

    NARCIS (Netherlands)

    Olivier, Bill; Tattersall, Colin


    Olivier, B. & Tattersall, C. (2005). The Learning Design Specification In: Koper, R. & Tattersall, C., Learning Design: A Handbook on Modelling and Delivering Networked Education and Training (pp. 21-40). Berlin-Heidelberg: Springer Verlag.

  11. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn; Johansson, Michael

    An increased interest in the notion of place has evolved in interaction design. Proliferation of wireless infrastructure, developments in digital media, and a ‘spatial turn’ in computing provides the base for place-specific computing as a suggested new genre of interaction design. In the REcult...... project place- specific computing is explored through design oriented research. This article reports six pilot studies where design students have designed concepts for place-specific computing in Berlin (Germany), Cape Town (South Africa), Rome (Italy) and Malmö (Sweden). Background and arguments...... for place-specific computing as a genre of interaction design are described. A total number of 36 design concepts designed for 16 designated zones in the four cities are presented. An analysis of the design concepts is presented indicating potentials, possibilities and problems as directions for future...

  12. The Learning Design Specification

    NARCIS (Netherlands)

    Olivier, Bill; Tattersall, Colin


    Olivier, B. & Tattersall, C. (2005). The Learning Design Specification In: Koper, R. & Tattersall, C., Learning Design: A Handbook on Modelling and Delivering Networked Education and Training (pp. 21-40). Berlin-Heidelberg: Springer Verlag.

  13. Ontology Requirements Specification


    Suárez-Figueroa, Mari Carmen; Gómez-Pérez, A.


    The goal of the ontology requirements specification activity is to state why the ontology is being built, what its intended uses are, who the end users are, and which requirements the ontology should fulfill. This chapter presents detailed methodological guidelines for specifying ontology requirements efficiently. These guidelines will help ontology engineers to capture ontology requirements and produce the ontology requirements specification document (ORSD). The ORSD will play a key role dur...

  14. Small Wind Site Assessment Guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Tim [Advanced Energy Systems LLC, Eugene, OR (United States); Preus, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States)


    Site assessment for small wind energy systems is one of the key factors in the successful installation, operation, and performance of a small wind turbine. A proper site assessment is a difficult process that includes wind resource assessment and the evaluation of site characteristics. These guidelines address many of the relevant parts of a site assessment with an emphasis on wind resource assessment, using methods other than on-site data collection and creating a small wind site assessment report.

  15. Investigation on a Small Oscillogram

    Institute of Scientific and Technical Information of China (English)


    A small oscillogram, one end of which was substituted by a bright point caused by the redox of an appropriate depolarizer and the other end of which was the redox of Hg or the redox of supporting electrolyte cation, was investigated in this paper. Experimental results of application of the small oscillogram to oscillographic determination of cefoperazone showed that the small oscillogram was more stable, sensitive, and less interference than classical oscillogram.

  16. Insights into the classification of small GTPases

    Directory of Open Access Journals (Sweden)

    Dominik Heider


    Full Text Available Dominik Heider1, Sascha Hauke3, Martin Pyka4, Daniel Kessler21Department of Bioinformatics, Center for Medical Biotechnology, 2Institute of Cell Biology (Cancer Research, University of Duisburg-Essen, Essen, Germany; 3Institute of Computer Science, University of Münster, Münster, Germany; 4Interdisciplinary Center for Clinical Research, University Hospital of Münster, Münster, GermanyAbstract: In this study we used a Random Forest-based approach for an assignment of small guanosine triphosphate proteins (GTPases to specific subgroups. Small GTPases represent an important functional group of proteins that serve as molecular switches in a wide range of fundamental cellular processes, including intracellular transport, movement and signaling events. These proteins have further gained a special emphasis in cancer research, because within the last decades a huge variety of small GTPases from different subgroups could be related to the development of all types of tumors. Using a random forest approach, we were able to identify the most important amino acid positions for the classification process within the small GTPases superfamily and its subgroups. These positions are in line with the results of earlier studies and have been shown to be the essential elements for the different functionalities of the GTPase families. Furthermore, we provide an accurate and reliable software tool (GTPasePred to identify potential novel GTPases and demonstrate its application to genome sequences.Keywords: cancer, machine learning, classification, Random Forests, proteins

  17. Formation and evolution of Pluto's small satellites

    CERN Document Server

    Walsh, Kevin J


    Pluto's system of 5 known satellites are in a puzzling orbital configuration. Each of the four small satellites are on low-eccentricity and low-inclination orbits situated near a mean motion resonance with the largest satellite Charon. The Pluto-Charon binary likely formed as a result of a giant impact and so the simplest explanation for the small satellites is that they accreted from debris of that collision. The Pluto-Charon binary has evolved outward since its formation due to tidal forces, which drove them into their current doubly synchronous state. Meanwhile, leftover debris from the formation of Charon was not initially distant enough from Pluto-Charon to explain the orbits of the current small satellites. The outstanding problems of the system are the movement of debris outward and the small satellites location near mean motion resonances with Charon. This work explores the dynamical behavior of collisionally interacting debris orbiting the Pluto-Charon system. While this work specifically tests initi...

  18. p40、天门冬氨酸蛋白酶、甲状腺转录因子-1在肺鳞癌与腺癌表达敏感性和特异性%p40、Napsin-A and TTF-1 ---the specific immunohistochemical mark to identify squamous cell carcinoma and adenocarcinoma of non-small cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)



    Objective:To study the significant immunohistochemical mark to identifiy squamous cell carcinoma and adenocarcinoma of non-small cell lung cancer. Methods:The expression of p63, p40, CK5/6, TTF-1, CK7 and Napsin-A was detected in 51 cases with non-small cell lung cancer by using immunohistochemistry of SP. Results:In 51 cases with non-small cell lung cancer, there were 20 cases with squamous cell carcinoma and 31 cases with adenocarcinoma. The positive expression rates of p63,p40 and CK5/6 in lung squamous cell carcinoma was 100%(20/20), 95%(19/20) and 90%(18/20)respectively ; the sensitivity of p63, p40 and CK5/6 was similar (P=0.355),but the specificity of p40 was higher than that of p63 and CK5/6(P=0.040). The positive expression rate of TTF-1, CK7 and Napsin-A in lung adenocarcino-ma was 87.1%(27/31), 80.6%(25/31) and 90.3%(28/31)respectively, the sensitivity of TTF-1,CK7 and Napsin-A was similar, too(P=0.538). The specificity of TTF-1、Napsin-A was higher than that of CK7(P=0.002). Conclusion:The sensi-tivity of p40, Napsin-A and TTF-1 is higher in non-small cell lung cancer, and they are the specific marks to identify squamous cell carcinoma and adenocarcinoma in the lungs. Detection of p40, Napsin-A and TTF-1 together can be more accurate in differential diagnosis of non-small cell lung cancer and provides a theoretical basis for clinical treatment.%目的:探讨肺非小细胞癌组织中鉴别鳞癌和腺癌有意义的免疫组化检测标记。方法:采用免疫组织化学SP法检测非小细胞肺癌51例组织中p63、p40、CK5/6、甲状腺转录因子-1(TTF-1)、CK7、天门冬氨酸蛋白酶(Napsin-A)的表达。结果:(1)p40、p63、CK5/6在非小细胞肺癌中表达:非小细胞肺癌51例中,p40、p63、CK5/6在鳞状细胞癌20例中阳性表达为20例(100.0%),19例(95.0%),18例(90.0%),在腺癌31例组织中阳性表达为0例(0.0%)、6例(19.4%)、3例(9.7%)。p40在31例腺癌中无1

  19. DOE small scale fuel alcohol plant design

    Energy Technology Data Exchange (ETDEWEB)

    LaRue, D.M.; Richardson, J.G.


    The Department of Energy, in an effort to facilitate the deployment of rural-based ethanol production capability, has undertaken this effort to develop a basic small-scale plant design capable of producing anhydrous ethanol. The design, when completed, will contain all necessary specifications and diagrams sufficient for the construction of a plant. The design concept is modular; that is, sections of the plant can stand alone or be integrated into other designs with comparable throughput rates. The plant design will be easily scaled up or down from the designed flow rate of 25 gallons of ethanol per hour. Conversion factors will be provided with the final design package to explain scale-up and scale-down procedures. The intent of this program is to provide potential small-scale producers with sound information about the size, engineering requirements, costs and level of effort in building such a system.

  20. Domain-Specific Multimodeling

    DEFF Research Database (Denmark)

    Hessellund, Anders

    Enterprise systems are complex artifacts. They are hard to build, manage, understand, and evolve. Existing software development paradigms fail to properly address challenges such as system size, domain complexity, and software evolution when development is scaled to enterprise systems. We propose...... domain-specific multimodeling as a development paradigm to tackle these challenges in a language-oriented manner. The different concerns of a system are conceptually separated and made explicit as independent domain-specific languages. This approach increases productivity and quality by raising...... the overall level of abstraction. It does, however, also introduce a new problem of coordinating multiple different languages in a single system. We call this problem the coordination problem. In this thesis, we present the coordination method for domain-specific multimodeling that explicitly targets...

  1. Advances in molecular imaging of prostate cancer targeting prostate specific membrane antigen with small molecular radionuclide probes%以核素标记前列腺特异性膜抗原小分子抑制剂为探针的前列腺癌分子影像研究进展

    Institute of Scientific and Technical Information of China (English)

    胡四龙(综述); 许晓平; 章英剑(审校)


    Prostate speciifc membrane antigen (PSMA) is expressed in normal prostate epithelial cells and strongly up regulated in initial and advanced prostate carcinoma. Therefore, PSMA is an attractive molecular target for the detection of primary and metastatic lesions. It plays an important role in the diagnosis, staging, prognostic evaluation and targeted treatment in prostate carcinoma patients. This review will summarize the progress of small molecular radionuclide probes, which targeted PSMA, for visualizing prostate cancer.%前列腺特异性膜抗原(PSMA)高表达于前列腺癌及其转移灶中,可作为生物分子靶点,在前列腺癌的早期诊断、分期、复发检测、预后判断及靶向治疗中具有重要价值。本文重点综述以核素标记PSMA小分子抑制剂为探针的前列腺癌分子影像研究进展。

  2. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

     This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....... This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....

  3. Cockpit management and Specific Behavioral Objectives (SBOs) (United States)

    Mudge, R. W.


    One of the primary tools used to accomplish the task of effective training is the specific behavioral objective (SBO). An SBO is simply a statement which specifically identifies a small segment of the final behavior sought, and a little more. The key word is specific. The company pinpoints exactly what it is it wants the pilot to do after completing training, and what it should evaluate from the point of view of both the program and the pilot. It tells the junior crewmember exactly, specifically, what he should monitor and support insofar as the management function is concerned. It gives greater meaning to the term second in command. And finally, it tells the supervisory pilot exactly what he should observe, evaluate, and instruct, insofar as the management function is concerned.

  4. Financial management for small companies (United States)

    Bruce Hansen; Jeff Palmer; Jeff Palmer


    The wood-products industry is characterized by many small manufacturers that lack the staff to compile and analyze information on their operations and investments. Two computer programs, FRAN and JEFFI, have been developed by the USDA Forest Service at Princeton, West Virginia,to help small companies better analyze and monitor current performance, and better evaluate...

  5. Introduction: innovation and small business

    NARCIS (Netherlands)

    A.R. Thurik (Roy)


    textabstractThis paper introduces the special issue of Small Business Economics on Innovation. What binds the papers together is either their focus on the effect of firm size on the causes and consequences of innovation or their focus on the role small firms play in reshaping the industrial landscap


    National Research Council Canada - National Science Library

    Rodrigues, Tonny Kerley de Alencar; Lira, Átila De Melo; Naas, Irenilza De Alencar


    .... And the data confirms that small Brazilian companies generally have difficulties to sell their innovations. Keywords: innovation, small enterprises, patents. 1. INTRODUCTION Companies worldwide are looking to technological innovation as feasible for your market expansion (BURNS; STALKER, 1961; NELSON, 1993) alternative. In Brazil, the change an...

  7. Small Molecular as SIRT Modulators. (United States)

    Yao, Lei; Xu, Xiangming; Chen, Kai


    Sirtuins are class III histone deacetylases, they involve in many important biological functions. Small molecules that can modulate sirtuin activity have been shown to have potential for treating many human diseases. In the article, recent development of small molecular as SIRT modulators has been reviewed.

  8. Standard Deviation for Small Samples (United States)

    Joarder, Anwar H.; Latif, Raja M.


    Neater representations for variance are given for small sample sizes, especially for 3 and 4. With these representations, variance can be calculated without a calculator if sample sizes are small and observations are integers, and an upper bound for the standard deviation is immediate. Accessible proofs of lower and upper bounds are presented for…

  9. Small Bowel Review - Part I


    ABR Thomson; Wild, G.


    Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleoside...

  10. Introduction: innovation and small business

    NARCIS (Netherlands)

    A.R. Thurik (Roy)


    textabstractThis paper introduces the special issue of Small Business Economics on Innovation. What binds the papers together is either their focus on the effect of firm size on the causes and consequences of innovation or their focus on the role small firms play in reshaping the industrial


    Directory of Open Access Journals (Sweden)



    Full Text Available The Idea of approach to maintain small family norm in the family and so to the society is the hope for almost all of the couples as the saying -"Small family is a happy family". And every couple always thinks and plan for a safer and better future.





    The Idea of approach to maintain small family norm in the family and so to the society is the hope for almost all of the couples as the saying -"Small family is a happy family". And every couple always thinks and plan for a safer and better future.

  13. How Small Is a Billionth? (United States)

    Gough, John


    Children's natural curiosity about numbers, big and small can lead to exploring place-value ideas. But how can these abstract concepts be experienced more concretely? This article presents some practical approaches for conceptualising very small numbers using linear models, area models, volume models, and diagrams.

  14. Resourcing Change in Small Schools (United States)

    Anderson, Michelle; White, Simone


    The theme of this article is the challenge that school leaders face in creating the conditions for learning in small schools. We draw on the concepts of "social capital" and "social entrepreneurship" to identify tensions and possibilities for school leaders in a case study of a small rural school as they seek to find resources…

  15. Specification of Learning Content Using Feature Diagrams (United States)

    Damaševičius, Robertas

    The main idea of a learning object (LO) is to break educational content down into small chunks that can be reused in various learning environments. When reused, such small chunks of educational content are combined in various ways leading to a great variability of the learning content. We propose using feature diagrams (FDs) for the specification of learning content at different layers of abstraction starting from the organization of teaching material in a lecture down to the specification and demonstration of particular software/hardware components. FDs can be used by (1) designers, teachers, and learners for graphical representation of domain knowledge in LOs; (2) programmers to specify and express variability-commonality relationships of LOs at a higher abstraction level to allow the development and implementation of generative LOs; and (3) researchers as a vehicle for analysis and better understanding of the e-Learning domain itself.

  16. Small bowel obstruction- a surprise. (United States)

    Mathew, Jeffrey Daniel; Cp, Ganesh Babu; M, Balachandar; M, Ramanathan


    Trans - omental hernia is very rare, accounting to 1-4% of all internal hernias which is an unusual cause of small bowel obstruction. Here we present a case report of a small bowel obstruction in a female due to trans - omental hernia presenting with central abdominal pain, distension and bilious vomiting. She had no previous history of trauma, surgery. Plain X-ray abdomen erect showed multiple air fluid levels with dilated small bowel loops. Emergency laparotomy revealed a segment of congested small bowel loop (ileum) through a defect in greater omentum. On table the herniated bowel loop was reduced and the defect in greater omentum was closed primarily. There was no necessity for bowel resection as it regained normal colour after reduction. Postoperative period was uneventful with complete resolution of symptoms. This case is presented for its rarity and its importance in clinical differential diagnosis of acute abdomen due to small bowel obstruction.

  17. Small Luggage for a Long Journey: Transfer of Vesicle-Enclosed Small RNA in Interspecies Communication (United States)

    Lefebvre, Fabio A.; Lécuyer, Eric


    In the evolutionary arms race, symbionts have evolved means to modulate each other's physiology, oftentimes through the dissemination of biological signals. Beyond small molecules and proteins, recent evidence shows that small RNA molecules are transferred between organisms and transmit functional RNA interference signals across biological species. However, the mechanisms through which specific RNAs involved in cross-species communication are sorted for secretion and protected from degradation in the environment remain largely enigmatic. Over the last decade, extracellular vesicles have emerged as prominent vehicles of biological signals. They can stabilize specific RNA transcripts in biological fluids and selectively deliver them to recipient cells. Here, we review examples of small RNA transfers between plants and bacterial, fungal, and animal symbionts. We also discuss the transmission of RNA interference signals from intestinal cells to populations of the gut microbiota, along with its roles in intestinal homeostasis. We suggest that extracellular vesicles may contribute to inter-species crosstalk mediated by small RNA. We review the mechanisms of RNA sorting to extracellular vesicles and evaluate their relevance in cross-species communication by discussing conservation, stability, stoichiometry, and co-occurrence of vesicles with alternative communication vehicles. PMID:28360889

  18. Site-Specific Innovation

    DEFF Research Database (Denmark)

    Reeh, Henrik; Hemmersam, Peter


    , but also places for emerging lifestyles and cultural processes. In this transformation process, harbours provide arenas for a new urban dynamics, involving multiple sectors and functions in society, as opposed to the monoculturalism prevailing in the ages of the industrial city. To us, the critical...... question is how innovation may contribute to urban life and site-specific qualities....

  19. Acquiring specific interpreting competence

    Directory of Open Access Journals (Sweden)

    Jana Zidar Forte


    Full Text Available In postgraduate interpreter training, the main objective of the course is to help trainees develop various competences, from linguistic, textual and cultural competence, to professional and specific interpreting competence. For simultaneous interpreting (SI, the main focus is on mastering the SI technique and strategies as well as on developing and strengthening communicative skills, which is discussed and illustrated with examples in the present paper. First, a brief overview is given of all the necessary competences of a professional interpreter with greater emphasis on specific interpreting competence for SI. In the second part of the paper, various approaches are described in terms of acquiring specific skills and strategies, specifically through a range of exercises. Besides interpreting entire speeches, practical courses should also consist of targeted exercises, which help trainees develop suitable coping strategies and mechanisms (later on almost automatisms, while at the same time "force" them to reflect on their individual learning process and interpreting performance. This provides a solid base on which trained interpreters can progress and develop their skills also after joining the professional sphere.

  20. Site-Specific Innovation

    DEFF Research Database (Denmark)

    Reeh, Henrik; Hemmersam, Peter


    Currently, cities across the Northern European region are actively redeveloping their former industrial harbours. Indeed, harbours areas are essential in the long-term transition from industrial to information and experience societies; harbours are becoming sites for new businesses and residences...... question is how innovation may contribute to urban life and site-specific qualities....

  1. IDC System Specification Document.

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, David J.


    This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris

  2. LOCKE Detailed Specification Tables

    CERN Document Server

    Menezo, Lucia G; Gregorio, Jose-Angel


    This document shows the detailed specification of LOCKE coherence protocol for each cache controller, using a table-based technique. This representation provides clear, concise visual information yet includes sufficient detail (e.g., transient states) arguably lacking in the traditional, graphical form of state diagrams.

  3. Small is beautiful: customer driven software development

    DEFF Research Database (Denmark)

    Hansen, Henrik A.B.; Koch, Christian; Pleman, Allan


    to develop their software. In small software houses operating in markets with complex products such as ERP (enterprise resource planning) systems, networking is necessary in order to gain the needed knowledge and resources in the production development process. Network is not seen as a magic word but leads...... to different benefits and short comings for the collaborative companies depending on the specific context. In this paper we discuss three types of networks: collaboration between users and producer(s), collaboration between a software house and third party suppliers, and a collaboration between academics...

  4. Effect of anisotropy on small magnetic clusters

    CERN Document Server

    Hucht, Alfred; Sil, Shreekantha; Entel, Peter; 10.1103/PhysRevB.84.104438


    The effect of dipolar interaction and local uniaxial anisotropy on the magnetic response of small spin clusters where spins are located on the vertices of icosahedron, cuboctahedron, tetrahedron and square geometry have been investigated. We consider the ferromagnetic and antiferromagnetic spin-1/2 and spin-1 Heisenberg model with uniaxial anisotropy and dipolar interaction and apply numerical exact diagonalization technique in order to study the influence of frustration and anisotropy on the ground state properties of the spin-clusters. The ground state magnetization, spin-spin correlation and several thermodynamic quantities such as entropy and specific heat are calculated as a function of temperature and magnetic field.

  5. Children's specific fears. (United States)

    Meltzer, H; Vostanis, P; Dogra, N; Doos, L; Ford, T; Goodman, R


    Most children experience some degree of fear during their development. Specific fears are considered as an appropriate response provided that they are proportionate to the intensity of the perceived threat. Our aim is to present the prevalence of specific fears among children in the Great Britain, their socio-demographic correlates, in particular their association with ethnicity. Data on the child's experience of specific fears were obtained from parents of a national representative sample of 5- to 16-year-olds using the Development and Well-Being Assessment. Biographic, socio-demographic and socioeconomic characteristics of the child and the family were included in the questionnaire. About one-third of children were assessed by their parents as having at least one of 12 specific fears. The most commonly reported fears were animals (11.6%), blood/injections (10.8%) and the dark (6.3%). Just less than 1% of all children were assessed according to International Classification of Diseases research diagnostic criteria as having a specific phobia. Biographic, socio-demographic and socioeconomic factors were independently associated with a greater likelihood of a child having particular fears. The most marked associations were fears of the dark, loud noises, imagined supernatural beings in younger children and fear of animals among girls and all non-white groups. Although fears are only labelled as phobias when they impair functioning and interfere with life, they can cause personal distress to children and also can interfere with their daily activities. Children's fears differ in nature across different ethnic groups. Culturally mediated beliefs, values and traditions may play a role in their expression.

  6. Specificity in LSP

    Directory of Open Access Journals (Sweden)

    Thomas N. Huckin


    Full Text Available The defining feature of our field is the teaching and use of language for specific purposes. Not surprisingly, this has led to a debate over just how specific those purposes should be. The debate is longstanding, stirred initially by Hutchinson and Waters' classic 1980 article, 'ESP at the Crossroads' and reinvigorated most recently by Hyland (2002, who argues that the field has drifted away from specificity, becoming too generalized and diffuse. This paper lays out the arguments on both sides and then stakes out a position that draws from each of them. While agreeing with some of Hyland's criticisms of the 'wide-angle' position (for example, that generalized LSP can fail to appreciate the distinct linguistic and rhetorical features of specialized discourses, the paper criticizes his 'narrow-angle' position as well by pointing out that it can easily lead to a teacher-centered prescriptivism and to an overly rigid focus on certain forms and tasks at the expense of others. Furthermore, such an approach fails to prepare students for the unpredictable new forms of communication that await them in their professional careers. In general, a teachercentered approach, no matter how specific, is unlikely to have the pedagogical effectiveness of a student-centered approach, especially in heterogeneous classes. Specificity, it is argued, must ultimately be supplied by the student, not by the teacher, for it is the student more than the LSP teacher who is in the process of becoming an insider and whose interests are best served by becoming an astute analyst of the specialist discourse. The teacher's role should be that of facilitator, instructing students in analytic strategies, both rhetorical and textual. The paper concludes with a number of illustrations in how this can be done, drawing especially on work in genre study.

  7. Domain-based small molecule binding site annotation

    Directory of Open Access Journals (Sweden)

    Dumontier Michel


    Full Text Available Abstract Background Accurate small molecule binding site information for a protein can facilitate studies in drug docking, drug discovery and function prediction, but small molecule binding site protein sequence annotation is sparse. The Small Molecule Interaction Database (SMID, a database of protein domain-small molecule interactions, was created using structural data from the Protein Data Bank (PDB. More importantly it provides a means to predict small molecule binding sites on proteins with a known or unknown structure and unlike prior approaches, removes large numbers of false positive hits arising from transitive alignment errors, non-biologically significant small molecules and crystallographic conditions that overpredict ion binding sites. Description Using a set of co-crystallized protein-small molecule structures as a starting point, SMID interactions were generated by identifying protein domains that bind to small molecules, using NCBI's Reverse Position Specific BLAST (RPS-BLAST algorithm. SMID records are available for viewing at The SMID-BLAST tool provides accurate transitive annotation of small-molecule binding sites for proteins not found in the PDB. Given a protein sequence, SMID-BLAST identifies domains using RPS-BLAST and then lists potential small molecule ligands based on SMID records, as well as their aligned binding sites. A heuristic ligand score is calculated based on E-value, ligand residue identity and domain entropy to assign a level of confidence to hits found. SMID-BLAST predictions were validated against a set of 793 experimental small molecule interactions from the PDB, of which 472 (60% of predicted interactions identically matched the experimental small molecule and of these, 344 had greater than 80% of the binding site residues correctly identified. Further, we estimate that 45% of predictions which were not observed in the PDB validation set may be true positives. Conclusion By

  8. [Small cell prostatic carcinoma detected at the stage of metastases]. (United States)

    Rabii, Redouane; Meziane, Anas; Taha, Abdelatif; Joual, Abdenabi; El Mrini, Mohamed


    Small cell prostatic carcinoma is rare, with a poor prognosis. The authors report a case of small cell prostatic carcinoma in a 30-year-old patient diagnosed at the stage of metastases. Immunohistochemistry showed positive anti-neuron-specific enolase (NSE.) and anti-synaptophysin antibodies, while serum PSA was normal (1.2 ng/ml). The patient was treated by cisplatin-etoposide combination chemotherapy, but died 20 days after the first course.

  9. Small data, data infrastructures and big data (Working Paper 1)


    Kitchin, Rob; Lauriault, Tracey P.


    The production of academic knowledge has progressed for the past few centuries using small data studies characterized by sampled data generated to answer specific questions. It is a strategy that has been remarkably successful, enabling the sciences, social sciences and humanities to advance in leaps and bounds. This approach is presently being challenged by the development of big data. Small data studies will, however, continue to be important in the future because of their utility in answer...

  10. Small data in the era of big data


    Kitchin, Rob; Lauriault, Tracey P.


    Academic knowledge building has progressed for the past few centuries using small data studies characterized by sampled data generated to answer specific questions. It is a strategy that has been remarkably successful, enabling the sciences, social sciences and humanities to advance in leaps and bounds. This approach is presently being challenged by the development of big data. Small data studies will however, we argue, continue to be popular and valuable in the fut...

  11. Allergen Specific Immunotherapy

    Directory of Open Access Journals (Sweden)

    Şükrü Çekiç


    Full Text Available Allergen specific immunotherapy (SIT is the only treatment that can provide a cure for allergic disorders. This treatment is based on development of immune tolerance by exposure to allergen in repetitive and increasing doses. It is tertiary to avoidance of allergen and pharmacotherapy. Allergens used for immunotherapy, must be confirmed by skin prick test or specific IgE and must be applied in supervision of allergy specialists. Studies show that immunotherapy, improve asthma symptoms, decreases drug consumption, prevent development of asthma in rhinitis patients and reduce new sensitizations. Common side effects diminished with the usage of standardized allergen solutions. It is contraindicated in severe asthma. Though it is recommended to avoid immunotherapy in patients using beta blockers and ACE inhibitors, immunotherapy can be considered in mandatory situations regarding possible benefits and harms. Most common ways of administration are subcutaneous and sublingual; new methods such as epicutaneous and intralymphatic injections are currently being studied.

  12. Understanding the small object argument

    CERN Document Server

    Garner, Richard


    The small object argument is a transfinite construction which, starting from a set of maps in a category, generates a weak factorisation system on that category. As useful as it is, the small object argument has some problematic aspects: it possesses no universal property; it does not converge; and it does not seem to be related to other transfinite constructions occurring in categorical algebra. In this paper, we give an ``algebraic'' refinement of the small object argument, cast in terms of Grandis and Tholen's natural weak factorisation systems, which rectifies each of these three deficiencies.

  13. Cosmic Strings with Small Tension

    CERN Document Server

    Halyo, Edi


    We describe cosmic F--term strings with exponentially small tension which are D3 branes wrapped on deformed $A_3$ singularities. We show that brane instanton effects which can be calculated after a geometric transition give rise to an exponentially small volume for the node on which the D3 branes wrap leading to a string with small tension. We generalize our description to the case of non--Abelian cosmic strings and argue that these strings are stable against monopole--anti monopole pair creation.

  14. Zoonotic risks from small ruminants. (United States)

    Ganter, M


    Zoonoses are infections that spread naturally between species (sometimes by a vector) from animals to other animal species or to humans or from humans to animals. Most of the zoonoses diagnosed in sheep and goats are transmitted by close contact of man with these animals and are, more often, occupational diseases that principally affect breeders, veterinarians and/or slaughterhouse workers. Some other diseases have an airborne transmission and affect the population in the vicinity of sheep/goat farms. Due to the fact that small ruminants are almost the only remaining animals which are migrating in industrialised countries, there is a severe risk for transmitting the diseases. Some other zoonotic diseases are foodborne diseases, which are mainly transmitted from animals to humans and to other animal species by contaminated food and water. Within the last decade central Europe was threatened by some new infections, e.g., bluetongue disease and schmallenberg disease, which although not of zoonotic interest, are caused by pathogens transmitted by vectors. Causal agents of both diseases have found highly effective indigenous vectors. In the future, climate change may possibly modify conditions for the vectors and influence their distribution and competence. By this, other vector-borne zoonotic infections may propagate into former disease free countries. Changes in human behaviour in consummation and processing of food, in animal housing and management may also influence future risks for zoonosis. Monitoring, prevention and control measures are proposed to limit further epidemics and to enable the containment of outbreaks. Measures depend mainly on the damage evoked or anticipated by the disease, the local situation, and the epidemiology of the zoonoses, the presence of the infective agent in wild and other animals, as well as the resistance of the causal microorganisms in the environment and the possibility to breed sheep and goats which are resistant to specific

  15. Safety detaching hook specification.

    CSIR Research Space (South Africa)

    Roux, JD


    Full Text Available from the mean surface' and measured in micrometres (µm). Regulations Regulations pertaining to an act or amended act as promulgated by the Government of South Africa. SAATCA Southern African Auditor and Training Certification Association. SABS... of this specification have been adhered to. Technical Assessment An audit report on a manufacturer's systems for the management of product quality, issued by an independent auditor registered with SAATCA. 6 2. REQUIREMENTS 2.1 Design Requirements a) General...

  16. Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. I....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases....

  17. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. In the comp....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases. The comparative test cases include: ventilation, shading and geometry....

  18. Allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Moote William


    Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.

  19. Exploiting Specific Interactions toward Next-Generation Polymeric Drug Transporters

    NARCIS (Netherlands)

    Wieczorek, Sebastian; Krause, Eberhard; Hackbarth, Steffen; Roeder, Beate; Hirsch, Anna K. H.; Boerner, Hans G.


    A generic method describes advanced tailoring of polymer drug carriers based on polymer-block-peptides. Combinatorial means are used to select suitable peptide segments to specifically complex small-molecule drugs. The resulting specific drug formulation agents render insoluble drugs water-soluble a

  20. Road Zone Effects in Small-Mammal Communities

    Directory of Open Access Journals (Sweden)

    John A. Bissonette


    Full Text Available Our study focused on the putative effects of roads on small-mammal communities in a high desert region of southern Utah. Specifically, we tested whether or not roads create adjacent zones characterized by lower small- mammal densities, abundance, and diversity. We sampled abundance of small mammals at increasing distances from Interstate 15 during two summers. We recorded 11 genera and 13 species. We detected no clear abundance, density, or diversity effects relative to distance from the road. Only two of 13 species were never captured near roads. The abundance of the remaining 11 small mammal species was either similar at different distances from the road or higher closer to the road. We conclude that although roads may act as barriers and possible sources of mortality, adjacent zones of vegetation often provide favorable microhabitat in the desert landscape for many small mammals.

  1. Road zone effects in small-mammal communities (United States)

    Bissonette, J.A.; Rosa, S.A.


    Our study focused on the putative effects of roads on small-mammal communities in a high desert region of southern Utah. Specifically, we tested whether or not roads create adjacent zones characterized by lower small- mammal densities, abundance, and diversity. We sampled abundance of small mammals at increasing distances from Interstate 15 during two summers. We recorded 11 genera and 13 species. We detected no clear abundance, density, or diversity effects relative to distance from the road. Only two of 13 species were never captured near roads. The abundance of the remaining 11 small mammal species was either similar at different distances from the road or higher closer to the road. We conclude that although roads may act as barriers and possible sources of mortality, adjacent zones of vegetation often provide favorable microhabitat in the desert landscape for many small mammals. ?? 2009 by the author(s).

  2. Partnerships between Small and Medium Enterprises and Universities that Add Value. (United States)

    Freeman, Sue


    Marketing students' action research projects in small businesses demonstrated that small business sustainability is enhanced by increased understanding of marketing and business students' employment potential is enhanced by exposure to small businesses. Such projects also provide material for case studies on specific marketing problems. (SK)

  3. Stages of Small Intestine Cancer (United States)

    ... intestine . The digestive system removes and processes nutrients ( vitamins , minerals , carbohydrates , fats, proteins , and water) from foods ... a microscope to see whether they contain cancer. Bypass : Surgery to allow food in the small intestine ...

  4. Severe small bowel radiation enteritis

    Energy Technology Data Exchange (ETDEWEB)

    Jaen, J.; Santos, J.A.; Carrion, J.R.; Garcia, P. (Hospital General Gregorio Maranon, Madrid (Spain))


    We have during recent years observed 8 patients with serious radiation injury to the small intestine. As the cases are quite illustrative, their symptomatology is briefly reported and the treatment and possible predisposing factors are analysed. (orig./MG).

  5. Small Airframe Manufacturer's Icing Perspective (United States)

    Hoppins, Jim


    This viewgraph presentation describes the icing effects, risk mitigation practices, and icing certifications for various Cessna small aircraft models. NASA's role in the development of simulation tools for icing certifications is also discussed.

  6. Small Probe Reentry System Project (United States)

    National Aeronautics and Space Administration — Global Aerospace Corporation (GAC), and its research partner, Cal Poly San Luis Obispo (CPSLO), will develop an integrated Small Probe Reentry System (SPRS) for low...

  7. Convenient measurement of small impulses (United States)

    Brost, G.; Deaton, T.; Duvall, B.; Boyle, W.; Tinsley, J.; Bohn, C.; Stephen, M.; Souders, J.


    This paper describes a convenient method which has been used for the measurement of small impulses (1-20 dyn s). An inductive displacement gauge was used to monitor displacement of a ballistic pendulum.

  8. Small- x resummation from HELL (United States)

    Bonvini, Marco; Marzani, Simone; Peraro, Tiziano


    Small- x logarithmic enhancements arising from high-energy gluon emissions affect both the evolution of collinearly-factorized parton densities and partonic coefficient functions. With the higher collider energy reached by the LHC, the prospect of a future high-energy collider, and the recent deep-inelastic scattering (DIS) results at small- x from HERA, providing phenomenological tools for performing small- x resummation has become of great relevance. In this paper we discuss a framework to perform small- x resummation for both parton evolution and partonic coefficient functions and we describe its implementation in a computer code named High-Energy Large Logarithms ( HELL). We present resummed and matched results for the DGLAP splitting functions and, as a proof of principle, for the massless structure functions in DIS. Furthermore, we discuss the uncertainty from subleading terms on our results.

  9. Small Sat Analysis Laboratory Project (United States)

    National Aeronautics and Space Administration — The NASA Low-Cost Small Spacecraft Program is focused on the technologies, subsystems, methodologies, and mission concepts for space missions which lower the...

  10. JPL Small Body Database Browser (United States)

    National Aeronautics and Space Administration — The JPL Small-Body Database Browser provides data for all known asteroids and many comets. Newly discovered objects and their orbits are added on a daily basis....

  11. Development project of small accelerator

    CERN Document Server

    Yamada, S


    The object of this project is demonstration of a small proton and heavy ion synchrotron and a small hard X-ray photon radiation source by using new technology and application of them to therapy, diagnosis, material science and life science. In this paper, a part of small proton and heavy ion synchrotron is discussed. Nine organizations joined in this project. There are four development themes such as optimization of laser-ion 100 TW class source target, beam storage and cooling device, small synchrotron ring and FFAG accelerator. Outline and contents of development of them are explained. This project is planning to generate a few MeV/u carbon ions in fully ionized states by impact of laser with about 100 TW output. 3 T maximum bending magnetic field using normal conduction AC magnet will be actualized for synchrotron with 200 MeV proton beam. (S.Y.)

  12. Quantum Small-world Networks

    CERN Document Server

    Wei, Zong-Wen; Han, Xiao-Pu


    Quantum networks are critical to quantum communication and distributed quantum computing. Here we propose a small-world model of large-scale quantum repeater networks, where "small-world" is a fundamental concept rooted in complex networks, which describe a broad range of real systems. The core of the model is to relate the hierarchical fashion of measurements to coarse-graining process, when quantum repeater protocols are implemented. We demonstrate that quantum repeater networks with fractal structure can be enlarged with certain length scale in geographic space, while preserving topology by performing renormalization. Actually, renormalization here serves as an organizing principle determining the distribution of long-range entangled links over quantum networks, which gives rise to fractal to small-world transition. Furthermore, by iterative implementation of renormalization on the former coarse-grained network, we eventually obtain an onion-like, hierarchical quantum small-world network, where the distanc...

  13. Matrix Theory of Small Oscillations (United States)

    Chavda, L. K.


    A complete matrix formulation of the theory of small oscillations is presented. Simple analytic solutions involving matrix functions are found which clearly exhibit the transients, the damping factors, the Breit-Wigner form for resonances, etc. (BB)

  14. Small towns resisting urban decay through residential attractiveness

    DEFF Research Database (Denmark)

    Fertner, Christian; Groth, Niels Boje; Herslund, Lise Byskov;


    composition, residential migration, social organisation and community engagement form and affect small town (1000–5000 inhabitants) development patterns in Denmark and specific place-based endowments. The study is carried out with mixed methods, comprising a quantitative analysis of development trends...... of ‘residential urbanism’, the paper discusses the extent to which a residentially driven urban development can compensate for the generally unfavourable regional development context......Small towns are often considered as losing out in the current trend towards urban development. However, research from around Europe shows a great diversity of small town development, including successful development trajectories despite geographical disadvantages. Investigations...

  15. MR imaging of small liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sekoguchi, Bon; Horiguchi, Yuji; Takagawa, Hiroko (Fujita-Gakuen Health Univ., Toyoake, Aichi (Japan)) (and others)


    With recent development of diagnostic modalities, many hepatic nodules smaller than 2 cm in diameter have been able to be detected in patients with chronic liver diseases. Magnetic resonance imaging (MRI) is one of the most efficacious modalities for detecting small nodules and differentiating carcinoma from other benign lesions. In this paper, we present specific findings on MRI to small liver cancer. Signal intensity of the tumor on T1-weighted images was high in 12 (63%) out of 19 cases, T2-weighted images showed hyperintensity of the tumor in 14 cases (74%), and isointensity in 5 cases. To compare the signal intensity on MRI with the echo level on ultrasound, hypoechoic lesions represented hyperintensity on T1-weighted images in 6 of 11 cases, and isointensity 5 cases. The latter pattern was considered to be consistent with compact type hepatocellular carcinomas, but the pathogenesis of the former pattern remained uncertain. With respect to hyperechoic nodules, MRI showed hyperintensity on T1-weighted images in 6 of 8 cases; these findings were common in fatty change of tumor cells. In conclusion, characteristic findings on MRI in small liver cancer are hyperintensity on T1-weighted images; its pathogenesis is in part fatty change in the tumor, but unknown in the remaining cases. (author).

  16. Small RNA combination therapy for lung cancer (United States)

    Xue, Wen; Dahlman, James E.; Tammela, Tuomas; Khan, Omar F.; Sood, Sabina; Dave, Apeksha; Cai, Wenxin; Chirino, Leilani M.; Yang, Gillian R.; Bronson, Roderick; Crowley, Denise G.; Sahay, Gaurav; Schroeder, Avi; Langer, Robert; Anderson, Daniel G.; Jacks, Tyler


    MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. PMID:25114235

  17. DASHR: database of small human noncoding RNAs. (United States)

    Leung, Yuk Yee; Kuksa, Pavel P; Amlie-Wolf, Alexandre; Valladares, Otto; Ungar, Lyle H; Kannan, Sampath; Gregory, Brian D; Wang, Li-San


    Small non-coding RNAs (sncRNAs) are highly abundant RNAs, typically database provides searchable, unified annotation, and expression information for full sncRNA transcripts and mature RNA products derived from these larger RNAs. Here, we present the Database of small human noncoding RNAs (DASHR). DASHR contains the most comprehensive information to date on human sncRNA genes and mature sncRNA products. DASHR provides a simple user interface for researchers to view sequence and secondary structure, compare expression levels, and evidence of specific processing across all sncRNA genes and mature sncRNA products in various human tissues. DASHR annotation and expression data covers all major classes of sncRNAs including microRNAs (miRNAs), Piwi-interacting (piRNAs), small nuclear, nucleolar, cytoplasmic (sn-, sno-, scRNAs, respectively), transfer (tRNAs), and ribosomal RNAs (rRNAs). Currently, DASHR (v1.0) integrates 187 smRNA high-throughput sequencing (smRNA-seq) datasets with over 2.5 billion reads and annotation data from multiple public sources. DASHR contains annotations for ∼ 48,000 human sncRNA genes and mature sncRNA products, 82% of which are expressed in one or more of the curated tissues. DASHR is available at

  18. Retroperitoneal liposarcoma associated with small plaque parapsoriasis

    Directory of Open Access Journals (Sweden)

    Polichetti Paolo


    Full Text Available Abstract Background Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. Production of Granulocyte-Colony Stimulating Factor, alpha-fetoprotein, paraneoplastic pemphigus and leucocytosis, Acrokeratosis paraneoplastica (Bazex's syndrome are reported. The present report describes a case of retroperitoneal liposarcoma associated with small plaque parapsoriasis. Our search in the English literature of such a kind of association did not reveal any case reported. Case presentation A 74 year male patient was admitted to our hospital because of the presence of an abdominal mass in right iliac fossa. He also complained of a two-year history of psoriasiform eruptions. The CT scan showed a retroperitoneal pelvic mass. Therefore surgical resection of the tumor was performed. After surgery, the skin eruptions disappeared completely in seven days and so a diagnosis of parapsoriasis syndrome was done. Conclusion Parallel disappearing of skin eruptions after surgery, typical clinical picture and not specific histology of the cutaneous lesions suggest the diagnosis of small plaque parapsoriasis. Therefore we propose to add Small Plaque Parapsoriasis to the list of paraneoplastic syndromes associated to liposarcoma.

  19. Small and Scenic Fenghuang City

    Institute of Scientific and Technical Information of China (English)


    FENGHUANG(Chinese for phoenix), a small city under the jurisdiction of the Tujia Autonomous Prefecture of Hunan Province, borders northern Guizhou Province and eastern Chongqing Municipality. Surrounded by mountains and girdled by the Tuojiang River, this small, quiet city is famous for its beautiful landscape, and as birthplace of several celebrated Chinese personages.Fenghuang’s history dates back 1,316 years. It was originally named Weiyang, and its location was in today’s Huangsiqiao

  20. Small Bowel Review - Part I


    Thomson, ABR; Wild, G.


    Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleosides, nucleotides and polyamines; salt and water absorption, and diarrhea, including antidiarrheal therapy and oral rehydration treatment; lipids (digestion and absorption...

  1. Small Satellite Reaction Wheel Optimization


    Michaelis, Ted


    The very "smallness" of small satellites mandates mass minimization. This paper addresses minimization of overall reaction wheel mass, including the incremental mass of the power subsystem needed to support the reaction wheel. The results are applicable to a wide range of wheel sizes and are suitable for optimization at the configuration level. For an average momentum and torque operating point, the minimization process yields wheel radius and angular velocity, as well as, the masses associat...

  2. Identification of the Paneth cells in chicken small intestine. (United States)

    Wang, L; Li, J; Li, J; Li, R X; Lv, C F; Li, S; Mi, Y L; Zhang, C Q


    The Paneth cells are highly specialized cells in the epithelium of the small intestine of many vertebrate species. These cells reside at the base of crypts of the Lieberkühn and contain abundant secretory granules. Previous studies suggesting the existence of Paneth cells in the chicken (Gallus gallus) remained controversial. Here we seek to identify the Paneth cells in the chicken small intestine through morphological examination and specific gene expression. Histological staining and transmission electron microscope confirmed the presence of granulated secretory cells at the base of the crypts in the chicken small intestine. Western blotting experiment also manifested the expression of lysozyme protein, which is specifically secreted by the Paneth cells in the small intestine. Moreover, lysozyme c and lysozyme g mRNAs were expressed in the small intestine of chickens at different ages. Lysozyme c mRNA, in particular, was located at the base of the small intestinal crypts as displayed by in situ hybridization. Collectively, we provide evidences that the Paneth cells indeed exist in the small intestine of the chicken.

  3. World Small Hydropower Development Report

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Heng; Esser, Lara (ICSGP (China)); Masera, Diego (UNIDO, Vienna (Austria))


    Currently, small hydropower plants with a capacity of 10 MW, exist in 148 countries or territories worldwide. Four other countries have been identified with resource potential. This report aims to identify the development status and resource potential of small hydro in various countries, territories and regions throughout the world. Working with experts at the ground level to compile and share existing information, experiences and challenges, one comprehensive report was created. Decision-makers, stakeholders and potential investors clearly need this comprehensive information to more effectively promote small hydropower as a renewable and rural energy source for sustainable development and to overcome the existing development barriers. The findings of this report show that small hydropower potential globally is approximated at almost 173 GW. The figure is arrived by totaling data from a wide range of sources with potential compromise of data integrity to varying degrees. For example, research data on economically feasible potential were more readily available in developed countries than those in the least developed or developing countries. More than half of the world's known hydropower potential is located in Asia, around one third can be found in Europe and the Americas. It is possible in the future that more small hydropower potential might be identified both on the African and American continents. The installed small hydropower capacity (up to 10 MW) is estimated to be 75 GW in 2011/2012. The report provides detailed data for each country/region, including recommendations on the national, regional and international level.

  4. Small group discussion: Students perspectives. (United States)

    Annamalai, Nachal; Manivel, Rajajeyakumar; Palanisamy, Rajendran


    Various alternative methods are being used in many medical colleges to reinforce didactic lectures in physiology. Small group teaching can take on a variety of different tasks such as problem-solving, role play, discussions, brainstorming, and debate. Research has demonstrated that group discussion promotes greater synthesis and retention of materials. The aims of this study were to adopt a problem-solving approach by relating basic sciences with the clinical scenario through self-learning. To develop soft skills, to understand principles of group dynamics, and adopt a new teaching learning methodology. Experimental study design was conducted in Phase I 1(st) year medical students of 2014-2015 batch (n = 120). On the day of the session, the students were grouped into small groups (15 each). The session started with the facilitator starting off the discussion. Feedback forms from five students in each group was taken (n = 40). A five point Likert scale was used ranging from strongly agree to strongly disagree. Data were analyzed using IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp. Our results show that 70% of the students opined that small group discussion were interactive, friendly, innovative, built interaction between teacher and student. Small group discussion increased their thought process and helped them in better communication. The small group discussion was interactive, friendly, and bridged the gap between the teacher and student. The student's communication skills are also improved. In conclusion, small group discussion is more effective than the traditional teaching methods.

  5. Accelerator mass spectrometry of small biological samples. (United States)

    Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran


    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of microg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A (12)C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

  6. Thermodynamic properties of ultra-small metallic particles

    Institute of Scientific and Technical Information of China (English)

    Cheng Nan-Pu; Zeng Su-Min; Chen Zhi-Qian


    The thermodynamic properties of ultra-small metallic particles within an ensemble are affected by the level distribution and the level correlation between the discrete electronic energy levels. The specific heat and spin susceptibility of ultra-small metallic particles in the canonical ensemble with an odd or even number of electrons are numerically calculated by considering the effects of the level statistics, and their behaviour at low and high temperatures is also discussed. As an example, the specific heat and spin susceptibility of nano-Al particles are calculated numerically in this paper.

  7. Small molecule screening identifies targetable zebrafish pigmentation pathways

    DEFF Research Database (Denmark)

    Colanesi, Sarah; Taylor, Kerrie L; Temperley, Nicholas D


    Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investig......Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish...

  8. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract......Concurrent objects are named concurrent processes that interact by invoking each other's operations. We describe how such concurrent objects can be specified, how objects can be composed, and how it can be shown that one object refines another.First a model is defined, based on a transition...

  9. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer (United States)


    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  10. Disease specific protein corona (United States)

    Rahman, M.; Mahmoudi, M.


    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  11. Small Bowel and Liver/Small Bowel Transplantation in Children (United States)

    Reyes, Jorge; Tzakis, Andreas G.; Todo, Satoru; Nour, Bakr; Starzl, Thomas E.


    A clinical trial of intestinal transplantation was initiated at the University of Pittsburgh in May 1990. Eleven children received either a combined liver/small bowel graft (n = 8) or an isolated small bowel graft (n = 3). Induction as well as maintenance immunosuppression was with FK-506 and steroids. Four patients were male, and seven were female; the age range was 6 months to 10.2 years. There were 3 deaths (all in recipients of the combined liver/small bowel graft), which were attributed to graft-versus-host disease (n = 1), posttransplant lymphoproliferative disease (n = 1), and biliary leak (n = 1). Transplantation of the intestine has evolved into a feasible operation, with an overall patient and graft survival rate of 73%. These survivors are free of total parenteral nutrition, and the majority are home. These encouraging results justify further clinical trials. PMID:8062049


    Directory of Open Access Journals (Sweden)



    Full Text Available Development of small injection moulding machine for forming small plastic articles in small-scale industries was studied. This work which entailed design, construction and test small injection moulding machine that was capable of forming small plastic articles by injecting molten resins into a closed, cooled mould, where it solidifies to give the desired products was developed. The machine was designed and constructed to work as a prototype for producing very small plastic components. Design concept, operation, and assembly of components parts were made. Also, working drawings and materials selection were made based on calculations of the diameter of injection plunger, number of teeth required for the plunger rack and spur gear, the angular velocity, number of revolution, torque and power obtained from the electric motor selected and the leverage on the handle of the machine. The machine parts/components were then assembled in line with the designed made, thereafter the constructed machine was tested using high density polyethylene and master batch. The results obtained from the test were satisfactory.

  13. Small bowel faeces sign in patients without small bowel obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, S.L. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States)]. E-mail:; Rozenblit, A. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States); Ricci, Z. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States); Roberts, J. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States); Milikow, D. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States); Chernyak, V. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States); Wolf, E. [Department of Radiology, Montefiore Medical Center, Bronx, NY (United States)


    Aim: To evaluate frequency and clinical relevance of the 'small bowel faeces' sign (SBFS) on computed tomography (CT) in patients with and without small bowel obstruction (SBO) presenting with acute abdominal or acute abdominal and flank pain. Methods: Abdominal CTs of consecutive patients presenting to the emergency department with abdominal or flank pain over a 6 month period were retrospectively reviewed by six radiologists, independently, for the presence of the SBFS. Examinations with positive SBFS were further evaluated in consensus by three radiologists, blinded to the final diagnosis. The small bowel was graded as non-dilated (<2.5 cm) and mildly (2.5-2.9 cm), moderately (3-4 cm) or severely (>4 cm) dilated. The location of SBFS and presence of distal small bowel collapse indicative of SBO was recorded. Imaging findings were subsequently correlated with the final diagnosis via chart review and compared between patients with and without SBO. Results: Of 1642 CT examinations, a positive SBFS was found in 100 (6%) studies. Of 100 patients with a positive SBFS, 32 (32%) had documented SBO. The remaining 68 patients had other non-obstructive diagnoses. SBFS was located in proximal, central, distal and multisegmental bowel loops in one (3.1%), eight (25.0%), 21 (65.6%) and two (6.3%) patients with SBO, and in zero (0%), 10 (14.7%), 53 (77.9%) and five (7.4%) of patients without SBO (p < 0.273). The small bowel was non-dilated and mildly, moderately or severely dilated in one (3%), five (16%), 20 (62%) and six (19%) patients with SBO, and in 61(90%), seven (10%), zero (0%) and zero (0%) patients without SBO. Normal or mildly dilated small bowel was seen in all (100%) patients without SBO, but only in six (19%) of 32 patients with SBO (p < 0.0001). Moderate or severe small bowel dilatation was seen in 26 (81%) patients with SBO (p < 0.0001), but it was absent in patients without SBO. Distal small bowel collapse was found in 27 (84.4%) of 32 patients with

  14. 肺特异性X蛋白基因在PNO期非小细胞肺癌淋巴结微转移中的表达及临床意义%Expression of lung-specific X protein in non small cell lung cancer lymph node metastasis and the clinical significance

    Institute of Scientific and Technical Information of China (English)

    邬冬强; 杜开齐; 张志豪; 朱有才; 肖怀清; 王细勇; 陈华飞


    Objective To investigate the detection of lymph node micrometastasis in stage Ⅰ nonsmall cell lung cancers (NSCLC) using lung-specific X protein (LUNX) mRNA as a marker based on reverse transcription-polymerase chain reaction (RT-PCR) and its relationship with the patho-clinical features and prognosis.Methods 52 patients underwent curative lobectomy,excluding pneumonectomy and Palliative resection.Curative lobeetomy included systemic lymph node reseetion,Which meant at least 6 mediastinal lymph node from 3 stations were reseeted.The expression of LUNX mRNA in each station of lymph node were examined by means of RT-PCR.LUNX mRNA was then used as a marker of lymph node micrometastasis.Analyses of relationship between lymph node micrometastasis and the pathoclinical features,overall survival and disease free survival were then carried out.Results The expression of LUNX mRNA:none was positive for all ten lymph nodes from benign diseases.All 52 lung cancer tissues showed positive expression,14.98% of lymph nodes and 12.24% of mediastinal lymph nodes showed positive expression,so that the LUNX stage was upgraded.Survival affecting factors included:LUNX stage (P < 0.01),mediastinal lymph nodes micrometastasis (P < 0.01),number of lymph nodes and mediastinal lymph nodes resected (P < 0.05),pathological differentiation (P < 0.05).Those with mediastinal lymph nodes micrometastasis had a 21.8 folds higher risk of death than those without (P < 0.01).Conclusion The expression of LUNX mRNA in lymph nodes is related to overall survival and disease free survival,and is a reflection of lymph nodes micrometastasis.The subgroup of stage propidium iodide (PI) patients with high risks can be thus found.This technique is helpful in restaging patients more accurately.Survival can be improved if interference is applied in early stage.%目的 观察肺特异性X蛋白(LUNX)在PN0期非小细胞肺癌(NSCLC)原发病灶和转移淋巴结中的表达,探讨LUNX在PN0期NSCLC

  15. Tumours in the Small Bowel

    Directory of Open Access Journals (Sweden)

    N. Kurniawan


    Full Text Available Small bowel tumours are rare and originate from a wide variety of benign and malignant entities. Adenocarcinomas are the most frequent primary malignant small bowel tumours. Submucosal tumours like gastrointestinal stromal tumours (GIST or neuroendocrine tumours (NET may show a central umbilication, pathologic vessels, bridging folds or an ulceration of the overlying mucosa. These signs help to differentiate them from harmless bulges caused by impression from outside, e.g. from other intestinal loops. Sarcomas of the small bowel are rare neoplasias with mesenchymal origin, sometimes presenting as protruding masses. Benign tumours like lipoma, fibrolipoma, fibroma, myoma, and heterotopias typically present as submucosal masses. They cannot be differentiated endoscopically from those with malignant potential as GIST or NET. Neuroendocrine carcinomas may present with diffuse infiltration, which may resemble other malignant tumours. The endoscopic appearance of small bowel lymphomas has a great variation from mass lesions to diffuse infiltrative changes. Melanoma metastases are the most frequent metastases to the small bowel. They may be hard to distinguish from other tumours when originating from an amelanotic melanoma.

  16. Small-ductprimarysclerosingcholangitis withhepatocellularcarcinomarequiringliver transplantation

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Veena Shah


    BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease, which usually affects young adults and is diagnosed by cholangiography. On a few occasions, the disease either starts in or exclusively involves the small intrahepatic bile ducts, referred to as small-duct PSC. METHODS: A 31-year-old man presented with severe hematemesis secondary to liver cirrhosis. Over a course of 8 years, his liver decompensated and required an orthotopic liver transplantation. In this report we discuss his disease presentation, course of management, and the post-transplantation course of manage-ment, and review the morphologic diagnosis, and differential diagnosis of the disease with large-duct type and other diseases that involve small intrahepatic bile ducts. RESULTS:The patient's explanted liver showed changes of PSC affecting only the small- and medium-sized bile ducts in addition to three incidental nodules of hepatocellular carcinoma. CONCLUSIONS: Small-duct PSC has a substantially better prognosis than the large-duct type, with less chance of developing cirrhosis and an equal risk for developing hepato-cellular carcinoma, but no increased risk for developing cholangiocarcinoma. Treatment seems to help relieve the symptoms but not necessarily improve survival. Liver transplantation remains the ultimate cure.

  17. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik


    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  18. Industry Research and Recommendations for Small Buildings and Small Portfolios

    Energy Technology Data Exchange (ETDEWEB)

    Langner, Rois [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hendron, Bob [National Renewable Energy Lab. (NREL), Golden, CO (United States); Pless, Shanti [National Renewable Energy Lab. (NREL), Golden, CO (United States); Huppert, Mark [National Trust for Historic Preservation, Washington, DC (United States); Cochrane, Ric [National Trust for Historic Preservation, Washington, DC (United States)


    Small buildings have been left behind in the energy efficiency marketplace because financial and technical resources have flowed to larger commercial buildings. DOE's Building Technologies Office works with the commercial building industry to accelerate the uptake of energy efficiency technologies and techniques in existing and new commercial buildings (DOE 2013). BTO recognizes the SBSP sector'spotential for significant energy savings and the need for investments in resources that are tailored to this sector's unique needs. The industry research and recommendations described in this report identify potential approaches and strategic priorities that BTO could explore over the next 3-5 years that will support the implementation of high-potential energy efficiency opportunities for thisimportant sector. DOE is uniquely positioned to provide national leadership, objective information, and innovative tools, technologies, and services to support cost-effective energy savings in the fragmented and complex SBSP sector. Properly deployed, the DOE effort could enhance and complement current energy efficiency approaches. Small portfolios are loosely and qualitatively defined asportfolios of buildings that include only a small number of small buildings. This distinction is important because the report targets portfolio owners and managers who generally do not have staff and other resources to track energy use and pursue energy efficiency solutions.

  19. Marketing the Uniqueness of Small Towns. Small Town Strategy. (United States)

    Hogg, David H.; Dunn, Douglas

    A small town can strengthen its local economy as a result of business people and concerned citizens collectively identifying that community's uniqueness and then capitalizing on it via advertising, personal selling, sales promotion, or publicity. This publication relates the science of marketing to communities. Seven simple techniques are provided…

  20. Purchasing cooperatives for small employers. (United States)

    Mallozzi, J


    Despite a booming economy, the number of uninsured Americans is rising. It hit nearly 42 million in 1996. Many of the uninsured work at businesses with fewer than 50 employees. Because small firms have traditionally found it difficult to provide health benefits, purchasing cooperatives have grown in scope and size across the country in recent years. By bringing small businesses together to buy insurance as a group, these organizations can help employers provide greater choice to their workers at a lower cost. However, to operate well in the insurance market, purchasing cooperatives must be well-designed and provided with adequate legal protections.

  1. Small Bowel Review - Part I

    Directory of Open Access Journals (Sweden)

    ABR Thomson


    Full Text Available Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleosides, nucleotides and polyamines; salt and water absorption, and diarrhea, including antidiarrheal therapy and oral rehydration treatment; lipids (digestion and absorption, fatty acid binding proteins, intracellular metabolism, lipoproteins and bile acids; and metals (eg, iron and vitamins.

  2. Appropriate technology for small turbines

    Energy Technology Data Exchange (ETDEWEB)

    Strohmer, F.; Walch, E.


    The investment costs of small-scale hydro plants are relatively high; of these the electro-mechanical equipment is generally a high proportion. One way of reducing these costs is to use information and experience gained in the manufacture of equipment for large plants, avoiding expensive testing and assessment. To exploit this experience, a standard program has been developed which can be applied quickly and easily for the design of small turbines. In this way the best choice of turbines and configurations can be determined rapidly for any site.

  3. Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care Hospitals and the Long-Term Care Hospital Prospective Payment System Policy Changes and Fiscal Year 2016 Rates; Revisions of Quality Reporting Requirements for Specific Providers, Including Changes Related to the Electronic Health Record Incentive Program; Extensions of the Medicare-Dependent, Small Rural Hospital Program and the Low-Volume Payment Adjustment for Hospitals. Final rule; interim final rule with comment period. (United States)


    We are revising the Medicare hospital inpatient prospective payment systems (IPPS) for operating and capital related costs of acute care hospitals to implement changes arising from our continuing experience with these systems for FY 2016. Some of these changes implement certain statutory provisions contained in the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010 (collectively known as the Affordable Care Act), the Pathway for Sustainable Growth Reform(SGR) Act of 2013, the Protecting Access to Medicare Act of 2014, the Improving Medicare Post-Acute Care Transformation Act of 2014, the Medicare Access and CHIP Reauthorization Act of 2015, and other legislation. We also are addressing the update of the rate-of-increase limits for certain hospitals excluded from the IPPS that are paid on a reasonable cost basis subject to these limits for FY 2016.As an interim final rule with comment period, we are implementing the statutory extensions of the Medicare dependent,small rural hospital (MDH)Program and changes to the payment adjustment for low-volume hospitals under the IPPS.We also are updating the payment policies and the annual payment rates for the Medicare prospective payment system (PPS) for inpatient hospital services provided by long-term care hospitals (LTCHs) for FY 2016 and implementing certain statutory changes to the LTCH PPS under the Affordable Care Act and the Pathway for Sustainable Growth Rate (SGR) Reform Act of 2013 and the Protecting Access to Medicare Act of 2014.In addition, we are establishing new requirements or revising existing requirements for quality reporting by specific providers (acute care hospitals,PPS-exempt cancer hospitals, and LTCHs) that are participating in Medicare, including related provisions for eligible hospitals and critical access hospitals participating in the Medicare Electronic Health Record (EHR)Incentive Program. We also are updating policies relating to the

  4. Detection of epidermal growth factor receptor gene mutation in non-small cell lung cancer by allelespecific oligonucleotide-PCR and bi-loop probe specific primer quantitative PCR%等位基因特异性寡核苷酸和双环探针特异引物荧光聚合酶链反应检测非小细胞肺癌表皮生长因子受体基因突变

    Institute of Scientific and Technical Information of China (English)

    邓磊; 李甘地; 卢铀; 唐源; 林静; 陆小军; 薛建新; 王立帅; 周麟; 邹艳; 应斌武


    Objective To compare the detection sensitivity of epidermal growth factor receptor (EGFR) mutations between allele specific oligonucleotide PCR(ASO-PCR) and bi-loop probe and specific primer quantitative PCR (BPSP-qPCR).Methods A total of 96 non-small cell lung cancer specimens were selected from West China Hospital from September 2009 to December 2010.ASO-PCR was developed to detect the presence of classical EGFR mutations.A total 39 available specimens were also tested by BPSP- qPCR.Results EGFR mutation detection rate was 30.2% (26/96) by ASO-PCR.The mutation rate was higher in female than in male patients[45.5% (20/44) vs.17.3% (9/52),P =0.003],non-smokers than smokers[ 44.1% (26/59) vs.8.1% (3/37),P < 0.001 ] and adenocarcinomas than other subtypes of lung cancer [ 37.0% ( 27/73 ) vs.8.7% (2/23),P =0.01 ].Among mutation negative cases by ASO-PCR,BPSP-qPCR increased the rate of detection of 19-del and L858R mutation by 10.3% (4/39) inadenocarcinomas and non-smoking subset.Overall,the mutation detection rate of BPSP-qPCR was higher than that of ASO-PCR [66.7% (26/39) vs.41.0% (16/39),P=0.02].Conclusion BPSP-qPCR has a better detection sensitivity than that of ASO-PCR.%目的 分析比较等位基因特异性寡核苷酸聚合酶链反应( ASO -PCR)和双环探针特异引物荧光PCR (BPSP-qPCR)的表皮生长因子受体(EGFR)基因突变检测敏感性.方法 收集2009年9月至2010年12月在四川大学华西医院病理科留存非小细胞肺癌标本96例,行ASO-PCR检测EGFR突变,其中39例再行BPSP-qPCR检测.结果 ASO-PCR测得突变率为30.2% (29/96).其中女性高于男性[45.5% (20/44)比17.3% (9/52),P=0.003],不吸烟者高于吸烟者[44.1% (26/59)比8.1% (3/37),P<0.001],腺癌高于非腺癌[37.0% (27/73)比8.7% (2/23),P=0.01].ASO-PCR检测阴性标本中,具有腺癌和不吸烟特征,BPSP-qPCR检测19-del和L.858R阳性的检出率可提高10.3% (4/39),BPSP-qPCR检

  5. ADANS database specification

    Energy Technology Data Exchange (ETDEWEB)



    The purpose of the Air Mobility Command (AMC) Deployment Analysis System (ADANS) Database Specification (DS) is to describe the database organization and storage allocation and to provide the detailed data model of the physical design and information necessary for the construction of the parts of the database (e.g., tables, indexes, rules, defaults). The DS includes entity relationship diagrams, table and field definitions, reports on other database objects, and a description of the ADANS data dictionary. ADANS is the automated system used by Headquarters AMC and the Tanker Airlift Control Center (TACC) for airlift planning and scheduling of peacetime and contingency operations as well as for deliberate planning. ADANS also supports planning and scheduling of Air Refueling Events by the TACC and the unit-level tanker schedulers. ADANS receives input in the form of movement requirements and air refueling requests. It provides a suite of tools for planners to manipulate these requirements/requests against mobility assets and to develop, analyze, and distribute schedules. Analysis tools are provided for assessing the products of the scheduling subsystems, and editing capabilities support the refinement of schedules. A reporting capability provides formatted screen, print, and/or file outputs of various standard reports. An interface subsystem handles message traffic to and from external systems. The database is an integral part of the functionality summarized above.

  6. Tissue specific electrochemical fingerprinting.

    Directory of Open Access Journals (Sweden)

    Pavlina Sobrova

    Full Text Available BACKGROUND: Proteomics and metalloproteomics are rapidly developing interdisciplinary fields providing enormous amounts of data to be classified, evaluated and interpreted. Approaches offered by bioinformatics and also by biostatistical data analysis and treatment are therefore of extreme interest. Numerous methods are now available as commercial or open source tools for data processing and modelling ready to support the analysis of various datasets. The analysis of scientific data remains a big challenge, because each new task sets its specific requirements and constraints that call for the design of a targeted data pre-processing approach. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a mathematical approach for evaluating and classifying datasets obtained by electrochemical analysis of metallothionein in rat 9 tissues (brain, heart, kidney, eye, spleen, gonad, blood, liver and femoral muscle. Tissue extracts were heated and then analysed using the differential pulse voltammetry Brdicka reaction. The voltammograms were subsequently processed. Classification models were designed making separate use of two groups of attributes, namely attributes describing local extremes, and derived attributes resulting from the level=5 wavelet transform. CONCLUSIONS/SIGNIFICANCE: On the basis of our results, we were able to construct a decision tree that makes it possible to distinguish among electrochemical analysis data resulting from measurements of all the considered tissues. In other words, we found a way to classify an unknown rat tissue based on electrochemical analysis of the metallothionein in this tissue.

  7. Site-specific

    Directory of Open Access Journals (Sweden)

    Adel M.E. Mohamed


    Full Text Available In order to quantify the near-surface seismic properties (P- and S-wave velocities, and the dynamic elastic properties with respect to the depth at a specific area (6th of October club, we conducted a non-invasive and low cost active seismic survey. The primary wave velocity is determined by conducting a P-wave shallow seismic refraction survey. The dispersive characteristics of Rayleigh type surface waves were utilized for imaging the shallow subsurface layers by estimating the 1D (depth and 2D (depth and surface location shear wave velocities. The reliability of the Multi-channel Analysis of Surface Waves (MASW depends on the accurate determination of phase velocities for horizontally traveling fundamental mode Rayleigh waves. Consequently, the elastic properties are evaluated empirically. The Vs30 (average shear wave velocity down to 30 m depth, which is obtained from the MASW technique, plays a critical role in evaluating the site response of the upper 30 m depth. The distribution of the obtained values of Vs30 through the studied area demonstrates site classes of C and D, according to the NEHRP (National Earthquake Hazard Reduction Program and IBC (International Building Code standards.

  8. Department of the Navy Small Business Programs (United States)


    small business concerns and to women -owned small business concerns eligible under the Women -Owned Small Business Program. The dollar...2014 For All US-Based Women Owned Small Business Awards Over $ 200M Over $ 100M Over...Department of the Navy Small Business Programs Gold Coast August 13, 2014 Report Documentation Page Form ApprovedOMB No. 0704-0188

  9. Attenuation of microwaves by poly-disperse small spheroid particles (United States)

    Zhang, Peichang; Wang, Zhenhui


    Expressions for calculating the attenuation cross sections of poly-disperse, small spheroids, whose rotatory axes are in specific status, have been derived from a universal formula for calculating the attenuation cross section of a particle of arbitrary shape. Attenuation cross sections of liquid, ice, and spongy spheroidal droplets in different size and eccentricity at different wave lengths have been computed and analyzed.

  10. The biogenesis and function of small RNAs in C. elegans

    NARCIS (Netherlands)

    Tops, B.B.J.


    RNAi is the process by which double-stranded RNA (dsRNA) induces sequence-specific mRNA degradation. DsRNA is diced into small interfering RNAs (siRNAs) of ~21-23 nt by a complex containing the RNaseIII enzyme DICER. The mature siRNAs are subsequently bound by Argonaute proteins and incorporated int

  11. The biogenesis and function of small RNAs in C. elegans

    NARCIS (Netherlands)

    Tops, B.B.J.


    RNAi is the process by which double-stranded RNA (dsRNA) induces sequence-specific mRNA degradation. DsRNA is diced into small interfering RNAs (siRNAs) of ~21-23 nt by a complex containing the RNaseIII enzyme DICER. The mature siRNAs are subsequently bound by Argonaute proteins and incorporated int

  12. Topology Optimization of Metamaterial-Based Electrically Small Antennas

    DEFF Research Database (Denmark)

    Erentok, Aycan; Sigmund, Ole


    A topology optimized metamaterial-based electrically small antenna configuration that is independent of a specific spherical and/or cylindrical metamaterial shell design is demonstrated. Topology optimization is shown to provide the optimal value and placement of a given ideal metamaterial in space...

  13. Small-molecule control of protein function through Staudinger reduction (United States)

    Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander


    Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

  14. Hispanic Women Small Business Owners. (United States)

    Sarason, Yolanda; Koberg, Christine


    A survey of 22 Hispanic women who owned small businesses in a western state found that most were located in metropolitan areas, were new to business ownership, had started the business themselves, engaged in "miscellaneous services," and generated lower than average revenues. Respondents were similar to nonminority owners in educational…

  15. Small store presence in Japan

    NARCIS (Netherlands)

    M.A. Carree (Martin); J.C.A. Potjes; A.R. Thurik (Roy)


    textabstractThe determinants of the development of small store presence in Japan are investigated using a fixed effects multinomial logit market share model. Large stores tend to have higher market shares in shop-types with increasing shares in consumer expenditures, increasing inventory turnover,

  16. Economics: An Emerging Small World?

    NARCIS (Netherlands)

    S. Goyal (Sanjeev); M.J. van der Leij (Marco); J.L. Moraga-Gonzalez (José Luis)


    textabstractThis paper examines the small world hypothesis. The first part of the paper presents empirical evidence on the evolution of a particular world: the world of journal publishing economists during the period 1970-2000. We find that in the 1970's the world of economics was a collection of is

  17. Disorders of the Small Intestine (United States)

    ... peristaltic). They occur mostly in the upper small intestine and fade out before moving too far down-stream. They occur in most people at infrequent intervals, but in patients with irritable bowel syndrome (IBS) they may be associated with abdominal pain. ...

  18. Calculator. Owning a Small Business. (United States)

    Parma City School District, OH.

    Seven activities are presented in this student workbook designed for an exploration of small business ownership and the use of the calculator in this career. Included are simulated situations in which students must use a calculator to compute property taxes; estimate payroll taxes and franchise taxes; compute pricing, approximate salaries,…

  19. Small Secondary Schools Administrative Manual. (United States)

    Alaska State Dept. of Education, Juneau. Office of Public Information and Publications.

    A guideline for providing quality secondary education in situations where only a relatively small number of students are involved, this manual describes the organizational options for high school programs. The options discussed are regional high schools, area secondary schools, and local high schools. Local high schools can be further classified…

  20. Small Molecule PET-Radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip H.; Dierckx, Rudi A. J. O.


    This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in C-11 and F-18-radiochemistry are summarized. In addition an update o

  1. New Russian Combat Small Boats

    Directory of Open Access Journals (Sweden)

    Aleksandr F. Mitrofanov


    Full Text Available The article presents an overview of small combat boats. The author provides a description and gives an analysis of the characteristics of the boat "Raptor", boat "BK-16", boat "Strizh-4-1 DSh", and assault boat "BK-10".

  2. Small Mammals, Reptiles, and Amphibians (United States)

    Bryce Rickel


    This chapter focuses on small mammals, reptiles, and amphibians that inhabit the grasslands within the Southwestern Region of the USDA Forest Service. The chapter is not intended to be an all inclusive list of species, but rather to address the species that play important roles in grassland ecosystems and that often are associated with the management of grasslands....

  3. Exact completions and small sheaves

    CERN Document Server

    Shulman, Michael


    We prove a general theorem which includes most notions of "exact completion". The theorem is that "k-ary exact categories" are a reflective sub-2-category of "k-ary sites", for any regular cardinal k. A k-ary exact category is an exact category with disjoint and universal k-small coproducts, and a k-ary site is a site whose covering sieves are generated by k-small families and which satisfies a weak size condition. For different values of k, this includes the exact completions of a regular category or a category with (weak) finite limits; the pretopos completion of a coherent category; and the category of sheaves on a small site. For a large site with k the size of the universe, it gives a well-behaved "category of small sheaves". Along the way, we define a slightly generalized notion of "morphism of sites", and show that k-ary sites are equivalent to a type of "enhanced allegory".

  4. Small firm transformation through IS

    NARCIS (Netherlands)

    Levy, Margi; Powell, Philip


    Globally, Small and Medium-sized Enterprises (SMEs) are encouraged, particularly by governments, to embrace c-business. Fully adopting e-business involves substantial change in firms, both internally and externally. However, there is little understanding of the mechanisms by which such business

  5. Small bowel transplantation: An overview

    NARCIS (Netherlands)

    R.W.F. de Bruin (Ron); E. Heineman (Erik); R.L. Marquet (Richard)


    textabstractSmall bowel transplantation (SBT) would, in theory, be the treatment of choice for patients suffering from the short bowel syndrome. Although SBT has been done with a considerable degree of success in some centers [36,145], it is by no means an established or widely applicable therapy fo

  6. Small firm transformation through IS

    NARCIS (Netherlands)

    Levy, Margi; Powell, Philip


    Globally, Small and Medium-sized Enterprises (SMEs) are encouraged, particularly by governments, to embrace c-business. Fully adopting e-business involves substantial change in firms, both internally and externally. However, there is little understanding of the mechanisms by which such business tran

  7. Biological productivity in small impoundments (United States)

    Most ponds and small impoundments are built or used with a principal use in mind. That use may be recreational fishing, commercial aquaculture, waterfowl hunting, potable water storage, irrigation water supply, livestock watering, stormwater retention, landscaping, swimming, or others. In practice, ...

  8. Small artery remodelling in diabetes. (United States)

    Rosei, Enrico Agabiti; Rizzoni, Damiano


    The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin-angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure.

  9. The Case of Small Retailers


    World Bank Group; World Economic Forum


    This report aims to deepen the understanding of barriers to and incentives for the acceptance and use of electronic payments, from the perspective of micro, small and medium retailers (merchants). Developing and accelerating acceptance of electronic payments by these merchants is essential to expanding financial access. A basic transaction account for payments and deposits is considered an...

  10. Modeling Interactions in Small Groups (United States)

    Heise, David R.


    A new theory of interaction within small groups posits that group members initiate actions when tension mounts between the affective meanings of their situational identities and impressions produced by recent events. Actors choose partners and behaviors so as to reduce the tensions. A computer model based on this theory, incorporating reciprocal…

  11. Economics : An emerging small world

    NARCIS (Netherlands)

    Goyal, S; van der Leij, MJ; Moraga-Gonzalez, JL


    We study the evolution of social distance among economists over the period 1970-2000. While the number of economists has more than doubled, the distance between them, which was already small, has declined significantly. The key to understanding the short average distances is the observation that eco

  12. Small store presence in Japan

    NARCIS (Netherlands)

    M.A. Carree (Martin); J.C.A. Potjes; A.R. Thurik (Roy)


    textabstractThe determinants of the development of small store presence in Japan are investigated using a fixed effects multinomial logit market share model. Large stores tend to have higher market shares in shop-types with increasing shares in consumer expenditures, increasing inventory turnover, a

  13. Chaperone-mediated specificity in Ras and Rap signaling. (United States)

    Azoulay-Alfaguter, Inbar; Strazza, Marianne; Mor, Adam


    Ras and Rap proteins are closely related small guanosine triphosphatase (GTPases) that share similar effector-binding domains but operate in a very different signaling networks; Ras has a dominant role in cell proliferation, while Rap mediates cell adhesion. Ras and Rap proteins are regulated by several shared processes such as post-translational modification, phosphorylation, activation by guanine exchange factors and inhibition by GTPase-activating proteins. Sub-cellular localization and trafficking of these proteins to and from the plasma membrane are additional important regulatory features that impact small GTPases function. Despite its importance, the trafficking mechanisms of Ras and Rap proteins are not completely understood. Chaperone proteins play a critical role in trafficking of GTPases and will be the focus of the discussion in this work. We will review several aspects of chaperone biology focusing on specificity toward particular members of the small GTPase family. Understanding this specificity should provide key insights into drug development targeting individual small GTPases.

  14. Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications (United States)

    Ruscito, Annamaria; DeRosa, Maria


    Aptamers are single-stranded, synthetic oligonucleotides that fold into 3-dimensional shapes capable of binding non-covalently with high affinity and specificity to a target molecule. They are generated via an in vitro process known as the Systematic Evolution of Ligands by EXponential enrichment, from which candidates are screened and characterized, and then applied in aptamer-based biosensors for target detection. Aptamers for small molecule targets such as toxins, antibiotics, molecular markers, drugs, and heavy metals will be the focus of this review. Their accurate detection is ultimately needed for the protection and wellbeing of humans and animals. However, issues such as the drastic difference in size of the aptamer and small molecule make it challenging to select, characterize, and apply aptamers for the detection of small molecules. Thus, recent (since 2012) notable advances in small molecule aptamers, which have overcome some of these challenges, are presented here, while defining challenges that still exist are discussed

  15. Size variation in small-bodied humans from palau, micronesia.

    Directory of Open Access Journals (Sweden)

    Andrew Gallagher

    Full Text Available BACKGROUND: Recent discoveries on Palau are claimed to represent the remains of small-bodied humans that may display evidence insular size reduction. This claim has yet to be statistically validated METHODOLOGY/PRINCIPAL FINDINGS: Published postcranial specimens (n = 16 from Palau were assessed relative to recent small-bodied comparative samples. Resampling statistical approaches were employed to test specific hypotheses relating to body size in the Palau sample. Results confirm that the Palau postcranial sample is indisputably small-bodied. CONCLUSIONS/SIGNIFICANCE: A single, homogenous body size morph is represented in early prehistoric postcrania from Palau. Small body size in early Palauans is an ancestral characteristic and was likely not a consequence of in-situ size reduction. Specimens from Palau have little bearing upon hypothesised insular size reduction in the ancestral lineage of Homo floresiensis.

  16. Small-amplitude viscous motion on arbitrary potential flows (United States)

    Goldstein, M. E.


    This paper is concerned with small-amplitude, unsteady, vortical and entropic motion imposed on steady potential flows. It is restricted to the case where the spatial scale of the unsteady motion is small compared to that of the mean flow. Under such conditions, the unsteady motion may be influenced by viscosity even if the mean flow is not. An exact high-frequency (small-wavelength) solution is obtained for the small-amplitude viscous motion imposed on a steady potential flow. It generalizes the one obtained by Pearson (1959) for the homogeneous-strain case to the case of quasi-homogeneous strain. This result is used to study the effect of viscosity on rapidly distorted turbulent flows. Specific numerical results are given for a turbulent flow near a two-dimensional stagnation point.

  17. Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications

    Directory of Open Access Journals (Sweden)

    Annamaria eRuscito


    Full Text Available Aptamers are single-stranded, synthetic oligonucleotides that fold into 3-dimensional shapes capable of binding non-covalently with high affinity and specificity to a target molecule. They are generated via an in vitro process known as the Systematic Evolution of Ligands by EXponential enrichment, from which candidates are screened and characterized, and then applied in aptamer-based biosensors for target detection. Aptamers for small molecule targets such as toxins, antibiotics, molecular markers, drugs, and heavy metals will be the focus of this review. Their accurate detection is ultimately needed for the protection and wellbeing of humans and animals. However, issues such as the drastic difference in size of the aptamer and small molecule make it challenging to select, characterize, and apply aptamers for the detection of small molecules. Thus, recent (since 2012 notable advances in small molecule aptamers, which have overcome some of these challenges, are presented here, while defining challenges that still exist are discussed

  18. Environmental flows in the context of small reservoirs in Ghana (United States)

    Gao, Y.; Kirshen, P.; Vogel, R.; Walker, P.


    Modification of rivers by dams reduces the magnitude and frequency of floods, and impacts the entire flow regime. In many cases, these modifications have adversely affected the ecological and hydrological integrity of the watershed as well as impacting food security and livelihood choices of the local community. There is now an increasing consensus that modification to river flows needs to be balanced with maintenance of essential water-dependent ecological services. Many small multi-purpose reservoirs have been built in West Africa, where rainfall is highly variable, and droughts and flash floods are frequent. These small reservoirs are an important source of water for domestic use, livestock watering, small-scale irrigation and other beneficial uses in rural communities. The small reservoirs are hydrologically linked by their associated stream network. The reservoirs alter the hydrology of the streams and the groundwater resources within the region. When an individual reservoir is considered, alteration to the entire watershed is usually not significant. However, when considered as a system, together the small reservoirs store a significant quantity of water and influence downstream flows. The small reservoirs have rarely been considered as a system, thus little consideration has been given to their collective impact on the natural environment and livelihoods of the local population in the long term. Furthermore, the impact is difficult to quantify given the diffuse nature of the small reservoirs. Therefore, a comprehensive environmental flow assessment is needed to investigate the effect of the small reservoirs as a system on the watershed, and appropriate water policy should be formulated to implement the finding from the assessment. Our project is specifically aimed at addressing this topic. We will present a case study conducted in the Upper East Region of Ghana and will discuss the findings on the hydrological, ecological and socio-economic implications of

  19. Small Bodies, Big Discoveries: NASA's Small Bodies Education Program (United States)

    Mayo, L.; Erickson, K. J.


    2014 is turning out to be a watershed year for celestial events involving the solar system's unsung heroes, small bodies. This includes the close flyby of comet C/2013 A1 / Siding Spring with Mars in October and the historic Rosetta mission with its Philae lander to comet 67P/Churyumov-Gerasimenko. Beyond 2014, the much anticipated 2015 Pluto flyby by New Horizons and the February Dawn Mission arrival at Ceres will take center stage. To deliver the excitement and wonder of our solar system's small bodies to worldwide audiences, NASA's JPL and GSFC education teams in partnership with NASA EDGE will reach out to the public through multiple venues including broadcast media, social media, science and math focused educational activities, observing challenges, interactive visualization tools like "Eyes on the Solar System" and more. This talk will highlight NASA's focused education effort to engage the public in small bodies mission science and the role these objects play in our understanding of the formation and evolution of the solar system.

  20. Small is beautiful: models of small neuronal networks. (United States)

    Lamb, Damon G; Calabrese, Ronald L


    Modeling has contributed a great deal to our understanding of how individual neurons and neuronal networks function. In this review, we focus on models of the small neuronal networks of invertebrates, especially rhythmically active CPG networks. Models have elucidated many aspects of these networks, from identifying key interacting membrane properties to pointing out gaps in our understanding, for example missing neurons. Even the complex CPGs of vertebrates, such as those that underlie respiration, have been reduced to small network models to great effect. Modeling of these networks spans from simplified models, which are amenable to mathematical analyses, to very complicated biophysical models. Some researchers have now adopted a population approach, where they generate and analyze many related models that differ in a few to several judiciously chosen free parameters; often these parameters show variability across animals and thus justify the approach. Models of small neuronal networks will continue to expand and refine our understanding of how neuronal networks in all animals program motor output, process sensory information and learn.